title: Reactive Oxygen Species Shielding Hydrogel for the Delivery of Adherent and Nonadherent Therapeutic Cell Types<sup/>.
abstract: 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 H2O2toxicity. In sum, these results establish the potential of cytoprotective, thermogelling PDN biomaterials for injectable delivery of cell therapies.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University , Nashville, Tennessee.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Dollinger
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University , Nashville, Tennessee.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Gupta
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University , Nashville, Tennessee.
authors.forename: John R
authors.initials: JR
authors.lastname: Martin
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University , Nashville, Tennessee.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Duvall
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000633:toxicity*; D012212:Rheology
chemical_list: D020100:Hydrogels; D011108:Polymers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: antioxidant; cell-delivery; hydrogel; thermoresponsive