Purpose: This pilot ex-vivo study and first clinical experience in Italy evaluate the impact of using pre-implantation crosslinking on all-femtosecond laser-cut corneal allogenic intracorneal ring segments (AFXL CAIRS). Methods: Six human donor eye-bank corneas were used for the preclinical ex-vivo human study. Three corneas were used for AFXL CAIRS. First, they were prepared (D) with the IntraLase™ femtosecond laser (Johnson & Johnson, USA). The allogenic tissue rings were crosslinked before implantation with Riboflavin -UV-A accelerated crosslinking protocol (ACXL) with a 0.1% HPMC Riboflavin isotonic solution (Vibex Rapid, Glaukos-Avedro, USA) and the new KXL UV-A emitter (Glaukos-Avedro, USA). Three corneas were used as recipients (R) of the AFXL CAIRS. After completing the ex-vivo phase, the first two Italian patients were treated. A single ACXL CAIRS was implanted in a 51-year-old male with 53.53 D K steep, 363 m minimum corneal thickness (MCT) and a double ACXL CAIRS was implanted in a 46-year-old male patient with 58.30 D K steep and 443 m MCT. The follow-up was at three months. Results: Crosslinking of the segments enhanced tissue strength and grip, facilitating manipulation and CAIRS insertion into the recipient tunnels and the yellowish color of the crosslinked segments improved visibility. The segment’s thickness and volume remained unaltered during the follow-up. Both patients improved UDVA and BSCVA. K steep and HOAs were reduced and MCT increased. Conclusions Pre-implantation ACXL facilitated CAIRS insertion by increasing the viscoelastic consistency without altering physical characteristics and volume during the follow-up, rendering this important step a promising candidate in method standardization. Functional data and MCT improved significantly without adverse events.

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. Aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. The therapeutical peptide and proteins are remarkable therapeutic agents in today’s world that allows the treatment of severe, chronic and life‐threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis in an easy manner. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. The primary objective of this article is to review current issues concerned with the therapeutics peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. The article will also review literature concerning classification of hydrogels on different basis, polymers used, release mechanisms their physical and chemical characteristics and diverse applications.