title: Rapidly in situ forming biodegradable robust hydrogels by combining stereocomplexation and photopolymerization.
abstract: Our previous studies have shown that stereocomplexed hydrogels can be rapidly formed in vitro as well as in vivo upon mixing aqueous solutions of eight-arm poly(ethylene glycol)-poly(l-lactide) (PEG-PLLA) and poly(ethylene glycol)-poly(d-lactide) (PEG-PDLA) star block copolymers. In this study, stereocomplexation and photopolymerization are combined to yield rapidly in situ forming robust hydrogels. Two types of methacrylate-functionalized PEG-PLLA and PEG-PDLA star block copolymers, PEG-PLLA-MA and PEG-PDLA-MA, which have methacrylate groups at the PLA chain ends and PEG-MA/PLLA and PEG-MA/PDLA, which have methacrylate groups at the PEG chain ends, were designed and prepared. Results showed that stereocomplexed hydrogels could be rapidly formed (within 1-2 min) in a polymer concentration range of 12.5-17.5% (w/v), in which the methacrylate group hardly interfered with the stereocomplexation. When subsequently photopolymerized, these hydrogels showed largely increased storage moduli as compared to the corresponding hydrogels that were cross-linked by stereocomplexation or photopolymerization only. Interestingly, the storage modulus of stereocomplexed-photopolymerized PEG-PLA-MA hydrogels increased linearly with increasing stereocomplexation equilibration time prior to photopolymerization (from ca. 6 to 32 kPa), indicating that stereocomplexation aids in photopolymerization. Importantly, photopolymerization of stereocomplexed hydrogels could take place at very low initiator concentrations (0.003 wt %). Swelling/degradation studies showed that combining stereocomplexation and photopolymerization yielded hydrogels with prolonged degradation times as compared to corresponding hydrogels cross-linked by photopolymerization only (3 vs 1.5 weeks). Stereocomplexed-photopolymerized PEG-MA/PLA hydrogels degraded much slower than corresponding PEG-PLA-MA hydrogels, with degradation times ranging from 7 to more than 16 weeks. Therefore, combining stereocomplexation and photopolymerization is a novel approach to obtain rapidly in situ forming robust hydrogels.
authors.affiliation: Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, Institute for Biomedical Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Hiemstra
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Wouters
authors.forename: Jan
authors.initials: J
authors.lastname: Feijen
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D007773:Lactates / Q000138:chemical synthesis* / Q000737:chemistry; D008689:Methacrylates / Q000138:chemical synthesis* / Q000737:chemistry; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D012212:Rheology; D013237:Stereoisomerism
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D007773:Lactates; D008689:Methacrylates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols