A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer.
A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer.
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DOI：
10.1016/j.biomaterials.2010.09.044
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发表时间：
2011-01
期刊：
影响因子：
14
通讯作者：
Wang, Yadong
中科院分区：
文献类型：
--
作者：
Park, Daewon;Wu, Wei;Wang, Yadong
可注射反向热凝胶作为组织工程和药物释放的生物材料具有很大的潜力。然而，大多数现有的凝胶缺乏可用生物分子修饰的官能团，这些官能团可以引导细胞/材料相互作用。我们创造了一种胺功能化的ABA嵌段共聚物，聚乙二醇聚(丝氨醇六亚甲基氨酯)，或ESHU。这种反向热凝胶由疏水嵌段(B)：聚(六亚甲基丝氨酸乙二醇酯)和亲水嵌段(A)：聚乙二醇组成。用凝胶渗透色谱(GPC)、傅里叶变换红外光谱(FTIR)和核磁共振氢谱(1HFT核磁共振)对聚合物进行了表征。流变学研究表明，ESHU在磷酸盐缓冲液中在32℃开始相变，在37℃达到最大弹性模量。在PBS和胆固醇酯酶溶液中的体外降解实验表明，聚合物是可水解的，胆固醇酯酶的存在极大地促进了水解。体外细胞毒性实验表明，ESHU具有良好的细胞相容性和细胞活力，与经组织培养处理的聚苯乙烯没有区别。大鼠皮下种植早期表现出较好的耐受性，早期有中等的ED-1阳性巨噬细胞，在植入后4周基本消失。我们用六肽Ile-Lys-Val-Ala-Val-Ser(IKVAVS)对ESHU进行官能化，这种六肽在体温下能迅速凝胶化。我们期待这一可功能化反向热凝胶的新平台在组织工程和再生医学中提供多功能的生物材料。
Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and 1H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32°C and reached maximum elastic modulus at 37°C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine.
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