title: Photopolymerized thermosensitive hydrogels: synthesis, degradation, and cytocompatibility.
abstract: In situ forming hydrogels based on thermosensitive polymers have attractive properties for tissue engineering. However, the physical interactions in these hydrogels are not strong enough to yield gels with sufficient stability for many of the proposed applications. In this study, additional covalent cross-links were introduced by photopolymerization to improve the mechanical properties and the stability of thermosensitive hydrogels. Methacrylate groups were coupled to the side chains of triblock copolymers (ABA) with thermosensitive poly( N-(2-hydroxypropyl) methacrylamide lactate) A blocks and a hydrophilic poly(ethylene glycol) B block. These polymers exhibit lower critical solution temperature (LCST) behavior in aqueous solution and the cloud point decreased with increasing amounts of methacrylate groups. These methacrylate groups were photopolymerized above the LCST to render covalent cross-links within the hydrophobic domains. The mechanical properties of photopolymerized hydrogels were substantially improved and their stability was prolonged significantly compared to nonphotopolymerized hydrogels. Whereas non-UV-cured gels disintegrated within 2 days at physiological pH and temperature, the photopolymerized gels degraded in 10 to 25 days depending on the degree of cross-linking. To assess biocompatibility, goat mesenchymal stem cells were seeded on the hydrogel surface or encapsulated within the gel and they remained viable as demonstrated by a LIVE/DEAD cell viability/cytotoxicity assay. Expression of alkaline phosphatase and production of collagen I demonstrated the functionality of the mesenchymal stem cells and their ability to differentiate upon encapsulation. Due to the improved mechanical properties, stability, and adequate cytocompatibility, the photopolymerized thermosensitive hydrogels can be regarded as highly potential materials for applications in tissue engineering.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands. T.Vermonden@uu.nl
authors.forename: Tina
authors.initials: T
authors.lastname: Vermonden
authors.forename: Natalja E
authors.initials: NE
authors.lastname: Fedorovich
authors.forename: Daphne
authors.initials: D
authors.lastname: van Geemen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Alblas
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018786:Bone Substitutes; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism; D006041:Goats; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007773:Lactates / Q000737:chemistry; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012212:Rheology; D013696:Temperature; D023822:Tissue Engineering; D014466:Ultraviolet Rays
chemical_list: D000178:Acrylamides; D001672:Biocompatible Materials; D018786:Bone Substitutes; D024042:Collagen Type I; D020100:Hydrogels; D007773:Lactates; D011108:Polymers; C509680:poly(N-(2-hydroxypropyl) methacrylamide lactate); D011092:Polyethylene Glycols; D000469:Alkaline Phosphatase