Novel biodegradable polyphosphate cross-linker for making biocompatible hydrogel

Novel biodegradable polyphosphate cross-linker for making biocompatible hydrogel
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DOI:
10.1021/bm049961m
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发表时间:
2004-05-01
期刊:
影响因子:
6.2
通讯作者:
Akiyoshi, K
Akiyoshi, K
中科院分区:
化学2区
文献类型:
--
作者:
Iwasaki, Y;Nakagawa, C;Akiyoshi, K

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为获得一种新型可生物降解交联剂,以2-(2-氧-1,3,2-二氧磷膦烷)和2-(2-氧-1,3,2-二氧磷酰氧乙基甲基丙烯酸酯)(OPEMA)为原料,通过开环聚合合成了可聚合聚磷酸酯(PIOP)。PIOP的平均分子量为1.2 × 10(4),一个PIOP分子中OPEMA单位数为2.2。在不同pH的水介质中评估了PIOP的非酶降解。水解程度与pH值有关;也就是说,它随着培养基pH值的增加而增加。在pH为11.0时,PIOP仅在6天内完全降解。采用自由基聚合法制备了与PIOP交联的聚[2-甲基丙烯酰氧乙基磷酸胆碱(MPC)]。该聚合物可形成水凝胶,且水凝胶中游离水含量高。胰蛋白酶在水凝胶中的酶活性与在缓冲液中的酶活性相似。水凝胶对胰蛋白酶的功能无不良影响。用v79细胞评价聚(MPC)和降解PIOP的细胞毒性,两种情况下均未观察到。综上所述,PIOP是一种可水解的聚合物,可作为交联剂使用,高分子聚合物(MPC)与PIOP交联制备出具有生物可降解性和生物相容性的新型水凝胶。
To obtain a novel biodegradable cross-linker, polymerizable polyphosphate (PIOP) was synthesized by ringopening polymerization of 2-i-propyl-2-oxo-1,3,2-dioxaphospholane with 2-(2-oxo-1,3,2-dioxaphosphoroyloxyethyl methacrylate) (OPEMA). The number averaged molecular weight of the PIOP was 1.2 x 10(4), and the number of OPEMA units in one PIOP molecule was 2.2. Nonenzymatic degradation of the PIOP was evaluated in various pH aqueous media. The degree of hydrolysis was dependent on the pH; that is, it increased with an increase in the pH of the medium. At pH 11.0, the PIOP completely degraded in only 6 days. The poly [2-methacryloyloxyethyl phosphorylcholine (MPC)] cross-linked with the PIOP was prepared by radical polymerization. This polymer could form hydrogel, and the free water fraction in the hydrogel was high. The enzymatic activity of trypsin in contact with the hydrogel was similar to that in buffer solution. There is no adverse effect caused by the hydrogel to reduce the function of the trypsin. The cytotoxicity of poly(MPC) and degraded PIOP was evaluated using v79 cells, and it was not observed in either case. In conclusion, PIOP is a hydrolyzable polymer, which can be used as a cross-linker, and novel hydrogels having biodegradability and biocompatibility were prepared from poly(MPC) cross-linked with the PIOP.