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Acceleration of Diabetic Wound Regeneration using an In Situ–Formed Stem‐Cell‐Based Skin Substitute
Author(s) -
Dong Yixiao,
Rodrigues Melanie,
Kwon Sun Hyung,
Li Xiaolin,
A Sigen,
Brett Elizabeth Anne,
Elvassore Nicola,
Wang Wenxin,
Gurtner Geoffrey C.
Publication year - 2018
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201800432
Subject(s) - stem cell , wound healing , angiogenesis , neovascularization , regeneration (biology) , self healing hydrogels , medicine , chronic wound , adipose tissue , inflammation , in vivo , surgery , microbiology and biotechnology , cancer research , materials science , immunology , biology , polymer chemistry
Chronic diabetic ulcers are a common complication in patients with diabetes, often leading to lower limb amputations and even mortality. Stem cells have shown promise in promoting cutaneous wound healing by modulating inflammation, angiogenesis, and re‐epithelialization. However, more effective delivery and engraftment strategies are needed to prolong transplanted stem cell lifespan and their pro‐healing functions in a chronic wound environment to improve skin regeneration. In this study, an injectable poly(ethylene glycol) (PEG)–gelatin‐based hydrogel system is examined to create a functional stem cell niche for the delivery of adipose‐derived stem cells (ASCs) into diabetic wounds. Human ASCs are encapsulated into the in situ crosslinked hydrogels and cultured in a 3D topography. The encapsulated cells are well attached and spread inside the hydrogels, retaining viability, proliferation, and metabolic activity up to three weeks in vitro. Allogeneic ASCs are delivered to diabetic wounds by this hydrogel vehicle. It is found that stem cell retention is significantly improved in vivo with vehicle‐mediated delivery. The ASC‐hydrogel‐based treatment decreases inflammatory cell infiltration, enhances neovascularization, and remarkably accelerates wound closure in diabetic mice. Together, these findings suggest this conveniently‐applicable ASC‐hydrogel‐based skin substitute provides a promising potential for the treatment of chronic diabetic wounds.