Background: The COVID-19 pandemic has presented numerous challenges to global healthcare system and emerging evidence suggests a potential link between COVID-19 treatment, specifically steroid therapy, and the development of avascular necrosis (AVN) of the hip. This review aims to provide a comprehensive overview of recent studies and case reports investigating the relationship between COVID-19, corticosteroid therapy, and the development of AVN. Understanding the nuances of AVN in the context of COVID-19 is crucial for healthcare professionals to navigate treatment decisions and mitigate potential complications. Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used in the systematic review until September 1st, 2023. The full-texts of the remaining twenty-three (n=23) articles were independently reviewed by the authors of this review.  Conclusions: The association between steroid therapy for COVID-19 and the development of hip AVN is a noteworthy concern even though, no relationship is evident between the duration of treatment, cumulative dosage of medication, maximum daily dosage received, and the presence of AVN. Further research with larger cohorts and long-term follow-up is needed to better understand the causative relationship and optimal management strategies for hip AVN in the context of COVID-19 and steroid therapy

Background and Objectives: The healing of bone defects is a serious challenge worldwide. One branch of dentistry deals with bone defects. capsaicin has anti-inflammatory, anti-oxidative and cholesterol-reducing effects. The aim of this study is to evaluate the effects of systemic capsaicin administered at different doses on bone healing. Materials and Methods: A total of 32 male wistar rats was used, their weight varying between 250 and 300 g. The rats were randomly divided into four groups of eight rats each. The analyses served to evaluate the effect on healing of different doses of capsaicin and grafts. A significant increase was observed in the number of osteoblasts in the capsaicin-applied groups compared to the control group. Conclusions: As a result of the analyses, positive effects on bone healing were observed when capsaicin 0.25 mg/kg and 0.50 mg/kg was administered intraperitoneally. However, more studies are needed for more accurate information.

The impact of obesity upon bone metabolism is controversial since both negative and positive effects have been reported. Bone remodeling is modulated by the central nervous system through cytokines, hormones and neuromodulators. The present study aimed to evaluate the effects evoked by bilateral retroperitoneal white adipose tissue (rWAT) denervation (Dnx) upon bone mineral metabolism and remodeling in an experimental model of obesity in rats. Male Wistar rats were fed during 18 weeks with high-fat diet (HFD) or standard diet (SD) as controls, and rWAT Dnx or Sham surgery was performed at the 14th week. Biochemical and hormonal parameters, bone histo-morphometry, rWAT and hypothalamus protein and gene expression were analyzed. HFD group presented decreased bone formation parameters, increased serum and bone leptin and FGF23, increased serum and hypothalamic neuropeptide Y (NPY) and decreased serum 1,25-dihydroxyvitamin D3 and PTH. After rWAT Dnx, bone markers and histomorphometry showed restoration of bone formation, serum and hypothalamic NPY decreased, without altera-tion in leptin levels. The present study showed that the denervation of rWAT improved bone formation in obese rats mediated by a preferential reduction in neurohormonal actions of NPY, emphasizing the relevance of the adipose tissue-brain-bone axis in the control of bone metabolism in obesity.

Medicinal plants for bone grafts are promising because they are free from infecting microorganisms and biocompatible. We report a novel study evaluating osteoregeneration of bone grafts from extracts of Alternanthera brasiliana and Fridericia platyphylla after bone injury induced by radius fracture in rats. Grafts were obtained using 2% chitosan gel and 0.5% hydroalcoholic extract. The rats were randomly divided into four experimental groups (N= 12): Negative control (NC) - Chitosan gel; Positive control (PC) - bovine mineral bone graft (Lumina Bone®, fine powder 0.5); F. platyphylla Graft (FRID) - 0.5% bone graft; A. brasiliana Graft (ABRA) - 0.5% bone graft. The animals were evaluated for three periods, 30, 60, and 90 days after fracture induction. Bone alkaline phosphatase (BSAP) and radiographic and histological evaluations were followed. After 90 days, there was an increase in BSAP for the ABRA group on the newly formed bone matrix but not for FRID, indicating the presence of active osteoblasts. Additionally, mature bone tissue and bone remodeling were observed, and a conspicuous presence of type I collagen for both FRID and ABRA. We demonstrated that FRID and ABRA grafts produced early bone neoformation. New perspectives for these species as a graft are suggested.

Objectives Bone fractures are very common diseases, which can be caused by impact injuries or physiological disorders. Thus, the present review aimed to study the use of medicinal plants in the healing mechanism of bone fractures. Evidence acquisition Through research in the PubMed, Google Academic, and Scielo databases, this article reviews 11 ethnopharmacological studies and 34 preclinical studies on the biological actions of different plants in bone fracture healing mechanism. Results Indian tribes have highlighted in the plants ethnopharmacological study for various diseases, including bone fractures. However, despite the large citations of traditional use, technical-scientific studies are still scarce in the literature. Chenopodium ambrosioides, Piper sarmentosum, quadrangular Cissus, Ricinus communis and Radix salvia miltiorrhiza plants were the most studied in the literature regarding their osteogenic, angiogenic, anti-inflammatory and remodeling effects, acting on bone receptors, stimulating bone metabolism, increasing minerals uptake, and assisting in free radicals breakdown. Conclusion Thus, the medicinal plants use is promising in the field of bone regeneration, as well as being alternative when conventional therapies are unfeasible, increasing herbal medicines demand and popularity.

In orthopedics, bone drilling is a crucial part of a surgical method commonly carried out for internal fixation in bone fracture treatment. The primary purpose of bone drilling is the creation of holes for screw insertion to immobilize fractured parts. The bone drilling task depends on the orthopedist and surgeon’s high level of skill and experience. This paper aimed to provide a summary of previously published review studies in the field of bone drilling. This review paper also presents a comprehensive review of the application of machine learning for bone drilling and as a future direction for the automation system. This review can also help medical surgeons and bone drillers understand the latest improvements through parameter selection and optimization strategies to reduce bone damage in bone drilling procedures. Apart from the review study, bone drilling vibration data collected in the University laboratory experiment is also presented in this study. The vibration data consist of three different layers of femur cow bone which are processed and classified using several machine learning methods. LSTM is, used in the bone drilling classification study to prove that the layers of the bone drilling are associated with the vibration signal and can be classified and predicted using the machine learning method.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p<0.05; p<0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p<0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

The occurrence of bone-related disorders and diseases has increased dramatically in recent years around the world. Demineralized bone matrix (DBM) has been widely used as a bone implant due to its osteoinduction and bioactivity. However, the use of DBM is limited because it is a particulate material, which makes it difficult to manipulate and implant with precision, in addition, these particles are susceptible to migrate to other sites. To address this situation, DBM is commonly incorporated into a variety of carriers. An injectable scaffold has advantages over bone grafts or preformed scaffolds, such as the ability to flow and fill the bone defect. The aim of this research is to develop a DBM carrier with such viscoelastic properties to obtain an injectable bone substitute (IBS). The DBM carrier developed consisted of a PVA/glycerol network cross-linked with borax and reinforced with CaCO3 as a pH neutralizer, porosity generator, and source of Ca. The physicochemical properties were determined by the injectability test, FTIR, SEM, and TGA. Porosity, degradation, bioactivity, possible cytotoxic effect, and proliferation in osteoblasts were also determined. The results show that the developed material has great potential to be used in bone tissue regeneration

Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts), the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoportegerin, osterix, RANKL, Runx2) and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others presented a beneficial and stimulating effect in the bone regeneration process due to pro-estrogenic activity, antioxidant and anti-inflammatory effects and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone related pathologies envisaged by incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.

Background: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. Methods: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations at one side of the mandible and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, the xenograft block was adapted to the defect and fixed with an implant (inlay group). Results: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close at the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ±9.3%) compared to the onlay (10.4 ±7.4%) groups (p=0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ±1.05% at the onlay group and 0.78 ±0.71% at the inlay group (p=0.603). Conclusion: The inlay grafts exhibited a higher new bone percentage than the onlay grafts possibly due to the defect conformation that presented more sources for bone formation. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in growth of bone on the graft trabeculae toward the most superior regions in both groups, and in the closure of the coronal entrance of the defects in the inlay group.

Background: The conformation of the recipient site for an inlay graft presents an increased contact with the parent bone compared to the onlay graft. This might favor bone growth within the inlay compared to the onlay grafts. Hence, the objective of this study was to compare bone incorporation and remodeling process of xenogeneic en bloc grafts, placed using two bone grafting techniques, i.e., onlay vs. inlay. Methods: In this prospective, randomized, split-mouth study (test and control sides in the same animal), two bone grafting techniques were comparatively evaluated on the lateral aspect of the rabbit mandibles. One side was prepared with perforations (onlay site), whereas the other side was prepared with trephines and drills to obtain a wide (7 mm) standardized recipient site (inlay site). A xenogeneic bone block was fixed in the center with a titanium screw in both sides of the mandible and covered with a collagen membrane. Two healing periods were applied in the study: 2 and 10 weeks of healing. Results: after 2 weeks of healing, the mean percentage of new bone was 10.4% and 23.3% at the onlay and inlay grafts, respectively (p=0.022). After 10 weeks of healing, new bone increased to 13.2% and 25.4%, respectively (p=0.080). In this period of healing, the inlay grafts presented new bone percentage >20% in all regions examined while the onlay graft presented a lower percentage in the most external regions of the graft. Conclusion: The percentage of new bone increased faster and was higher in the inlay compared to the onlay grafts. The composition of the grafts allowed new bone to reach the most peripheral regions in both graft groups, even though it was higher in the inlay group. A marginal closure of the defects by newly formed bone was observed in the inlay group.

AbstractCadaver bone is possibly the most common transplant material used today. Common types of cadaver bone transplants are freeze-dried bone allografts and xenografts. Studies have shown that mineralized freeze-dried bone allografts have the same percentage of retained bone graft particles at different time points, indicating that these materials are never resorbed. However, it is commonly accepted by clinicians that these materials are resorbed and convert the graft site into normal bone. This histologic study was undertaken to determine the fate of mineralized freeze-dried bone allograft particles grafted into human extraction sockets. Materials and Methods:This study is a photographic, radiologic, and histological analysis of mineralized freeze-dried bone allograft healing in human sockets after mineralization at different time points. The mineralized freeze-dried bone allografts used for evaluation in this study were particulate bone graft materials in maxillary or mandibular extraction sockets. Patient selection was random, based on the following time periods: 6 months, 2 years, 5 years, 7 years, 10 years and 15 years. No block bone grafts were evaluated. Results:No resorption of cadaver bone graft particles was found at any time point. No osteoclasts were found in any of the histology at any time point. At different time points from 6 months through 15 years, mineralized freeze-dried bone allograft particles were found to be exfoliated out of the alveolar crest as a result of the formation of a hypervascular zone surrounding the grafted site. The embedded graft particles remain embedded in sclerotic bone until the particles reach the alveolar crest at which time the sclerotic bone and graft particles break up and are released into the gingiva. All histologic samples from 6 months to 15 years contained residual graft particles. The sclerotic bone formed around graft particles did not integrate to the graft particles or the implant surface. Conclusions:Mineralized freeze-dried bone allograft particles are not resorbed after mineralization. A hypervascular zone forms around the grafted site and exfoliates the bone graft particles into the gingiva. The mineralization process produces sclerotic bone which never remodels into normal bone. Sclerotic bone covers but does not integrate to the retained bone graft particles or implant surface resulting in a weakened structure with an increased likelihood of bone failure and implant loss.

Recent research efforts in bone tissue engineering have been primarily directed towards manufacture-viable synthesis of biomaterials that can significantly enhance the biocompatibilities and osteogenic capabilities on the new biomaterials. This paper presents a straightforward, cost-effective, optimized, and well-controlled hydrothermal synthesis of Nb-doped potassium titanate nanofibers in high-purity. Characterization data revealed that the Nb-doping potassium titanate maintained the crystal structure, showing great promise for applications in bone tissue engineering.

Objectives. To compare the audiological benefits of a non-implantable wearing option of a bone conduction (BC) implant mounted on an arch (SoundArc) to traditional BC hearing aids (HA) mounted on eyeglasses (BCHA) in patients with moderate to severe conductive or mixed hearing loss. Methods: A preliminary cross-sectional observational prospective cohort study was conducted at a Tertiary Audiological Department, University Hospital. Fourteen adults with conductive or mixed hearing loss (PTA at 0.5-1-2-4 KHz = 67 ± 15 dB HL) had been wearing conventional BCHA on eyeglasses for at least 3 years, and refused the surgical implantation of a BC hearing implant (BCHI). Unaided and aided pure-tone AC and BC thresholds and speech test in quiet and in noise were recorded at baseline and in two different settings: with a BCHI mounted on SoundArc®, and with their own BCHA with two couplers, mounted on eyeglasses. International Inventory for Hearing Aids [IOI – HA], the Hearing Handicap Inventory [HHIA/E], Speech, Spatial, Qualities of Hearing Scale [SSQ], a 10-scores visuo-analogic scale [VAS], and Fatigue impact scale [FIS] score were asked in both conditions. Results: a statistical significative functional gain was observed for both settings. (p=.0001) Better speech perception performances in quiet and in noise were observed with SoundArc compared to their conventional BCHA on eyeglasses (word repetition score in noise improvement of +19.3 at SNR +10 dB, p=.002; + 12.1 at SNR 0 dB, p=.006; and +11.4 at SNR -10 dB, p=.002) No significant differences were found in IOI–HA, FIS, and HHIA/E scores, while significative better SSQ scores in all domains were reported for SoundArc. (p=.0038) Conclusions: Although patients were accustomed to their BCHA on eyeglasses, the non-implanted wearable option of the BCHI proved to be a viable alternative in adult patients with conductive or mixed hearing loss unable to receive or refusing BCHI surgery.

Salmon aquaculture generates a substantial volume of waste material, offering potential for biomaterial production. This industry produces significant waste, which can be repurposed for various biological applications, particularly in biomaterial production for tissue engineering with pertinent applications in osteo-conduction, osteo-induction, and clinical/surgical bone regeneration and repair. The process involves a standardized pre-treatment stage aimed at minimizing biological waste content. Subsequently, the treatment stage, contingent on the chosen methodology, facilitates the removal of proteins, lipids, molecules, and other compounds, leaving the mineral phase as a valuable substrate. The selection of the optimal method, whether alkaline hydrolysis, calcination, or NaOH hydrolysis, for obtaining this substrate necessitates thorough examination through chemical, physical, and biological assessments, including Raman Spectroscopy and X-Ray Diffraction. This study aims to identify the most efficient laboratory process for biofunctional nano-sized hydroxyapatite mineral production derived from Chilean salmon fish backbone waste.

Critical illness has been recognized to acutely influence bone metabolism and, consequently, bone mineral density. The main purpose of this study was to describe bone metabolism changes in adult survivors of critical illness in the attempt to correlate changes with severity scores. It is an open, prospective, observational, monocentric study on patients admitted to the ICU was conducted, evaluating bone metabolism at baseline (within 72 hours of ICU admission), 6 months, and 12 months. Fifty-nine patients admitted to the ICU (63% males), mean age 58 ± 16 years, were enrolled. Of these, 20 patients (34%) completed the one-year follow up. At baseline, bone resorption showed an increase, which was maintained at 6 months, with normalization at 12 months. Patients showed, in a majority of cases, hypovitaminosis D with hyperparathyroidism at baseline with subsequent normalization. A trend towards a correlation was described between severity scores and serum 25(OH) vitamin D and bone turnover marker levels. These results contribute to the confirmation of a positive association between critical illness requiring ICU and bone metabolism changes. This study poses the bases for further studies to evaluate bone health in ICU patients.

Physical activity is widely recognized as a biotherapy by WHO in the fight and prevention of bone diseases such as osteoporosis. It reduces the risk of disabling fractures associated with many comorbidities, and whose repair is a major public health and economic issue. Bone tissue is a dynamic supportive tissue that reshapes itself according to the mechanical stresses to which it is exposed. Physical exercise is recognized as a key factor for bone health. However, the effects of exercise on bone quality depend on exercise protocols, duration, intensity and frequency. Today, the effects of different exercise modalities on capillary bone vascularization, bone blood flow and bone angiogenesis remain poorly understood and unclear. As vascularization is an integral part of bone repair process, the analysis of the preventive and/or curative effects of physical exercise is currently very undeveloped. Angiogenesis-osteogenesis coupling may constitute a new way for understanding the role of physical activity, especially in fracturing or in the integration of bone biomaterials. Thus, this review aims to clarify the link between physical activities, vascularization and bone repair.

In the present study, the efficiency of a biomimetic approach by coating demineralized bone matrix (DBM) amorphous calcium phosphate (DBM+CaP), including its combination with serum albumin (DBM+CaP+BSA), was investigated. The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into DPCD with a characteristic plate shape and particle size of 5–35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/ml in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM+CaP and DBM+CaP+BSA, but more pronounced effects for DBM+CaP+BSA. In addition, for the DBM+CaP+BSA samples, a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite have been achieved.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p<0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

It was assumed that only autogenous bone had appropriate osteoconductive and osteoindutive properties for bone regeneration, but this assumption has been challenged. Many studies have shown that synthetic biomaterials must be considered as the best choice for bone guided regeneration. The objective of this work is to compare the performances of nano-hydroxyapatite/β-Tricalcium phosphate (n-HA/β-TCP) composite and autogenous bone graft in bone regeneration applications. Th composite was characterized by scanning electron microscopy (SEM) and used as an allograft in bone defects made in adult Wistar rats. The bone defects in the dorsal cranium were grafted with autogenous bone on one side and the n-HA/β-TCP composite on the other. Histomorphometry evaluation by different staining methods (Goldner trichrome, PAS, Sirius red) and TRAP histochemistry were performed. The immunohistomorphometries to OPN, Cathepsin-K, TRAP, Acid phosphatase, VEGF, NFκ-β, MMP-2, MMP-9, and TGF-β were carried out. The RT-PCR method to RANK-L, Osteocalcine, Alcaline Phosphatase, Osterix, and Runx2 were conducted as well. The results showed that all morphometric evaluations on the different staining methods, histochemistry and immunohistochemistry, VEGF and NFκ-β, were higher on the n-HA/β-TCP composite group than in the autogenous bone graft group. The RT-PCR markers were higher in the autogenous bone group than on the n-HA/β-TCP composite group. The n-HA/β-TCP composite exhibited enhanced cell-matrix interactions in bone remodeling, higher adhesion, proliferation, and differentiation, and increased vascularization. These results suggests that the n-HA/β-TCP composite induces faster bone formation than autogenous bone.

Bone drilling is a common procedure used to create pilot holes for inserting screws to secure implants for fracture fixation. However, dis process can increase bone temperature, teh excessive heat can lead to cell death and thermal osteonecrosis, potentially causing early fixation failure or complications. We conducted a three-dimensional dynamic elastoplastic finite element model to evaluate teh propagation and distribution of heat during bone drilling and assess teh thermally TEMPeffected zone (TAZ) dat may lead to thermal necrosis. dis model investigates teh parameters influencing bone temperature during bone drilling, including drill diameter, rotational speed, feed force, and predrilled hole. Teh results indicate dat our FE model is sufficiently accurate in predicting teh temperature rise TEMPeffect during bone drilling. Teh maximum temperature decreases exponentially wif radial distance. When teh feed forces are 40 and 60 N, teh maximum temperature does not exceed 45 °C. However, wif feed forces of 10 and 20 N, both teh maximum temperature exceeds 45 °C wifin a radial distance of 0.2 mm, indicating a high-risk zone for potential thermal osteonecrosis. Wif teh two-stage drilling procedure, where a 2.5 mm pilot hole is pre-drilled, teh maximum temperature can be reduced by 14 °C. dis suggests dat higher feed force and rotational speed and/or using a two-stage drilling process could mitigate bone temperature elevation and reduce teh risk of thermal osteonecrosis during bone drilling.

Our results demonstrated that SWT stimulates osteoblastogenesis and increase the cell number of osteoblasts, suggesting positive regulatory effects on osteoblast differentiation. However, the effect of SWT on bone formation need further examination, since the expression of alp gene is downregulated. On the other hand, SWT appears to negatively regulate osteoclast differentiation and bone resorption, as number of osteoclasts and the expression of critical bone resorptive genes are all downregulated. Collectively, SWT might change the equilibrium of bone remodeling and increase the bone mass. Our data provided supportive evidences that this medicine formulation can be applied to treat osteoporosis or bone destructive diseases.

Synthetic bone made of calcium phosphate is widely used for the clinical treatment of bone defects caused by trauma and bone tumors. Although synthetic bone is easy to use, its effects are only partial depending on the size and location of the bone defect, and there are many treatment options other than the use of synthetic bone. Various biodegradable polymers that are being considered for use as scaffolds for regenerative medicine are also being considered for use as synthetic bones; however, commercial synthetic bone products with performance comparable to that of calcium phosphate bioceramics have not yet been clinically applied. This review introduces the practice of bone regeneration therapy with synthetic bone and recent research on bone regeneration therapy with biodegradable polymers.

Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research on using shell nacre as cement with improved physico-chemical properties. To address this, the current study aimed to develop a chemical curable com-posite shell nacre cement (SNC) using shell nacre powder and an organically modified ceramic resin shell nacre containing ladder-structured siloxane methacrylate (SNLSM). Different amounts of shell nacre (24, 48, and 72 weight(wt)%) were added to the SNLSM resin matrix and the effect on the physicochemical properties of the cement was studied. The composite shell nacre cement SNC 72 containing 72 wt% shell nacre exhibited significantly higher mechanical properties (com-pressive strength >100 MPa, flexural strength > 35 MPa) and low linear polymerization shrinkage (0.4%) than other compositions. SNC 72 was radiopaque and the exotherm generated during the curing of the cement was minimal. Direct contact of cured SNC 72 with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the results of the study proved that the composite SNC 72 would be a promising candidate for bone defect management.

The frequent occurrence of rib fractures in slaughtered lambs results in significant economic loss to producers and processors in South Australia and raises concerns about the welfare of the animals. The prevalence of rib fractures became evident through the Enhanced Abattoir Surveillance (EAS) program introduced in 2007. The present study aimed to investigate the association between rib fracture prevalence in lambs at slaughter and their nutrition and management on the farm of origin. The slaughter of 30,055 lambs from 60 farms was monitored at a South Australian abattoir in November 2016. Rib fracture prevalence was 4% (range 0 - 18% per consignment), with all consignments of more than 240 lambs having at least one with fractured ribs. Traceback investigation on 56 of the 60 farms suggests that rib fractures most probably occur during routine husbandry procedures and, based on soil mineral analysis, are associated with calcium inadequacy. There was substantial variation between lines of lambs from different farms, and factors contributing to the differences included line size, region, and soil characteristics, including available calcium. There is a need to modify sheep husbandry and management practices to improve sheep welfare and reduce the cost of rib fractures to the sheep industry.

In the pursuit of better treatments, the concept of a chemically-active material, responding to local conditions by causing reactions, or reacting to produce substances that are deemed beneficial, seems laudable. Ultimately, the goal appears to be to recruit natural biological processes such that a natural ‘repair’ is effected. This goal seems to be the reason for prefixing “bio-“ to many terms with a view to advertising the desire, yet without presenting evidence that it has occurred, or indeed that it is capable of occurring, relying instead on non-biological processes to justify the claims. The dogma is such that all work where local ‘responsive’ chemistry is involved must receive the label “bioactive” to legitimize and promote. Nevertheless, the primary evidence adduced is flawed, and the claim must fail. A rethink to restore scientific sense and confidence in the endeavour is essential if real progress is to be made.

Background: Vitamin D is essential for bone health, influencing bone mineral density (BMD) and the prevention of bone-related disorders. Despite its importance, Vitamin D deficiency remains prevalent among young adults, raising concerns about its impact on skeletal health. Objective: This review aims to summarize the current understanding of Vitamin D's role in bone health, focusing on its effects on BMD in young adults, and to identify gaps in the existing literature. Methods: A comprehensive narrative review of recent studies and guidelines was conducted, covering Vitamin D synthesis, its impact on bone health, dietary recommendations, and public health implications. Data were sourced from PubMed, Google Scholar, and relevant clinical guidelines.

Background: Despite the fact that bone reconstructive surgeries are widely practiced worldwide, the search for an ideal bone replacement matetrial is still an open issue. We aimed to provide an overview of the current status of research and developments in this field with a focus on sapphire materials; Methods: A literature search and review was conducted using the PubMed, Scopus, and Embase databases. We searched for literature using the following keywords: bone implants; biocompatible materials; bone replacement material; sapphire implants; Results: Sapphire has a unique combination of mechanical, physical and chemical characteristics thanks to wich it has an excelent biocompatability and biointegrity.Unlike other materials it is incredibly strong and has a high endurance. The successful experience of using this material in medical instrument engineering, dentistry and cardiac surgery shows its benefits; Conclusions: We consider that sapphire is a perspective material for bone replacement implants and researchers should look in this direction.

This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers, in order to offer practical information for interpretation of nuclear images to physicians involved in the care of patients with this ATTR-CA.

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, where it not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying the specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined osteoimmunology. Specifically, we have comprehensively elaborated on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis lead to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Dental implants provide a predictable treatment option for partial and complete edentulism via the placement of fixed permanent artificial root to support prosthetic dental crowns. Despite the high survival rates, long-term implant failures are still reported leading to implant removal and additional financial and health burdens. While extrinsic factors that improve survival rate of implants have been well explored, the impact of genetic factors on this matter is poorly understood. A systematic review and meta-analysis study was conducted to determine whether genetic factors contribute to increase the risk of dental implant failure. A comprehensive search for peer-reviewed articles on dental implants and genetics was performed using various literature database libraries. The study design was conducted according to PRISMA guidelines, and the obtained records were registered in PROSPERO database. According to the exclusion/inclusion criteria, 11 studies were eligible for this study out of 808 articles. The meta-analysis of the combined association studies of DNA variations and dental implants did not indicate an increase risk for implant failure due to DNA variations in IL-1B, IL-10 and TNF-α. This study emphasizes the need for larger randomized controlled clinical trails to inform clinicians and patients about the role of genetic factors on dental implant survival and success rate in healthy and compromised patients.

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D scaffolds with ideal mechanical and biological properties remains an unattained challenge. In this work, a novel approach is explored to produce synthetic bone grafts mimicking the complex bone structure using additive manufacturing. For the first time, scaffolds were produced, using an extrusion technique, composed of a thermoplastic polymer, polycaprolactone (PCL), hydroxyapatite nanoparticles (HANp), and polyethylene glycol diacrylate (PEGDA). These scaffolds were further compared with two groups of scaffolds: one composed of PCL and another of PCL and HANp. After production, optimisation and characterisation of these scaffolds, an in vitro evaluation was performed using human dental pulp stem/stromal cells (hDPSCs). Through the findings it was possible to conclude that PEGDA scaffolds were successfully produced presenting networks of interconnected channels, presenting hydrophilic properties (15.15 4.06°), adequate mechanical performance (10.41MPa 0.934), and allowing a cell viability significantly superior to the other groups analysed. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes.

Steroid hormone production by adrenal cortex, gonads and placenta (so called glandular steroidogenesis) is responsible for the endocrine control of the body’s homeostasis and organized by a feedback regulatory mechanism based on the hypothalamus-pituitary-steroidogenic gland axis. On the other hand, recently discovered extraglandular steroidogenesis occurring locally in different tissues is rather linked to paracrine or autocrine signaling and it is independent of the control by the hypothalamus and pituitary. Bone cells, such as bone-forming osteoblast, osteoblast-derived osteocytes and bone-resorbing osteoclasts respond to steroid hormones produced by both glandular and extraglandular steroidogenesis. Recently, new techniques to identify steroid hormones as well as synthetic steroids and steroidogenesis inhibitors have been introduced, which greatly empowered steroid hormone research. Based on recent literature and new advances in the field, here we review the local role of steroid hormones in regulating bone homeostasis and skeletal lesion formation. The novel idea of extraglandular steroidogenesis occurring within the skeletal system raises the possibility of the development of new therapies for the treatment of bone diseases.

Introduction The placement of implants is often hindered by a severely atrophic mandibular edentulous ridge. A sufficient volume of bone graft is crucial for successful implant restoration. The required bone graft volume directly correlates with the deficiency present in the edentulous ridge. If the residual crestal bone height is so low that the distance between the crestal ridge and the inferior alveolar nerve is less than 2 mm, a significant bone augmentation procedure is necessary. This procedure must ensure the implants are surrounded by a sufficient margin of bone, aiming for a final height of more than 8 mm and a width of more than 7 mm. Achieving primary closure with adequate soft tissue is vital for the success of the bone graft procedure. The key to successful bone grafting lies in the effective management of the soft tissue covering. Case Report This case report details the treatment of a patient with severely atrophic edentulous ridges on both sides, addressed using Self Inflating Tissue Expanders (SITEs) to facilitate bone grafting and implant placement. Following soft tissue expansion, bone grafting and implant placement were successfully performed. The implants supported a fixed restoration, which remained stable and complication-free over a seven-year observation period. Conclusion The SITE (Self-Inflating Tissue Expander) proved effective in obtaining a substantial amount of bone graft needed for implant installation. A seven-year follow-up confirmed the implants were well-functioning with stable bone support, healthy soft tissue coverage, and adequate vestibular depth.

Background: Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects, however limitations include donor site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. Methods: Design of Experiments (DoE) was used to design 12 hydrogel bioinks of various Gelatin meth-acrylate/hydroxyapatite (GelMA/HA) concentrations. These bioinks were assessed for pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Two bioinks, the DoE designed maximal stiff-ness and the experimentally defined maximal stiffness vs. a literature based control were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. Results: DoE ANOVA analysis indicated that the augmented 3 level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% Gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% Gelatin. There were no significant differences in cell viability within hydrogels from day 2 to day 7 (p > 0.05). There was however a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with lower HA concentration (p < 0.05), showing that higher HA or print pressure may be cytotoxic within hydrogels. Conclusions: Extrusion-based 3DBP offers significant advantages for bone-tissue implants due to its high customizability. This study demonstrates it is possible to create printable bone-like grafts from GelMA and HA with increased HA levels, favorable mechanical properties (145kPa) and >80% cell viability.

In recent decades, porous scaffolds for bone tissue engineering (BTE) have gained significant attention. Considerable research efforts have been dedicated to investigating the impact of scaffold pore size on a diverse array of biological processes, including cell-scaffold interactions, substance transportation, and vascularization. However, the multi-scale hierarchical porosity, a key structural characteristic of natural bone, has rarely been replicated in BTE scaffolds due to the challenges of controlling the scaffold structure across multiple length scales. With the advancement of manufacturing technology, there has been increasing research on biomimetic multi-scale hierarchical materials, which are also gaining favor in the field of BTE. Therefore, there is an urgent need to review multi-scale hierarchical porous BTE scaffolds. This paper aims to review the role and fabrication methods of multi-scale porous BTE scaffolds at different length scales, the design and manufacturing of new BTE scaffolds for bone regeneration.

Antibiotic-loaded bone cements are widely used in orthopedic surgery. However, they present issues such as a short antibiotic release time and the antibiotic resistance. These challenges necessitate the development of novel antibacterial bone cements. Non-leaching bone cement containing antibacterial motifs represents a promising advancement in this direction. Antibacterial motifs are incorporated into the cement either covalently or non-covalently, and while they will not be released, they will still exhibit surface antibacterial activity. This review comprehensively examines the structure and antimicrobial activity of prevalent non-leaching antimicrobial bone cements. Additionally, it delves into the characteristics of current methods employed for detecting surface antimicrobial activity. Finally, the future research direction of non-leaching antibacterial bone cement is discussed, with a specific focus on innovative antibacterial motifs, the mechanisms underlying non-leaching antibacterial properties, and the potential synergies achievable by combining non-leaching antibacterial bone cement with traditional antibiotics.

The potential of sericin, a protein derived from silkworms, is explored in bone graft applications. Sericin's biocompatibility, hydrophilic nature, and cost-effectiveness make it a promising candidate for enhancing traditional graft materials. Its antioxidant, anti-inflammatory, and UV-resistant properties contribute to a healthier bone-healing environment, and its incorporation into 3D-printed grafts could lead to personalized medical solutions. However, despite these promising attributes, there are still gaps in our understanding. The precise mechanism through which sericin influences bone cell growth and healing is not fully understood, and more comprehensive clinical trials are needed to confirm its long-term biocompatibility in humans. Furthermore, the best methods for incorporating sericin into existing graft materials are still under investigation, and potential allergic reactions or immune responses to sericin need further study.

Bone Scan Index (BSI) is an image biomarker for quantification on bone metastasis of cancers. To compute BSI, not only the hotspots (metastasis) but also the bones have to be segmented. Most related researches focus on binary classification on bone scintigraphy: having metastasis or none. Rare studies focus on pixelwise segmentation. In this study we compare three advanced convolutional neural network (CNN) based models to explore the bone segmentation on dataset in house. The best model is Mask R-CNN, which reaches the precision, sensitivity and F1-score: 0.93, 0.87, 0.90 for prostate cancer patients and 0.92, 0.86, 0.88 for breast cancer patients, respectively. The results are the average of 10-fold cross-validation, which reveals the reliability for clinical use on bone segmentation.

Thermoplastic molded regenerated silk was proposed as structural material in tissue engineering applications, mainly for application in bone. The protocol allows to obtain a compact non-porous material with a compression modulus in the order of a Giga Pascal starting from silk fibroin by compressing a silk fibroin lyophilized sponge of powder in mold at temperature higher than the glass transition temperature (Tg). The main purpose of the produced resin was the osteofixation and other structural applications in which the lack of porosity was not an issue. In this work, we introduced the use of citric acid in the thermoplastic molding protocol of SF to obtain a porosity inside the structural material. In addition to the previously developed protocols the addition of citric acid allowed us to obtain a structural material. The CA powder during the compression acted as a template for the pore formation. In addition, the CA was able to effectively crosslink the SF chain improving the mechanical strength. This effect was proved both evaluating the compression modulus and by studying the spectra obtained by Fourier infrared spectroscopy (FTIR). This protocol may be applied in the near future to the production of a structural bone scaffold.

Purpose: to assess any differences on marginal bone loss between bone-level or tissue-level dental implants through a review of literature until September 2019. Materials and methods: MEDLINE, Embase and other database were searched by two independent authors. The search was limited to articles in English. Results: The search provided 1028 records and, after removing the duplicates through titles and abstracts screening, 45 full-text articles were assessed for eligibility. For qualitative analysis 20 articles were included, 17 articles of them for quantitative analysis. A total of 1161 patients (mean age 54,4 years) and 2933 implants were observed, 1427 (Tissue-level) and 1506 (Bone-level). The survival rate and the success rate were more than 90%, except for 2 studies with a success rate of 88% and 86.2%. No studies reported any differences between groups in term of success and survival rates. Three studies showed that BL-implants had statistically less marginal bone loss (P< 0.05). Only one study reported statistically less marginal bone loss in TL-implants (P< 0.05). In the most part of the studies, differences between implant types in marginal bone loss were not statistically significant. Conclusion: Despite to the peri-implant tissue around transmucosal implants has been reported to be inflammation-free because of the absence of bacterial infiltration in the micro-gap between the fixture and abutment, no clinical and radiological differences were highlighted between groups from the included studies after a variable period of follow-up ranged between 1 to 5 years.

The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR) procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show an optimal integration behaviour of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations of OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p<0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralisation), as well as providing additional space for new bone formation by rapid resorption.

Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the microorganism can occur after ingestion of contaminated food products. Small and large outbreaks of listeriosis have been described in the past. L. monocytogenes can cause a number of different clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. L. monocytogenes systemic infections can develop following tissue penetration across the gastrointestinal tract or to hematogenous spread to sterile sites, possibly evolving towards bacteremia. L. monocytogenes only rarely causes bone or joint infections, usually in the context of prosthetic material that can provide a site for bacterial seeding. We describe here the clinical findings of invasive listeriosis, mainly focusing on diagnosis, clinical management and treatment of bone and vertebral infections occurring in the context of invasive listeriosis.

Background: Bone metastases (BM) have a detrimental effect on survival for patients with solid cancers. Materials and methods: This systematic review respected the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results: When investigating OP as a risk factor for BM development, for breast cancer patients, some articles do not differentiate between intrinsic breast cancer subtypes. BMD does not seem to contribute in a significant manner when investigating Luminal A breast cancer. While researching breast cancer regardless of intrinsic subtype, untreated OP increases the risk of bone metastasis when compared to no OP group or treated OP group. In urological cancer cases, OP seems to predispose the patients to BM, especially early after diagnosis. Investigating risk factors for OP development in cancer patients resulted in the identification of 32 articles. Most articles identified risk factors for osteoporosis development in the context of breast cancer patients. Other commonly investigated solid cancers were prostate, other urological cancers, gynecological malignancies, and other less common subtypes of solid tumors. Discussion: While investigating OP as a risk factor for BM, it becomes clear that there is a high grade of heterogeneity in the behavior of each type of cancer in its dynamic concerning bone metastasis, and thus, OP might have different behaviors as a risk factor depending on the situation. Conclusion: There is a need for data regarding cancer subtypes that have not been explored concerning their interaction with the skeletal system in a low bone mineral density scenario.

Rhodiola rosea, a perennial herb from the Crassulaceae family, contains the bioactive compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key transcription factors such as runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone formation with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2–related factor 2 pathway. Salidroside's ability to counteract the negative effects of glucocorticoids on bone cells and prevent steroid-induced osteonecrosis, along with its anti-inflammatory properties, enhances its potential in treating conditions like osteoarthritis. These attributes underscore its multifaceted role in bone metabolism. This article reviews the literature, including in vitro and in vivo studies primarily on rodent models, demonstrating salidroside's efficacy in mitigating bone loss, preserving bone microarchitecture, and accelerating fracture healing. Future research directions to explore salidroside’s applications in bone-related diseases are also highlighted.

Some evidence supports the influence of the implant macro-design and primary stability. Additionally, tactile perception can be used to assess implant stability when placing the implant. This research aimed to quantify the primary and secondary stability of three implant systems with two different macro geometries (cylindrical and conical) determined through the insertion torque and the implant stability quotient (ISQ) at the moment of implant placement as a function of implant-related factors (length, width, dental arch, and implant location in the arch), intraoperative factors (bone density determined subjectively by the clinician's tactile perception), and patient-related factors (age, gender and bone density determined objectively in the cone beam computed tomography (CBCT). Methods: 102 implants of three implant systems with two different macro geometries (conical and cylindrical) were placed in 53 patients. The insertion torque, the ISQ at the implant placement (ISQ0), and bone quality according to the clinician's tactile sensation were recorded on the day of the surgery. After a three-month healing period, the ISQ was re-evaluated (ISQ3). Results: Cylindrical implants exhibited significantly higher insertion torque and ISQ at the moment of the surgery and after three months than conical implants. Cylindrical implants also showed significantly lower indices of tactile evaluation of bone quality during the implant placement surgery. However, no differences were demonstrated in the bone density measured objectively in the CBCT. (4) Conclusions: The cylindrical implants achieved the highest values for primary stability (Ncm and ISQ) and secondary stability (ISQ after three months). Insertion torque was the variable that most influenced ISQ on the day of the surgery. Implant location (incisors-canines, bicuspids-molars) and the implant macro geometry were the variables that most influenced the secondary stability (ISQ at three months).

The aim of the study was the comparison of conventional sintering versus additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects but it has its limitations. Alloplastic bone grafting using synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly and current research was focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the thereby produced β-TCP implants. The 3D-printed β-TCP hybrid structure implant was fabricated using two components, a column structure and a freeze-foam, which were sintered together. The conventionally manufactured ceramics were made by pouring. Both scaffolds were characterized according to porosity, mechanical properties and biocompatibility. The hybrid structure had a total porosity of 74.4 ± 0.5%. Microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, significantly lower than the microporous β-TCP implant’s with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all β-TCP implants, with minimal cytotoxicity. This study provides valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

Abstract: A biomaterial is proposed for closing extensive bone defects in the maxillofacial region. The composition of the biomaterial includes high-molecular chitosan, chondroitin sulfate, hyaluronate, heparin, alginate and inorganic nanostructured hydroxyapatite. The purpose of the study is to demonstrate morphological and histological early signs of reconstruction of a bone cavity of critical size. The studies were carried out on 84 white female rats weighing 200-250 g. The study group consisted of 84 subjects in total, 40 in the experimental group and 44 in the control group. In all animals, three-walled bone defects measuring 0.5 x 04 x 05 cm were applied subperiosteally in the region of the angle of the lower jaw and filled in experimental group using lyophilized gel mass of chitosan-alginate-hydroxyapatite (CH-SA-HA). In control animals, the bone cavities were filled with an auto-blood clot after bone trepanation and bleeding. The observation periods are 3.5.7 days, 2.3.4.6.8 and 10 weeks. The control of bone regeneration was carried out using multiple morphological and histological analyses. Results showed that following implantation the chitosan construct actively replaced early-stage defects with the formation of a full-fledged new bone tissue as compared to the control group. Already, by the 7th day morphological analysis showed that formation of spongy bone tissue could be seen. After 2 weeks there was a pronounced increase in bone volume (P<0.01), and at 6 weeks after surgical intervention the closure of the defect was 70-80%, after 8 weeks - 100% without violation of bone morphology with a high degree of mineralization. Thus, the use of modified chitosan after filling eliminates bone defects of a critical size in the maxillofacial region, reveals early signs of bone regeneration, and serves as a promising material in reconstructive dentistry.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

Periprosthetic fractures of the proximal femur are one of the most frequent causes of revision after total hip arthroplasty. Internal fixation may be chosen if the hip implant is stable or if a stable fixation may be obtained. Preservation of bone perfusion and adequate stability are essential for successful fracture healing. As presented in this report, a patient developed both osteonecrosis and atrophy of the cortical bone due to use of a specific plate to treat a periprosthetic fracture of the femur. An 82-year-old female sustained a periprosthetic fracture of the proximal femur two years after cemented hemiarthroplasty. The fracture was treated by plate fixation. Along the proximal femoral diaphysis, cerclages were applied to avoid interference of screws with the femoral stem. Due to postoperative restrictions and finally due to pain, the patient never could be mobilized out of a wheelchair. After 4 years, pain persisted while the fracture had healed without loosening of the joint replacement components. However, pronounced atrophy of the whole femur was present, with devitalized areas of the bone underlying the plate. When not strictly applied as an internal fixator at a distance from the bone, the plate model used in this case may disturb periosteal blood flow, causing osteonecrosis. Furthermore, high bending rigidity of the plate-bone construct may lead to stress shielding and atrophy. The case illustrates that design and mechanical properties of a plate are relevant in bone biology and healing.conclusions. Clinical trial abstracts should include items that the CONSORT group has identified as essential.

Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In this study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nanohydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrude-based printing. Rheological tests perfomed on crosslinked hydrogels confirm the formation of solid-like structures, consistently indicating a superior storage modulus in relation to the loss modulus. The swelling behaviour analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlueTM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favoured a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2), in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and therefore provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro.

Background: To prevent excessive compression of the cortical layer, which can lead to marginal bone loss, various companies have introduced specialized drills. However, these drills often lack the necessary precision, as the operator’s hand may not be stable enough to prevent ovalization and over-widening, nor precise enough to maintain coaxial alignment. Therefore, the aim of this study was to develop a device capable of achieving calibrated cortical preparation in terms of both dimension and coaxiality. Methods: A machining technology based on drilling principles was employed to create the device. Results: Nine blades were incorporated between the transmucosal neck and the implant threads, enabling the blades to cut the cortical bone coaxially during the implant insertion process. Conclusions: The implant with integrated blades was engineered to facilitate precise cortical bone preparation, ensuring both accurate dimensions and coaxial alignment. This ensures that the radial compressive stresses transmitted from the implant to the peri-implant bone during surgery can be precisely controlled. The experimental study outcomes discussed in this article validate the effectiveness of the implant design.

Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoporosis. The purpose of the study was to evaluate changes in several bone health indicators and metabolic biomarkers in postmenopausal women, with high osteopenia or osteoporosis, followed by a nutritional intervention program. 115 apparently healthy postmenopausal women (52±8 years old) were randomized into four groups: group I (n=40) received daily 1000 mg vitamin C, 100 mcg vitamin D3, 500 mg calcium(Ca) and 300 mg magnesium (Mg); group II (n=42) received daily 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; group III (n=18) received daily 5 mg bisphosphonates, 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; and group IV (n=15) received daily about 364 mg polyphenols via an innovative functional food (50 g olive paste enriched with mountain tea extract) along with 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in bone health indicators and metabolic biomarkers were assessed at the beginning and at the end of the study. Anthropometric indices and whole-body bone mineral density (BMD) were also evaluated at the beginning and at the end of the intervention period. The results revealed improved elevated levels of 25(OH)D3, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). Significant positive changes were recorded, for whole-body BMD, in all four study groups. Significant beneficial changes for total cholesterol were observed in group IV (-2.07%, P&lt;0.05) and positive changes in group I for HDL biomarker (+61.62%, P&lt;0.05). Additional larger-scale clinical trials and intervention studies are considered essential, to fully investigate and elucidate associations between dietary components and biochemical indices of bone health.

Abstract. Introduction: BMD study gives partial information on bone health in patients with TSH suppression therapy due to Differentiated Thyroid Cancer (DTC). TBS, a new parameter of bone microarchitecture is propose for bone quality study. This study analyze their long-term use in patients with DTC. Methods: BMD was measured by DXA and TBS with iNsigth software in 145 postmenopausal DTC patients. Vertebral Fractures (VFs) with a semi-quantitative x-ray method. Results: BMD at the end study was not different from initial. TBS decreased from 1.35±0.1 to 1.27±0.1 (p=0.002). PTH, Osteocalcin, and BAP were increased, suggesting increased bone remodeling. There was an increase in osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%); 31% had partially degraded and 15.1% degraded TBS changed to 48,9% and 24,8% at the end study. VFs in 30 patients, was not different in age, BMI, calcium and alcohol ingestion, smoking, radioiodine, or thyroid parameters vs. without VFs. Odds ratio for VFs increased with osteopenia (OR 2.63). Combination of TBS plus TBS did not improve discrimination. Conclusions: TBS was lowered while BMD did not differ. Percentage of osteoporosis and osteopenia and of partially degraded and degraded TBS was higher at the end study. Predominant discordance rate was found in partially degraded microarchitecture, in which the proportion of osteopenia was higher than normal or osteoporotic patients. AUC of TBS plus BMD did not improve discrimination. TBS, radioactive iodine, and sedentary lifestyle were the main differential data for patients with DTC and VFs.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin rings formation, and lowers osteoclastogenesis-related gene expression (cathepsin K, CTR, TRAF6, TRAP, MMP-9). It also impedes NFATc1, c-Fos, NF-κB, and MAPK signaling pathways, and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis, osteoblast differentiation and increases Runx2 and OCN expression. In vivo studies show its effectiveness in enhancing BMD in PMOP mice, re-straining osteoclast maturation, and increasing active osteoblast percentage in bone tissue. It modulates mRNA expressions (increasing EEF2 and decreasing HDAC1, thereby activating os-teoprotective epigenetic mechanisms) and alters various serum markers, including decrease of CTX-1, TRAcp5b, RANKL, M-CSF, TRAP, and increase of ALP and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic MMP-3, IL-6, TNF-α, and en-hances anti-osteoporotic IL-10 and TIMP3 expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

(1) Background : Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoposrosis. The purpose was to evaluate changes in biomarkers of bone metabolism, and cardiometabolic health in postmenopausal women, with high risk of osteoporosis, followed by a nutritional intervention program. (2) Method: It was a prospective randomized controlled trial. A sample of 115 apparently healthy postmenopausal women(45 -75 years of age) randomized into four groups: (I) nutritional intervention group(n=40) received daily 1000mg vitamin C, 500mg vitamin D3, 500mg calcium(Ca) and 300mg magnesium (Mg); (II) control group(n=42) received daily 500mg vitamin D3, 500mg Ca and 300mg Mg; (III) nutritional intervention group (n=18) received daily 150mg bisphosphonates, 500mg vitamin D3, 500mg Ca and 300mg Mg; and (IV) nutritional intervention group (n=15) received daily about 364 mg polyphenols via an innovative functional food (50g olive paste enriched with mountain tea extract) along with 500mg vitamin D3, 500mg Ca and 300mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in calciregulatory hormone parathormone (PTH) were evaluated at the beginning of the study as well as at 5 and 12 months intervals. Blood levels of vitamin D, vitamin C, Ca, Mg and the lipid profile were assessed at the beginning and at the end of the study. Anthropometric indices (weight, body fat(Kg), Body Mass Index(BMI) and bone mineral density(BMD) were evaluated at the beginning and at the end of the study. Statistical analysis was performed with IBM-SPSS Statistics-21. The level of statistical significance was set at p<0.05. (3) Results: 25(OH)D3 levels were improved, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). PTH levels were increased at the end of the intervention period, for groups I and IV. Significant positive changes recorded, in total BMD, in all four study groups. Significant beneficial changes for total cholesterol was observed in group IV (-2.07%, P<0.05) and positive changes in group I for HDL biomarker (+61.62%, P<0.05) (4) Conclusions:. Additional larger-scale clinical trials and intervention studies are considered essential, in order to fully investigate and elucidate associations between dietary components and biochemical indices of bone metabolism.

Pain in osteoarthritis (OA) results from erosion of joint cartilage, resulting in bone contacting bone without an intervening cushion. The periosteum, including its nociceptive innervation, ends at the border of the cartilage meaning that there is no extrinsic neuronal pathway between the opposing denuded bone surfaces to carry a bone-on-bone pain signal to the brain. The pain signaling pathway must therefore originate in nociceptive sensory endings within the subchondral bone itself. Selective ablation of this intrinsic nerve pathway, using any of a variety of approaches, is expected to permanently eliminate OA pain.

Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

Aim: the purpose of the present prospective, case series study were to report implant survival rate and marginal bone remodeling expected five years after loading using dental implants placed in in the daily practice. Material and Methods: this research was designed as an open-cohort, prospective case series study. Any completely or partially edentulous patients scheduled to receive at least one bone leve were considered eligible for this study. Primary outcomes were: cumulative implant (ISR) and prosthetic (PSR) survival rates, and any complications experienced up the five years follow-up. Secondary outcomes were: marginal bone remodeling, implant insertion torque, implant stability quotient (ISQ), and thickness of gingival biotype. Results: ninety consecutive patients (34 males and 56 females; mean age 53.2±15.4 years; range of 24–81 years), 243 implants were placed and followed for at least five years after loading (mean of 65.4±3.1 months; range of 60–72 months). The mean implant insertion torque was 42.9±4.8 Ncm (range from 15 to 45 Ncm). Overall, 83.5% of the implants (n=203) were placed with an insertion torque between 35 and 45 Ncm. At the one year follow-up, no drop-outs were recorded, but 17 patients (18.9%) with 18 restorations (12.6%) delivered on 34 implants (14%) were lost at the five years examination. At the five-year examination, six implants failed in six patients, resulting in a cumulative ISR of 97.5%. At the five-year follow-up, four prostheses failed (2.8%) resulting in a cumulative PSR of 97.2%. At the five-year examination, five complications were reported by five different patients, resulting in a prosthetic success rate of 96.5%, measured at patient level. Five years after loading, mean MBL was 0.41 ± 0.30 mm (95% CI: 0.26–0.34). Difference from the one year data was 0.04 ± 0.19 mm (95% CI: 0.01–0.07). The mean ISQ value at implant placement was 71.6 ± 5.5 (range of 45–88). Six months later, the mean ISQ was 76.7 ± 4.4 (range of 66–89). The difference was statistically significant (P=0.0001). Statistically significant higher MBL was found for smokers, and patient with thin gingival biotype. Conclusions: High implant survival and success rates could be expected with stable marginal bone remodeling up to five years after loading. Smoking and thin tissue biotype were the most important variabilities associated with higher MBL. Further research are needed to confirm these results.

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

Bone is a dynamic tissue with the capacity of repair and regeneration in specific conditions. Nevertheless, due to the increased incidence of bone disorders, the need of bone grafts has been growing over the past decades and the development of an ideal bone graft with optimal properties remains a clinical challenge. This review addresses the bone properties (morphology, composition and their repair and regeneration capacity) and puts the main focus on the potential strategies for developing bone repair and regeneration materials. It describes the requirements for designing a suitable scaffold material, types of materials (polymers, ceramics and composites) and techniques to obtain the porous structures (additive manufacturing techniques/robocasting or derived from marine skeletons) for bone tissue engineering applications. The main objective of this review is to gather the knowledge on the materials and methods for the production of scaffolds for bone tissue engineering and highlighting the potential of natural porous structures such as marine skeletons as promising alternative bone graft substitute materials without any further mineralogical changes, or after partial or total transformation into calcium phosphate. The suitability of the marine-derived porous bone graft substitutes for the intended applications will be also discussed.

Pericytes, as perivascular cells, are present in all vascularized organs and tissues, and they actively interact with endothelial cells in capillaries and microvessels. Their involvement includes functions like blood pressure regulation, tissue regeneration, and scarring. Studies have confirmed that pericytes play a crucial role in bone tissue regeneration through direct osteodifferentiation processes, paracrine actions, and vascularization. Recent pre-clinical and clinical experiments have shown that combining perivascular cells with osteogenic factors and tissue-engineered scaffolds can be therapeutically effective in restoring bone defects. This approach holds promise for addressing bone-related medical conditions. In this review, we have emphasized the characteristics of pericytes and their involvement in angiogenesis and osteogenesis. Furthermore, we have explored recent advancements in the use of pericytes in preclinical and clinical investigations, indicating their potential as a therapeutic resource in clinical applications.

Intense alterations of mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and represent an important cause of morbidity and decreased quality of life. These disor-ders have traditionally been defined as renal osteodystrophy and classified based on bone biop-sy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been difficult to adequately evaluate renal osteodystrophy in pe-diatric CKD. This has led to suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new term used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances of cal-cium, phosphate, parathyroid hormone and vitamin D, bone abnormalities and soft tissue calci-fication. This literature review aims to explore the pathogenesis, diagnostic approach, and treat-ment of CKD-MBD in children and the specific consequences of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Fractures are the most common large organ trauma in humans. The initial inflammatory re-sponse promotes bone healing during the initial post-fracture phase, but chronic and persistent inflammation due to infection or other factors does not contribute to the healing process. The precise mechanisms by which immune cells and their cytokines are regulated in bone healing remain unclear. The use of mesenchymal stem cells (MSCs) for cellular therapy of bones injury is a novel clinical treatment approach. Bone progenitor MSCs not only differentiate into bone, but also interact with the immune system to promote the healing process. We review in vitro and in vivo studies on the role of the immune system and bone marrow MSCs in bone healing and their interactions. A deeper understanding of this paradigm may provide clues to potential therapeu-tic targets in the healing process, thereby improving the reliability and safety of clinical applica-tions of MSCs to promote bone healing.

Gilbert Syndrome, is a benign condition characterized by persistent indirect hyperbilirubinemia due to reduced UDP-glucuronyltransferase enzyme activity. Its coexistence with other clinical disorders has important clinical and pharmacological implications. GS is known to coexist with many hemolytic conditions and may lead to diagnostic difficulty and also increased incidence of gallstones. UGT1A1 gene has been shown to be involved in the conjugation of various physiologically important endogenous and exogenous compounds, so individuals with Gilbert mutation (the variant allele UGT1A1*28) have an increased risk of toxicity of various drugs and endogenous compounds like irinotecan, steroid hormones, implicated in various human carcinoma like colorectal and breast carcinoma. Deferiprone (DFP) is an orally available chelator used in the management of iron overload in patients with Transfusion Dependent Thalassemia (TDT). In this study, fifteen out of 275 patients with TDT, had a deferiprone-induced joint deformity. Among these fifteen patients with joint deformity, eleven patients (four patients were homozygous for TA 7 repeats and seven were heterozygous for TA7 repeats) had associated gilbert mutation. Therefore, we hypothesize that patients of TDT who had underlying Gilbert mutation might have decreased enzymatic activity of UGTIA6, which metabolizes the DFP, leading to more prominent adverse effects related to DFP.

Aim: In a human pilot case, we used a root formed temporary prosthetical device (Intra-alveolar Device - IAD), to investigate the effect of mechanical stimulation on hard tissue clinically and radiographically. Background: The extraction of a tooth determines the resorption of the alveolar bone. This determines challenge to place an implant and to integrate the prosthesis in soft tissue. Mechanical stimulation is fundamental for bone tropism but is not understood the effect of mechanical stimulation on post-extraction site. Case presentation: A 24 years old woman was enrolled. The IAD’s were used as expected by protocol. Clinical healing was uneventfully. Vertical radiographical bone resorption measured on CBCT was -0,14mm (5,6%) while horizontal bone resorption was -0,21mm (12,36%). Conclusion: This study demonstrated the feasibility of the proposed model. We need clinical prospectical studies enrolling more patients

Large volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics including immune responses follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to 3 years we have established a well characterized large segmental tibial bone defect ovine model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups in which all ovine segmental defects were treated with a bone grafting technique combined with a three-dimensionally printed medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold. The qualitative data set is based on osteoimmunological findings gained from IHC analyses of over &gt;350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research.

To evaluate the relative importance of IGF-I expression in various cell types for endochon-dral ossification, we quantified the trabecular bone at the secondary spongiosa and epiphysis of the distal femur in 8-12-week-old male mice with a global knockout of the Igf-I gene as well as conditional deletion of the Igf-I gene in osteoblasts, chondrocytes, osteo-blasts/chondrocytes, and their corresponding control wild type littermates. The osteoblast-, chondrocyte- and osteoblast/chondrocyte-specific Igf-I conditional knockout mice were generated by crossing Igf-I floxed mice with Cre transgenic mice in which Cre expression is under the control of Col1α2 or Col2α1 promoter. We found that global disruption of Igf-I resulted in 80% and 70% reduction in bone size, which is defined as total volume, at the secondary spongiosa and epiphysis of the distal femur, respectively. Abrogation of Igf-I in Col1α2-producing osteoblasts, but not Col2α1-producing chondrocytes, decreased bone size by 25% at both the secondary spongiosa and epiphysis while deletion of the Igf-I globally or specifically in osteoblasts or chondrocytes reduced trabecular bone mass by 25%. By contrast, global Igf-I knockout but not conditional knockout of Igf-I in osteoblasts and/or chondrocytes reduced trabecular bone mass in the epiphysis. The reduced trabecu-lar bone mass at the secondary spongiosa in osteoblast- and/or chondrocyte-specific Igf-I conditional knockout mice is caused by reduced trabecular number and increased trabec-ular separation. Immunohistochemistry studies revealed that expression levels of chon-drocyte (COL10, MMP13) and osteoblast (BSP) markers were reduced in the secondary spongiosa and the epiphyses in the global Igf-I knockout mice. Our data indicate that local and endocrine IGF-I actions in bone are pleiotropic and dependent on cell type as well as the bone compartment where IGF-I acts.

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

Chronic Myeloid Leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a Tyrosine Kinase Inhibitor (TKI), can be effectively used as therapy for CML. However, imatinib can affect bone turnover, thus having clinical implications on the bones of CML patients undergoing long-term imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving imatinib still need further study. A combination of imaging techniques such as Bone Mineral Density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and Osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving imatinib. This article explains the rationale for using BMD, CTX-1, and Osteocalcin as monitoring parameters of bone remodeling in CML patients receiving imatinib. First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of imatinib on BMD, CTX-1, and Osteocalcin will be explained. In conclusion, the assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and Osteocalcin.

Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In the current study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nano-hydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrusion-based printing. Rheological tests perfomed on crosslinked hydrogels confirm the formation of solid-like structures consistently indicating a higher storage modulus compared to the loss modulus. The swelling behaviour analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlueTM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favoured a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2), in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro.

Vertical and horizontal bone augmentation is one of the most challenging techniques in bone engineering. The use of barrier membranes and scaffolds in guided bone regeneration (GBR) procedures is a common approach for the treatment of lost bone around teeth and dental implants. The aim of this study was to estimate the barrier effects of a synthetic poly (lactic acid/caprolactone) [P(PA/CL)] bilayer membrane for GBR, compared to a porcine collagen bilayer membrane, in the vertical augmentation model on 10–12-months old rat skull without periosteum. The HAp block (diameter: 4 mm, height: 3 mm, porosity:75%, average pore size:150 μm) was placed on the rat skull without a periosteum. The P(LA/CL) membrane (solid layer: 25 μm, porous layer: 175 μm) or the collagen membrane (solid layer, porous layer) was applied onto the HAp block. At 3, 6, and 12 weeks after the surgery, the incised tissues were fixed, decalcified, and stained with hematoxylin and eosin for histological evaluation. The P(LA/CL) membrane remained until 12 weeks and could achieve barrier effects to inhibit cellular invasion from the repositioned soft tissues. Local bone formation occurred in the interconnected pores of HAp at 6 weeks. On the other hand, the collagen membrane did not inhibit cellular invasion for its expansion until 3 weeks, and was absorbed until 6 weeks. The results indicated that the P(LA/CL) membrane might be effective in GBR as occlusive absorbable membrane.

Background: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous β-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a β-TCP ceramic and higher biodegradability than pure alginate. Methods: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. Results: Daptomycin and the model compound FITC protein A (n=30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9 % were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing, the current stem cell interventions that disrupt or augment the bone healing process, and finally, consider the future direction/therapeutic options related to stem cells and bone healing.

Bone is the second most frequent site of metastases from differentiated thyroid carcinoma (DTC). Bone metastases (BM) occurs in about 10% of all patients with DTC. They are more frequently observed in follicular thyroid carcinoma (FTC) (7-28%), than in thyroid papillary carcinoma (PTC) (1-7%) [1,2] and are associated to unfavorable clinical out-comes, mainly related to skeletal related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions and hypercalcemia, which impair the quality of life and reduce life expectancy. BM from DTC require multimodal and comprehensive treatment, including radioiodine therapy (RAI), palliative treatment, surgical treatment, external beam radiation and target drug therapy. RAI is the first line treatment, but about two thirds of DTC patients with distant metastases are not definitively cured. This treatment is considered less effective in BM particularly in case of large metastases. The different response to RAI treatment alone or associated to BM focal treatment depends to RAI avidity of lesions [3]. We report the rare case of an excellent response to RAI of a metachronous bone metastasis of skull from FTC, in a 72 yrs old woman, diagnosed 15 years after the first treatment, followed by a complete regression of radioiodine up-taking area with persistence of excellent response to the treatment six years after it. This case confirms that the complete BM response to RAI treatment depends to the degree of dedifferentiation of cancers cells and enforce the concept of a long- life follow-up of FTC patients.

Introduction: Silver nanoparticles have been extensively investigated in dental and orthopedic materials. However, the impregnation of bone graft with silver nanoparticles has been poorly investigated. Objectives: The aim of this study was to evaluate the in vitro antibiofilm activity of a bovine bone impregnated with silver nanoparticles. Methods: Bone scaffolds from cancellous bovine femur were used for the tests and impregnated with silver nanoparticles (50nm) by physical adsorption. Silver nitrate minimal inhibitory and bactericidal concentration were performed Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Enterococcus faecalis, Acinetobacter baumannii, and Escherichia coli. Disc diffusion tests for silver nanoparticles susceptibility and quantification of biofilm production on plate and bone with sessile cell count were also performed. Results: All pathogens were susceptible to silver with low minimal inhibitory concentration (0.25 – 4 mg/L). The scaffold impregnated with silver nanoparticles presented a significant reduction in the biofilm cells for all microorganisms with a reduction of more than 3 logs in colony forming units count. Conclusion: Bone scaffolds impregnated with silver nanoparticles can significantly reduce biofilm, and it can be a strategical material to be used as an implant for different approaches.

Background: Electrical conductivity of trabecular bone at 100 kHz was recently reported as a good predictor of bone volume fraction. However, to quantify its relationship with the free water (or physiological solution) content and between the conductivities of its constituents, is still unclear. Methods: In this contribution, in silico models inspired by microCT images of trabecular bovine samples were used to build realistic geometries. Finite Element Method was applied to solve the electrical problem and to robustly fit the conductivity of the constituents with literature data. The obtained effective electrical conductivity was compared to Bruggeman three media mixture model: physiological solution, bone marrow and bone matrix. Results: The values for physiological solution plus bone marrow and bone matrix that captured better the bone volume fraction in the two media Finite Element model were: σps+bm = 298.4 mS/m and σb = 21.0 mS/m, respectively. Additionally, relative good results were obtained by a three media Bruggeman mixture model with σbm= 103 mS/m, σb= 21.0 mS/m, and σps= 1200 mS/m. Simple linear relationships between the proportions of constituents depending on bone volume fraction were tested. Degree of anisotropy and fractal dimension do not show detectable changes in effective conductivity. Conclusions: These results provided some useful findings for simulation purposes: first, a higher value of electrical conductivity of bone marrow has to be used in order to obtain similar values to those experimental published data. Second, anisotropy is not detectable by conductivity measurements for small trabecular samples (cube 5 mm). Finally, the simulations presented here showed a relatively good fitting of the mixture Bruggeman model which potentially would allow both, accounting for the free water content and re-scaling the model for whole bone electrical simulations.

Osteitis fibrosa cystica (OFC) and Brown Tumour are two related but distinct types of bone lesions that result from overactivity of osteoclasts most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions placing them in the spectrum of RAS-MAPK-driven neoplasms, while until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumour such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumour includes clinical symptoms involving chronic bone pain and laboratory finding of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically both lesions are characterized by clustered osteoclast in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumour.

A potential association between hematopoietic stem cell status in the bone marrow and the surrounding bone tissue has been hypothesized, and some studies have investigated the link between blood count and bone mineral density (BMD), although their exact relationship remains controversial. Moreover, biological factors linking the two are largely unknown. In our present study, we found no clear association between platelet count and BMD in the female group, with aging having a very strong effect on BMD. On the other hand, a significant negative correlation was found between platelet count and BMD in the male group. As a potential mechanism, we examined whether megakaryocytes, the source of platelet production, secrete cytokines that regulate BMD, namely OPG, M-CSF, and RANKL. We detected the production of these cytokines by megakaryocytes deriving from bone marrow mononuclear cells and found that RANKL was negatively correlated with BMD. This finding suggests that RANKL production by megakaryocytes may mediate the negative correlation between platelet count and BMD. To our knowledge, this is the first report to analyze bone marrow cells as a mechanism for the association between blood count and BMD. Our study may provide new insights into the development and potential treatment of osteoporosis.

We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). 8 PanNENs patients developed BMets, and 107 remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BM-PanNENs patients vs. non-BM-PanNENs patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated BM-PanNENs from non-BM-PanNENs patients; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. Based on CBMs metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125 and CY18 combination 93/90%, respectively. The useful CBMs for BM-PanNENs patients detection were CA125, CY18, and B2M. They seem to have the diagnostic capacity as a fair single biomarker and CA125&CY18 combination panel for the detection of BMets.

ABSTRACT: Understanding the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, including the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA pathophysiology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms has been characterized as underlying causes of pain chronicity. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. This review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insight on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

The number of patients with bone metabolic disorders including osteoporosis is increasing worldwide. These disorders often facilitate bone fractures, which seriously impact the patient’s quality of life and could lead to further health complications. Bone homeostasis is tightly regulated to balance bone resorption and formation. However, many anti-osteoporotic agents are broadly categorized as either bone forming or anti-resorptive, and their therapeutic use is often limited due to unwanted side effects. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aims to clarify the bone protecting effects of oat bran water extract (OBWE) and its mode of action. OBWE inhibited RANKL-induced osteoclast differentiation by blocking c-Fos/NFATc1 through the alteration of I-κB. Furthermore, we found that OBWE enhanced BMP-2-stimulated osteoblast differentiation by the induction of Runx2 via Smad signaling molecules. In addition, the anti-osteoporotic activity of OBWE was also evaluated using an in vivo model. OBWE significantly restored ovariectomy-induced bone loss. These in vitro and in vivo results showed that OBWE has the potential to combat bone metabolic disorders including osteoporosis

Objective: Regeneration of bone defects remains a challenge for maxillofacial and reparative surgeons. The purpose of this histological study was to assess the osteogenic potential of octacalcium phosphate (OCP) and bone matrix gelatin (BMG) alone and in combination in artificially created mandibular bone defects in rats. The quality of the newly formed bone was also evaluated. Methods: Thirty-six male Sprague Dawley rats (6-8 weeks old with 120-150 g weight) were randomly divided into four groups. Defects (3 mm in diameter and 2 mm in depth) were created in the mandible of rats and filled with 6 mg of OCP, BMG or a combination of both (1/4 ratio), respectively. Defects were left unfilled in the control group. To assess osteoinduction and bone regeneration and determine the quality of the newly formed bone, tissue specimens were harvested at seven, 14, and 21 days post-implantation. The specimens were processed, stained with hematoxylin and eosin (H&E) and histologically analyzed under light microscopy. Results: In the experimental groups, new bone formation was initiated at the margins of defects from seventh day after implantation. At the end of the study period, the amount of the newly formed bone increased and the bone was relatively mature. Osteoinduction and new bone formation were greater in OCP/BMG group. In the control group, slight amount of new bone had been formed at the defect margins (next to host bone) on day 21. Conclusion: Combination of OCP/BMG may serve as an optimal biomaterial for treatment of mandibular bone defects.

Currently, drug screening is primarily based on human cell culture for initial high-throughput screening, and subsequently, rodent model to confirm the biological effects. However, the mammalian system is known for time-consuming and highly-cost to be difficult to perform high-throughput drug screening, which exists a critical gap between in vitro cell-based models and the in vivo mammalian models. Therefore, the zebrafish could bridge this gap in preclinical toxicity screening along the drug development pipeline because of its efficiency. We aimed to develop an in vivo zebrafish platform for rapid drug screening. Zebrafish, due to its high genomic conservation with mammals and rapid development and differentiation, it has many advantages, such as short life span, large number of offspring and low cost, easy manipulation for generating transgenic species, to serve as animal model for disease-based research. In 96-well microplates, zebrafish embryos were incubated with small molecular compounds that affected bone mineralization. The level of osteogenic mineralization was evaluated by fluorescent dye staining and quantified by image analysis software. Quantitative real time-PCR (qRT-PCR) was performed to evaluate the biological pathways involved in bone metabolism at the molecular level. The system was validated by demonstrating that response to alendronate and Dorsomorphin in zebrafish. In our study, we screened for 24 compounds within the CYCU-1120~1152 chemical library and identified 3 compounds, pentamidine (CYCU-1140), BML-267 (CYCU-1147), and alendronate (CYCU-1152), increased embryonic mineralization; while 6 compounds, RWJ-60475 (CYCU-1126), levamisole HCL (CYCU-1128), tetramisole HCL (CYCU-1129), fenvalerate (CYCU-1132), NSC-663284 (CYCU-1138), and BML-267ester (CYCU-1148), were inhibitory to bone mineralization. We also found that alendronate enhanced the level of bone mineralization by inhibiting osteoclast-related genes. To sum up, our research showed that zebrafish may have potential to be a drug-screening and mechanism-analysis platform for bone mineralization.

The study aimed to evaluate implant success and bone height variations after transcrestal sinus floor elevation (tSFE) using the osseodensification technique (OD) combined with beta-tricalcium phosphate (β-TCP), as bone graft material and simultaneous implant placement. Thirteen patients requiring the placement of one implant in the upper posterior maxilla, with a residual bone height of

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

Titanium micro-scale topography results in excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1–5 µm) and sub-micro-scale (0.1–0.5 µm) topographies and machined titanium. Average roughness was 12.5 ± 0.65 nm, 123 ± 6.15 nm, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. The micro-rough surface showed the fewest cells attaching during the initial stage and the lowest proliferation. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface and lowest on the machined surface. Bone-to-implant integration was strongest for the micro-rough surface, consistent with it having the greatest ability to retain cells in vitro. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation and enhances the rate of osteoblastic differentiation over that of micro-rough titanium; however, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking compared to that of micro-rough titanium.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Objective: To evaluate the clinical efficacy of antibiotic bone cement plus lateral bone repositioning for severe diabetic foot and its impact on wound healing rate. Methods: Sixty patients with hemodialysis anemia admitted to the endocrinology department of our hospital from July 2020 to July 2021 were included and randomly assigned to receive antibiotic bone cement plus lateral bone repositioning (observation group) or vacuum sealing drainage (VSD) (control group). Outcome measures included skin temperature of the affected limb, ankle-brachial index, sensory threshold, foot wound healing, dorsalis pedis artery hemodynamics, lower limb function and clinical efficacy. Results: Antibiotic bone cement plus lateral bone repositioning resulted in significantly higher treatment efficiency and transcutaneous partial pressure of oxygen, smaller wound, and lower trauma pH versus VSD, suggesting that antibiotic bone cement plus lateral bone repositioning contributes to potentiating the treatment efficacy and reducing the foot ulcer trauma, thereby facilitating rapid recovery. Patients given antibiotic bone cement plus lateral bone repositioning had larger vascular internal diameter and blood flow and better sensory conduction velocity of the common peroneal nerve and the motor conduction velocity of the tibial nerve versus those given VSD, indicating its vascular and neurological benefits. Conclusion: Antibiotic bone cement plus lateral bone repositioning enhances the treatment efficiency, boosts trauma healing, and promotes postoperative functional recovery of patients.

Cost-effective and functionalized scaffolds are in high demand for stem-cell-based regenerative medicine to treat refractory bone defects in craniofacial abnormalities and injuries. One potential strategy is to utilize pharmacological and cost-effective plant polyphenols and biocompatible proteins, such as gelatin. Nevertheless, the use of chemically modified proteins with plant polyphenols in this strategy has not been standardized. Here, we demonstrated that gelatin chemically modified with epigallocatechin gallate (EGCG), the major catechin isolated from green tea, can be a useful material for dedifferentiated fat cells and adipose-derived stem cells and can induce bone regeneration in a rat congenial cleft-jaw model in vivo. Vacuum-heated gelatin sponge modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponge (vhGS). The EGCG-modification converted the water wettability of vhGS to a hydrophilic property (contact angle: 110° to 3.8°) and the zeta potential to a negative surface charge; the modification enhanced the cell adhesion property and promoted calcium phosphate precipitation. These results suggest that the EGCG-modification with chemical synthesis can be a useful platform to modify the physicochemical property of gelatin. This alteration is likely to provide a preferable microenvironment for multipotent progenitor cells, inducing superior bone formation in vivo.

Biomaterials have assumed a decisive role in modern medicine by enabling significant advancements in medical care practices. These materials are designed to interact with biological systems, offering substantial solutions for various medical needs. In this research, bioceramic materials consisting of a bioactive hydroxyapatite-based matrix with Ti nanoparticles, were processed as promising materials. These bioceramics were obtained using mechanical milling, uniaxial pressing, and sintering as powder processing techniques. This study evaluates the effect of Ti additions on the structural, electrochemical, and mechanical properties of the hydroxyapatite ceramic material. Titanium additions were about 1, 2 and 3 wt%. The experimental results demonstrate that the biocomposite's structure has two hexagonal phases: one corresponding to the hydroxyapatite matrix and the other to the Ti as a reinforced phase. The biomaterials' microstructure is completely fine and homogeneous. The biomaterial reinforced with 1wt. % Ti exhibits the best mechanical behavior. In this context, Electrochemical tests reveal that bio-ceramics can achieve stability through an ion adsorption mechanism when exposed to a physiological electrolyte. Bioceramics, particularly those containing 1%Ti, develop their bioactivity through the formation a high-density hydroxide film during a porous sealing process at potentials around −782.71 mV, with an ionic charge transfer of 0.43x10^-9 A/cm². Finally, this biofilm behaves as a capacitor Cc = 0.18 nF/cm², resulting in lower ionic charge transfer resistance (Rct = 1.526x106 Ω-cm²) at the interface. This mechanism promotes the material’s biocompatibility for bone integration as an implant material.

(1) Background : When placing implants in the maxillary posterior region with insufficient alveolar bone, a maxillary sinus elevation is necessary. Autogenous bone, though biologically ideal, poses risks and discomfort due to donor site harvesting. Block-type autogenous tooth bone graft material, made from the patient’s own extracted tooth, offers similar biological stability without these drawbacks; (2) Methods : This study observed the progress of 19 implant patients who were treated with maxillary sinus elevation procedures using block-type autogenous tooth bone graft material at the Daegu Catholic University Medical Center. Extracted teeth were processed into demineralized tooth block bone. After elevating the sinus membrane, implants and the tooth bone graft material were placed in the space, and the bony window was repositioned. Postoperative evaluations through clinical observation and radiographic imaging assessed sinus membrane elevation, alveolar bone height increase, and implant osseointegration; (3) Results : Results showed proportional increases in alveolar bone height to the graft material size, with long-term stability. No postoperative complications occurred, even with sinus membrane perforation, and implants remained stable; (4) Conclusions : The study concludes that maxillary sinus lifts using block-type autogenous tooth bone graft material provide excellent bone induction and biocompatibility, making it a highly beneficial method for both dentists and patients.

Background and Objectives: This study aimed to evaluate the histological and biochemical ef-fects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 grams were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n= 8), implant + capsai-cin-1 (n= 8), and implant + capsaicin-2 (n= 8). 2.5 mm diameter and 4 mm length titanium im-plants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the con-trol group. Three rats in totally were died during and after the experiment, as a result of the an-alyzes performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p> 0.05), alt-hough the bone implant connection was higher in the groups treated with capsaicin. Conclusi-ons: A positive effect on osteointegration was not observed in this study. This may be due to os-teaclast activation. However it was found that it has a positive effect on oxidative stress. Osteo-clast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p

Limb-salvage surgery is the first choice for treatment of primary or metastatic bone tumors when possible to perform. Rehabilitation plays a major role after surgery, with the aim of improving function and maintaining the highest possible quality of life. Megaprostheses are currently the most frequent type of limb reconstruction used to treat the bone defect after tumor resection and The Modular Universal Tumor And Revision System (MUTARS®)is currently among the most used tumor and revision systems. Several studies have evaluated the causes and rate of failure of this system, but only few studies investigated the rehabilitative outcomes in terms of function and quality of daily life. The aim of this narrative review is to explore the correlations between functional outcomes and quality of life after implant of MUTARS® prostheses surgery in patients with bone tumor of the lower extremities. A comprehensive search was conducted on PubMed and Scopus using the following MESH terms: “MUTARS”, “Megaprosthesis”, “bone”, “tumors”, “metastasis”, “lower limb”, “rehabilitation”, “outcome”, “quality of life”, and 12 studies were included. The most frequent oncological pathology was found to be primitive bone tumors treated with modular prosthesis. Outcome measures used were Henderson et al classification, HHS, MSTS, VAS, ROM,LSR, KPS and quality of life questionnaire. Reconstruction of the lower limbs with the MUTARS® system seemed to be a valid treatment option after bone tumor resection. Rehabilitation after MUTARS® surgery is very relevant, but currently, functional and rehabilitative outcomes are inadequately represented in the literature. Therefore, further studies are needed to define best rehabilitation protocols in clinical practice after oncological orthopedic surgery.

This review summarises the complex relationship between medications used to treat type 2 diabetes, and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density, thus we analysed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, as well as GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control and potential medication-related effects on bone.

3D Printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness, and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, by employing surface modification, combining with other materials, and incorporation of 3DP workflow can lead to better patient healing outcomes.

The phytonutraceutical Ormona® is a product composed of: purified oil of Bixa orellana Linné; dry extract of Myrciaria dubia McVaugh; dry extract of Trifolium pratense L. and dry extract of Euterpe oleracea Mart. obtained using Evolve® technology. This study evaluated the effects of Ormona® on Wistar rats affected by ovariectomy-induced osteoporosis. Pre-treatment was conducted for 15 days before surgery and continued for a further 45 days after the surgical procedure. The experimental design consisted of 5 groups (n=5): OVW: treated with distilled water (1 mL/ kg, p.o); ADS: alendronate sodium (4 mg/ kg p.o); EST: conjugated estrogen (2 ug/ kg, p.o); ORM: Ormona® (20 mg/kg, p.o); ORM + EST: Ormona® (20 mg/kg + conjugated estrogen 2 ug/ kg, p.o. Biochemical and hormonal parameters, along with bone histopathology and trabecular and femoral diaphysis size, were evaluated through Scanning Electron Microscopy (SEM) and bone calcium quantification by atomic absorption spectrophotometry. The results show that ovariectomy caused bone alterations such as loss of femoral microarchitecture, decreased bone homeostasis parameters, and changes in the lipid profile. Estrogen supplementation reduced parameters such as cholesterol, LDL, and Ca2+ concentration. However, Ormona® showed higher serum estradiol levels (p&lt; 0.01), effects on the lipid profile, including parameters that estrogen replacement and alendronate sodium did not affect, with an increase in HDL, and positive modulation of bone metabolism, increasing osteocytes and the presence of osteoblasts. Ormona®, therefore, produced better results than the groups treated with estrogen and alendronate sodium.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.