Rapidly in situ forming biodegradable robust hydrogels by combining stereocomplexation and photopolymerization

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.