期刊
TISSUE ENGINEERING PART A
卷 23, 期 19-20, 页码 1120-1131出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2016.0495
关键词
antioxidant; cell-delivery; hydrogel; thermoresponsive
资金
- NIH [CA68485, DK20593, DK58404, HD1502, DK59637, Ey008126]
- National Institute of Health Integrated Training in Engineering and Diabetes Training Grant [NIH 1T32DK101003-01A1]
- National Science Foundation CAREER Award (DMR) [BMAT 1349604]
Cell therapies suffer from poor survival post-transplant due to placement into hostile implant sites characterized by host immune response and innate production of high levels of reactive oxygen species (ROS). We hypothesized that cellular encapsulation within an injectable, antioxidant hydrogel would improve viability of cells exposed to high oxidative stress. To test this hypothesis, we applied a dual thermo-and ROS-responsive hydrogel comprising the ABC triblock polymer poly[(propylene sulfide)-block-(N,N-dimethyl acrylamide)-block-(N-isopropylacrylamide)] (PPS135-b-PDMA(152)-b-PNIPAAM(225), PDN). The PPS chemistry reacts irreversibly with ROS such as hydrogen peroxide (H2O2), imparting inherent antioxidant properties to the system. Here, PDN hydrogels were successfully integrated with type 1 collagen to form ROS-protective, composite hydrogels amenable to spreading and growth of adherent cell types such as mesenchymal stem cells (MSCs). It was also shown that, using a control hydrogel substituting nonreactive polycaprolactone in place of PPS, the ROS-reactive PPS chemistry is directly responsible for PDN hydrogel cytoprotection of both MSCs and insulin-producing beta-cell pseudo-islets against H2O2 toxicity. In sum, these results establish the potential of cytoprotective, thermogelling PDN biomaterials for injectable delivery of cell therapies.
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