Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Burns*/therapy ; Burns*/drug therapy ; Burns*/metabolism ; Burns*/pathology ; Hydrogels*/chemistry ; Wound Healing*/drug effects; Animals ; Mice ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/cytology ; Amino Acids/chemistry ; Microvessels/metabolism ; Male ; Adipose Tissue/metabolism ; Humans ; Neovascularization, Physiologic/drug effects

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an arginine-and-chitosan-based protein-mimic hybrid hydrogel. 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 incorporated PreM1 and MVFs into ACgel1 via optimal design and fabrication. This construct delivered PreM1 to 3°-burn wounds at least up to 7 days-post-burn (dpb), and scaffolded and delivered MVFs. PreM1-MVFs-ACgel1 promoted the healing of 3°-burns in mice, including vascularization and collagen formation. The re-epithelization and closure of 3° 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 with 97% closure and 4.69% relative epithelial gap at 13 dpb compared to saline control. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of 3°-burns although PreM1-MVFs-ACgel1 is significantly more effective. These PreM1- and/or MVF-functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapeutic candidates for treating deep burns.

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R01 GM136874 United States GM NIGMS NIH HHS; 1R01GM136874 and 1R21AG066119 United States NH NIH HHS

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

0 (Hydrogels)
0 (Amino Acids)

Date Created: 20241016 Date Completed: 20241016 Latest Revision: 20241204

20241204

PMC11476471

10.3390/ijms251910378

39408708