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Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis
- Source :
- Acta biomaterialia. 51
- Publication Year :
- 2016
-
Abstract
- Adipose-derived stem cells (ASCs) secrete several angiogenic growth factors and can be applied to treat ischemic tissue. However, transplantation of dissociated ASCs has frequently resulted in rapid cell death. Therefore, we aimed to develop a thermosensitive chitosan/gelatin hydrogel that is capable of ASC sustained release for therapeutic angiogenesis. By blending gelatin in the chitosan thermosensitive hydrogel, we significantly enhanced the viability of the encapsulated ASCs. During in vitro culturing, the gradual degradation of gelatin led to sustained release of ASCs from the chitosan/gelatin hydrogel. In vitro wound healing assays revealed significantly faster cell migration by co-culturing fibroblasts with ASCs encapsulated in chitosan/gelatin hydrogel compared to pure chitosan hydrogels. Additionally, significantly higher concentrations of vascular endothelial growth factor were found in the supernatant of ASC-encapsulated chitosan/gelatin hydrogels. Co-culturing SVEC4-10 endothelial cells with ASC-encapsulated chitosan/gelatin hydrogels resulted in significantly more tube-like structures, indicating the hydrogel’s potential in promoting angiogenesis. Chick embryo chorioallantoic membrane assay and mice wound healing model showed significantly higher capillary density after applying ASC-encapsulated chitosan/gelatin hydrogel. Relative to ASC alone or ASC-encapsulated chitosan hydrogel, more ASCs were also found in the wound tissue on post-wounding day 5 after applying ASC-encapsulated chitosan/gelatin hydrogel. Therefore, chitosan/gelatin thermosensitive hydrogels not only maintain ASC survival, they also enable sustained release of ASCs for therapeutic angiogenesis applications, thereby exhibiting great clinical potential in treating ischemic diseases. Statement of Significance Adipose-derived stem cells (ASCs) exhibit great potential to treat ischemic diseases. However, poor delivery methods lead to low cellular survival or dispersal of cells from target sites. In this study, we developed a thermosensitive chitosan/gelatin hydrogel that not only enhances the viability of the encapsulated ASCs, the gradual degradation of gelatin also result in a more porous architecture, leading to sustained release of ASCs from the hydrogel. ASC-encapsulated hydrogel enhanced in vitro wound healing of fibroblasts and tube formation of endothelial cells. It also promoted in vivo angiogenesis in a chick embryo chorioallantoic membrane assay and a mice wound model. Therefore, chitosan/gelatin hydrogel represents an effective delivery system that allows for controlled release of viable ASCs for therapeutic angiogenesis.
- Subjects :
- 0301 basic medicine
Adult
Male
animal structures
Materials science
food.ingredient
Biomedical Engineering
Neovascularization, Physiologic
macromolecular substances
02 engineering and technology
Chick Embryo
Biochemistry
Gelatin
Biomaterials
Chitosan
03 medical and health sciences
chemistry.chemical_compound
food
Animals
Humans
Therapeutic angiogenesis
Molecular Biology
Tube formation
Stem Cells
technology, industry, and agriculture
hemic and immune systems
Cell Differentiation
Hydrogels
General Medicine
Middle Aged
021001 nanoscience & nanotechnology
Controlled release
eye diseases
Cell biology
Transplantation
030104 developmental biology
chemistry
Adipose Tissue
Self-healing hydrogels
Heterografts
Female
0210 nano-technology
Wound healing
Biotechnology
Biomedical engineering
Stem Cell Transplantation
Subjects
Details
- ISSN :
- 18787568
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- Acta biomaterialia
- Accession number :
- edsair.doi.dedup.....1547405a0191ef2a684b6c26ed3972c0