Enhanced Wound Healing by Human Adipose-derived Stem Cells and Gelatin Microcryogels in a Nude Mice Model
Lin Zhu, MD1, Yang Zeng, PhD2, Qin Han, PhD3, Wei Liu, PhD2, Xiaojing Mao, MD3, Yaqian Li, MD2,4, Nanze Yu, MD1, Siyu Feng, PhD4, Qinyouen Fu, PhD4, Xiaojun Wang, MD1, Yanan Du, PhD2, Robert Chunhua Zhao, PhD3.
1Department of Surgery, Division of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China, 2Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, 3Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 4School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
PURPOSE: Advances in the development of biomaterial assisted cell therapy have elevated locally cell delivery methods to augment cell therapeutic effects for skin wound. Cell loaded bulk hydrogel or scaffold dressings were mainly applied for enhanced cell engraftment in contrast to traditional single cell injection. Previously, we developed injectable gelatin microcryogels (GMs) which could prime mesenchymal stem cells (MSCs) for enhanced cell protection and cell retention in vivo.METHODS: Stemness and growth factors secretion of human MSCs (hMSCs) with GMs were compared to traditional cells in vitro. An excisonal wound healing model was used to compare the ability of hMSCs-GMs constructs versus hMSCs alone to accelerate wound healing.RESULTS: Stemness and growth factors secretion of hMSCs were found significantly improved in GMs compared to traditional cells in vitro. GMs could protect cells from apoptosis in a mimetic inflammatory environment. Multisite injection and dressing of hMSCs laden GMs could significantly enhance full-thickness skin wound healing in nude mice compared to solely hMSCs injection by enhanced cell retention and growth factor secretion. CONCLUSION: Injectable GMs could boost MSCs healing function for skin wound. Meanwhile, injectable GMs as facile multisite cell delivery approach might provide new minimally-invasive therapeutic strategy for refractory wounds such as diabetic ulcer or radiative skin wound.
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