TY - JOUR
T1 - Accelerate Healing of Severe Burn Wounds by Mouse Bone Marrow Mesenchymal Stem Cell-Seeded Biodegradable Hydrogel Scaffold Synthesized from Arginine-Based Poly(ester amide) and Chitosan
AU - Alapure, Bhagwat V.
AU - Lu, Yan
AU - He, Mingyu
AU - Chu, Chih Chang
AU - Peng, Hongying
AU - Muhale, Filipe
AU - Brewerton, Yue Liang
AU - Bunnell, Bruce
AU - Hong, Song
N1 - Funding Information:
Many thanks to Ms. Lindsey A. McGehee for editing. This work is supported by grants from the National Institutes of Health (R01-DK087800 to S. Hong and C. C. Chu) and the Research to Prevent Blindness, New York, NY. The authors thank the Becky Q. Morgan Foundation for the research funds to C. C. Chu. This work made use of the Cornell Center for Materials Research Facilities supported by the National Science Foundation under award no. DMR-1120296.
Publisher Copyright:
© 2018, Mary Ann Liebert, Inc.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Severe burns are some of the most challenging problems in clinics and still lack ideal modalities. Mesenchymal stem cells (MSCs) incorporated with biomaterial coverage of burn wounds may offer a viable solution. In this report, we seeded MSCs to a biodegradable hybrid hydrogel, namely ACgel, that was synthesized from unsaturated arginine-based poly(ester amide) (UArg-PEA) and chitosan derivative. MSC adhered to ACgels. ACgels maintained a high viability of MSCs in culture for 6 days. MSC seeded to ACgels presented well in third-degree burn wounds of mice at 8 days postburn (dpb) after the necrotic full-thickness skin of burn wounds was debrided and filled and covered by MSC-carrying ACgels. MSC-seeded ACgels promoted the closure, reepithelialization, granulation tissue formation, and vascularization of the burn wounds. ACgels alone can also promote vascularization but less effectively compared with MSC-seeded ACgels. The actions of MSC-seeded ACgels or ACgels alone involve the induction of reparative, anti-inflammatory interleukin-10, and M2-like macrophages, as well as the reduction of inflammatory cytokine TNFα and M1-like macrophages at the late inflammatory phase of burn wound healing, which provided the mechanistic insights associated with inflammation and macrophages in burn wounds. For the studied regimens of these treatments, no toxicity was identified to MSCs or mice. Our results indicate that MSC-seeded ACgels have potential use as a novel adjuvant therapy for severe burns to complement commonly used skin grafting and, thus, minimize the downsides of grafting.
AB - Severe burns are some of the most challenging problems in clinics and still lack ideal modalities. Mesenchymal stem cells (MSCs) incorporated with biomaterial coverage of burn wounds may offer a viable solution. In this report, we seeded MSCs to a biodegradable hybrid hydrogel, namely ACgel, that was synthesized from unsaturated arginine-based poly(ester amide) (UArg-PEA) and chitosan derivative. MSC adhered to ACgels. ACgels maintained a high viability of MSCs in culture for 6 days. MSC seeded to ACgels presented well in third-degree burn wounds of mice at 8 days postburn (dpb) after the necrotic full-thickness skin of burn wounds was debrided and filled and covered by MSC-carrying ACgels. MSC-seeded ACgels promoted the closure, reepithelialization, granulation tissue formation, and vascularization of the burn wounds. ACgels alone can also promote vascularization but less effectively compared with MSC-seeded ACgels. The actions of MSC-seeded ACgels or ACgels alone involve the induction of reparative, anti-inflammatory interleukin-10, and M2-like macrophages, as well as the reduction of inflammatory cytokine TNFα and M1-like macrophages at the late inflammatory phase of burn wound healing, which provided the mechanistic insights associated with inflammation and macrophages in burn wounds. For the studied regimens of these treatments, no toxicity was identified to MSCs or mice. Our results indicate that MSC-seeded ACgels have potential use as a novel adjuvant therapy for severe burns to complement commonly used skin grafting and, thus, minimize the downsides of grafting.
KW - M1-or M2-like macrophages
KW - MSC-seeded ACgels
KW - chronic inflammation
KW - hydrogels synthesized from unsaturated arginine-based Poly(ester amide) and chitosan
KW - mesenchymal stem cells
KW - severe burn
UR - http://www.scopus.com/inward/record.url?scp=85058010640&partnerID=8YFLogxK
U2 - 10.1089/scd.2018.0106
DO - 10.1089/scd.2018.0106
M3 - Article
C2 - 30215325
AN - SCOPUS:85058010640
SN - 1547-3287
VL - 27
SP - 1605
EP - 1620
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 23
ER -