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Acta Biomater. 2015 Oct;25:291-303. doi: 10.1016/j.actbio.2015.07.042. Epub 2015 Jul 30.

Preformed gelatin microcryogels as injectable cell carriers for enhanced skin wound healing.

Author information

1
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
2
Division of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
3
Center 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 100005, China.
4
School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
5
Division of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China. Electronic address: xjwang100@hotmail.com.
6
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China. Electronic address: duyanan@tsinghua.edu.cn.
7
Center 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 100005, China; Center of Translational Medicine Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China. Electronic address: zhaochunhua@vip.163.com.

Abstract

Wound dressings of cell-laden bulk hydrogel or scaffold were mainly applied for enhanced cell engraftment in contrast to free cell injection. However, dressing of cells laden in biomaterials on wound surface might not effectively and timely exert functions on deep or chronic wounds where insufficient blood supply exists. Previously, we developed injectable gelatin microcryogels (GMs) which could load cells for enhanced cell delivery and cell therapy. In this study, biological changes of human adipose-derived stem cells (hASCs) laden in GMs were compared in varied aspects with traditional two dimensional (2D) cell culture, such as cell phenotype markers, stemness genes, differentiation, secretion of growth factors, cell apoptosis and cell memory by FACS, QRT-PCR and ELISA, that demonstrated the priming effects of GMs on upregulation of stemness genes and improved secretion of growth factors of hASCs for potential augmented wound healing. In a full-thickness skin wound model in nude mice, multisite injection and dressing of hASCs-laden GMs could significantly accelerate the healing compared to free cell injection. Bioluminescence imaging and protein analysis indicated improved cell retention and secretion of multiple growth factors. Our study suggests that GMs as primed injectable 3D micro-niches represent a new cell delivery methodology for skin wound healing which could not only benefit on the recovery of wound bed but also play direct effects on wound basal layer for healing enhancement. Injectable GMs as facile multisite cell delivery approach potentially provide new minimally-invasive therapeutic strategy for refractory wounds such as diabetic ulcer or radiative skin wound.

STATEMENT OF SIGNIFICANCE:

This work applied a type of elastic micro-scaffold (GMs) to load and prime hMSCs for skin wound healing. Due to the injectability of GMs, the 3D cellular micro-niches could simply realize minimally-invasive and multisite cell delivery approach for accelerating the wound healing process superior to free cell injection. The biological features of MSCs has been thoroughly characterized during 3D culture in GMs (i.e. cell proliferation, characterization of cell surface markers, stemness of MSCs in GMs, differentiation of MSCs in GMs, secretion of MSCs in GMs, induced apoptosis of MSCs in GMs). Multiple methods such as bioluminescent imaging, immunohistochemistry, immunofluorescence, qRT-PCR, ELSA and western blot were used to assess the in vivo results between groups.

KEYWORDS:

Adipose-derived stromal/stem cells; Gelatin microcryogels; Injectable; Skin wound healing

PMID:
26234487
DOI:
10.1016/j.actbio.2015.07.042
[Indexed for MEDLINE]

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