Reactive Oxygen Species Shielding Hydrogel for the Delivery of Adherent and Nonadherent Therapeutic Cell Types<sup/>.
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-PDMA152-b-PNIPAAM225, 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 β-cell pseudo-islets against H2O2 toxicity. In sum, these results establish the potential of cytoprotective, thermogelling PDN biomaterials for injectable delivery of cell therapies.
['Dollinger|Bryan R|BR|', 'Gupta|Mukesh K|MK|', 'Martin|John R|JR|', 'Duvall|Craig L|CL|']
D000818:Animals D002448:Cell Adhesion D002452:Cell Count D016923:Cell Death D019610:Cytoprotection D006801:Humans D020100:Hydrogels D006861:Hydrogen Peroxide D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D051379:Mice D011108:Polymers D017382:Reactive Oxygen Species D012212:Rheology
hydrogel antioxidant cell-delivery thermoresponsive