title: Degradable, thermo-sensitive poly(N-isopropyl acrylamide)-based scaffolds with controlled porosity for tissue engineering applications.
abstract: We have developed a thermoresponsive poly(N-isopropyl acrylamide)-based scaffold with degradability and controlled porosity. Biodegradable poly(N-isopropyl acrylamide) hydrogels were synthesized by photocopolymerization of N-isopropylacrylamide with 2-methylene-1,3-dioxepane and polycaprolactone dimethacrylate. The hydrogels' phase transition temperature, swelling, and viscoelastic properties, as well as hydrolytic degradability at 25 and 37 °C, were explored. A sphere-templating technique was applied to fabricate hydrogel scaffolds with controllable pore size and a highly interconnected porous structure. The scaffold pore diameter change as a function of temperature was evaluated and, as expected, pores decreased in diameter when the temperature was raised to 37 °C. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test results suggested neither the scaffolds nor their degradation products were cytotoxic to NIH3T3 cells. Scaffolds with 55 ± 5 μm pore diameter were loaded with NIH3T3 cells and then were warmed to 37 °C entrapping cells in pores approximately 39 μm in diameter, a size range we have found to be optimal for angiogenesis and biointegration. Cells showed uniform infiltration and an elongated morphology after 7 days of culture. Due to the controlled monodisperse pore diameter, highly interconnected architecture, fully degradable chemistry and thermoresponsive properties, the polyNIPAM-based scaffolds developed here are attractive for applications in tissue engineering.
authors.affiliation: University of Washington, 1705 Northeast Pacific Street, Seattle, WA 98195, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Galperin
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Long
authors.forename: Buddy D
authors.initials: BD
authors.lastname: Ratner
mesh_terms: D000178:Acrylamides / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D000180:Acrylic Resins; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D020100:Hydrogels; D051379:Mice; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D011108:Polymers / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D016062:Porosity; D012212:Rheology; D013499:Surface Properties; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D000178:Acrylamides; D000180:Acrylic Resins; D001672:Biocompatible Materials; D020100:Hydrogels; D011108:Polymers; C052970:poly-N-isopropylacrylamide