Biocompatible wound dressings based on chemically degradable triblock copolymer hydrogels

被引:132
作者
Madsen, Jeppe [1 ]
Armes, Steven P. [1 ]
Bertal, Karima [2 ]
Lomas, Hannah [2 ]
MacNeil, Sheila [2 ]
Lewis, Andrew L. [3 ]
机构
[1] Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England
[2] Univ Sheffield, Dept Mat Engn, Kroto Res Inst, Sheffield S3 7HQ, S Yorkshire, England
[3] Biocompatibles UK Ltd, Chapman House, Surrey GU9 8QL, England
关键词
D O I
10.1021/bm8005006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The synthesis of a series of thermo-responsive ABA triblock copolymers in which the outer A blocks comprise poly(2-hydroxypropyl methacrylate) and the central B block is poly(2-(methacryloyloxy) ethyl phosphorylcholine) is achieved using atom transfer radical polymerization. These novel triblock copolymers form thermo-reversible physical gels with critical gelation temperatures and mechanical properties that are highly dependent on the copolymer composition and concentration. TEM studies on dried dilute copolymer solutions indicate the presence of colloidal aggregates, which is consistent with micellar gel structures. This hypothesis is consistent with the observation that incorporating a central disulfide bond within the B block leads to thermo-responsive gels that can be efficiently degraded using mild reductants such as dithiothreitol (DTT) over time scales of minutes at 37 degrees C. Moreover, the rate of gel dissolution increases at higher DTT/disulfide molar ratios. Finally, these copolymer gels are shown to be highly biocompatible. Only a modest reduction in proliferation was observed for monolayers of primary human dermal fibroblasts, with no evidence for cytotoxicity. Moreover, when placed directly on 3D tissue-engineered skin, these gels had no significant effect on cell viability. Thus, we suggest that these thermo-responsive biodegradable copolymer gels may have potential applications as wound dressings.
引用
收藏
页码:2265 / 2275
页数:11
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