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

被引:0
作者
Lu, Yan [1 ]
Su, Shanchun [1 ]
Chu, Chih-Chang [2 ,3 ]
Kobayashi, Yuichi [4 ,5 ]
Masoud, Abdul-Razak [1 ]
Peng, Hongying [6 ]
Lien, Nathan [1 ]
He, Mingyu [2 ,3 ]
Vuong, Christopher [1 ]
Tran, Ryan [1 ]
Hong, Song [1 ,7 ]
机构
[1] Louisiana State Univ Hlth, Neurosci Ctr Excellence, Sch Med, 2020 Gravier St, New Orleans, LA 70112 USA
[2] Cornell Univ, Dept Fiber Sci & Apparel Design, Ithaca, NY 14853 USA
[3] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA
[4] Tokyo Inst Technol, Dept Bioengn, Box B-52,Nagatsuta Cho 4259,Midori Ku, Yokohama 2268501, Japan
[5] Meiji Univ, Org Strateg Coordinat Res & Intellectual Propertie, 1-1-1 Higashimita,Tama-Ku, Kawasaki 2148571, Japan
[6] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45221 USA
[7] Louisiana State Univ Hlth, Dept Ophthalmol, New Orleans, LA 70112 USA
关键词
PreM1: pro-regenerative lipid mediator 1; 14S; 21R-dihydroxy-docosa-4Z; 7Z; 10Z; 12E; 16Z; 19Z-hexaenoic acid; or; 21R-diHDHA; 3 degrees 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; MESENCHYMAL STEM-CELLS; RESOLUTION; VASCULARIZATION; INFLAMMATION; ENHANCEMENT; STRATEGIES; DRESSINGS; INCREASES; SURVIVAL; CHITOSAN;
D O I
10.3390/ijms251910378
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 degrees) 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 degrees-burn wounds at least up to 7 days-post-burn (dpb), and scaffolded and delivered MVFs. PreM1-MVFs-ACgel1 promoted the healing of 3 degrees-burns in mice, including vascularization and collagen formation. The re-epithelization and closure of 3 degrees 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 degrees-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.<br />
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页数:19
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