Hiemstra Christine, Zhou Wei, Zhong Zhiyuan, Wouters Mariëlle, Feijen Jan
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.
J Am Chem Soc. 2007 Aug 15;129(32):9918-26. doi: 10.1021/ja072113p. Epub 2007 Jul 24.
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.
我们之前的研究表明，将八臂聚（乙二醇）-聚（L-丙交酯）（PEG-PLLA）和聚（乙二醇）-聚（D-丙交酯）（PEG-PDLA）星形嵌段共聚物的水溶液混合后，立体复合水凝胶能够在体外以及体内快速形成。在本研究中，将立体复合作用与光聚合作用相结合，以产生快速原位形成的坚固水凝胶。设计并制备了两种类型的甲基丙烯酸酯官能化的PEG-PLLA和PEG-PDLA星形嵌段共聚物，即PLA链端带有甲基丙烯酸酯基团的PEG-PLLA-MA和PEG-PDLA-MA，以及PEG链端带有甲基丙烯酸酯基团的PEG-MA/PLLA和PEG-MA/PDLA。结果表明，在聚合物浓度为12.5-17.5%（w/v）的范围内，立体复合水凝胶能够快速形成（在1-2分钟内），其中甲基丙烯酸酯基团几乎不干扰立体复合作用。当随后进行光聚合时，与仅通过立体复合或光聚合交联的相应水凝胶相比，这些水凝胶的储能模量大幅增加。有趣的是，立体复合-光聚合的PEG-PLA-MA水凝胶的储能模量随着光聚合前立体复合平衡时间的增加而线性增加（从约6 kPa增加到32 kPa），这表明立体复合有助于光聚合。重要的是，立体复合水凝胶的光聚合可以在非常低的引发剂浓度（0.003 wt%）下进行。溶胀/降解研究表明，与仅通过光聚合交联的相应水凝胶相比，将立体复合作用与光聚合作用相结合产生的水凝胶具有更长的降解时间（3周对1.5周）。立体复合-光聚合的PEG-MA/PLA水凝胶的降解速度比相应的PEG-PLA-MA水凝胶慢得多，降解时间为7至超过16周。因此，将立体复合作用与光聚合作用相结合是一种获得快速原位形成的坚固水凝胶的新方法。
