Department of Materials, Imperial College London, SW7 2AZ London, UK.
Department of Frontier Materials, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan.
Acta Biomater. 2017 May;54:411-418. doi: 10.1016/j.actbio.2017.03.008. Epub 2017 Mar 8.
Hybrids that are molecular scale co-networks of organic and inorganic components are promising biomaterials, improving the brittleness of bioactive glass and the strength of polymers. Methacrylate polymers have high potential as the organic source for hybrids since they can be produced, through controlled polymerization, with sophisticated polymer architectures that can bond to silicate networks. Previous studies showed the mechanical properties of hybrids can be modified by polymer architecture and molar mass (MM). However, biodegradability is critical if hybrids are to be used as tissue engineering scaffolds, since the templates must be remodelled by host tissue. Degradation by-products have to either completely biodegrade or be excreted by the kidneys. Enzyme, or bio-degradation is preferred to hydrolysis by water uptake as it is expected to give a more controlled degradation rate. Here, branched and star shaped poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) (poly(MMA-co-TMSPMA)) were synthesized with disulphide based dimethacrylate (DSDMA) as a biodegradable branching agent. Biodegradability was confirmed by exposing the copolymers to glutathione, a tripeptide which is known to cleave disulphide bonds. Cleaved parts of the star polymer from the hybrid system were detected after 2weeks of immersion in glutathione solution, and MM was under threshold of kidney filtration. The presence of the branching agent did not reduce the mechanical properties of the hybrids and bone progenitor cells attached on the hybrids in vitro. Incorporation of the DSDMA branching agent has opened more possibilities to design biodegradable methacrylate polymer based hybrids for regenerative medicine.
Bioactive glasses can regenerate bone but are brittle. Hybrids can overcome this problem as intimate interactions between glass and polymer creates synergetic properties. Implants have previously been made with synthetic polymers that degrade by water, however, they degrade catastrophically, causing rapid loss of strength. Polymers that degrade by biological agents may degrade at a more controlled rate, which should give time for tissue repair and transfer of load. Previously, hybrids made with star shaped poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) (p(MMA-co-TMSPMA)) showed enhanced properties. However, methacrylates are not bio-degradable. Here, star shaped p(MMA-co-TMSPMA) was synthesized with a core that can be cleaved by glutathione, a tripeptide. On exposure to glutathione, the hybrid degraded, producing products with molecular weights below the kidney filtration threshold.
由有机和无机成分组成的分子级混合网络是很有前途的生物材料，可改善生物活性玻璃的脆性和聚合物的强度。甲基丙烯酸酯聚合物具有成为混合材料的有机来源的巨大潜力，因为可以通过受控聚合来生产它们，从而产生可以与硅酸盐网络结合的复杂聚合物结构。先前的研究表明，通过聚合物结构和摩尔质量（MM）可以修饰混合材料的机械性能。然而，如果混合材料要用作组织工程支架，则生物降解性至关重要，因为模板必须由宿主组织重塑。降解副产物必须完全生物降解或通过肾脏排出。由于预期酶或生物降解会比水合作用产生更受控的降解速率，因此，与通过水合作用吸收水相比，水解更可取。在这里，用二硫键基二甲基丙烯酸酯（DSDMA）作为可生物降解的支化剂合成了支化和星形聚（甲基丙烯酸甲酯-共-3-（三甲氧基甲硅烷基）丙基甲基丙烯酸酯）（聚（MMA-共-TMSPMA））。通过将共聚物暴露于谷胱甘肽（一种已知能切割二硫键的三肽）来确认生物降解性。在谷胱甘肽溶液中浸泡 2 周后，从杂交体系中的星形聚合物中检测到了被切割的部分，并且 MM 低于肾脏过滤的阈值。支化剂的存在并未降低混合材料的机械性能，并且体外附着在混合材料上的成骨祖细胞也没有受到影响。引入 DSDMA 支化剂为设计用于再生医学的可生物降解甲基丙烯酸酯聚合物基混合材料开辟了更多可能性。
生物活性玻璃可以再生骨骼，但易碎。混合材料可以克服这个问题，因为玻璃和聚合物之间的紧密相互作用创造了协同特性。先前已经用通过水降解的合成聚合物制造了植入物，但是，它们会灾难性地降解，导致强度迅速丧失。通过生物试剂降解的聚合物可能会以更受控的速率降解，这应该为组织修复和负载转移留出时间。先前，用星形聚（甲基丙烯酸甲酯-共-3-（三甲氧基甲硅烷基）丙基甲基丙烯酸酯）（p（MMA-co-TMSPMA））制成的混合材料显示出增强的性能。但是，甲基丙烯酸酯不可生物降解。在这里，用可以被谷胱甘肽（一种三肽）切割的核合成了星形 p（MMA-co-TMSPMA）。在暴露于谷胱甘肽后，混合材料降解，产生分子量低于肾脏过滤阈值的产物。
