Preprint Article Version 1 This version is not peer-reviewed

Amino Acid-based Protein-mimic Hydrogel Incorporating Pro-regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds

Version 1 : Received: 16 September 2024 / Approved: 16 September 2024 / Online: 16 September 2024 (13:23:31 CEST)

How to cite: Lu, Y.; Su, S.; Chu, C.-C.; Kobayashi, Y.; Masoud, A.-R.; Peng, H.; Lien, N.; He, M.; Vuong, C.; Tran, R.; Hong, S. Amino Acid-based Protein-mimic Hydrogel Incorporating Pro-regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds. Preprints 2024, 2024091242. https://doi.org/10.20944/preprints202409.1242.v1 Lu, Y.; Su, S.; Chu, C.-C.; Kobayashi, Y.; Masoud, A.-R.; Peng, H.; Lien, N.; He, M.; Vuong, C.; Tran, R.; Hong, S. Amino Acid-based Protein-mimic Hydrogel Incorporating Pro-regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds. Preprints 2024, 2024091242. https://doi.org/10.20944/preprints202409.1242.v1

Abstract

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator capable of promoting wound healing and regenerative functions of mesenchymal stem cells (MSCs), en-dothelial cells, and macrophages. The third-degree (3o) burn healing and regenerative functions of MSCs are also enhanced by ACgel1, an arginine and chitosan-based protein-mimic hybrid hy-drogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporates PreM1 and MVFs into ACgel1 via optimal design and fabrication is capable of delivering PreM1 to 3o burn wounds at least up to 7 days post-burn (dpb), and of scaffolding and delivering MVFs, which promoted 3o burn the healing in mice, including vascularization and collagen formation. The re-epithelization and closure of 3o burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s) while PreM1-MVFs-ACgel1 was most effective. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of the 3o burns. These PreM1- and/or MVFs- functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapies for overcoming the drawbacks of current skin grafting or substituting for treating severe deep burns.

Keywords

PreM1: Pro-regenerative lipid mediator 1, 14S,21R-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z, 19Z-hexaenoic acid, or 14S,21R-diHDHA; 3o-burn: third-degree burn; AA-PEA: amino acid-based poly(ester amide) polymer; UArg-PEA: unsaturated arginine-based poly(ester amide); ACgel1, UArg-PEA/Chitosan covalently coupled hydrogel 1; MVFs: microvascular fragments; PreM1-MVFs-ACgel1: PreM1-incorporated and MVFs-seeded ACgel1; blood vessel regeneration or vascularization; wound healing; collagen

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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