Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
Biomaterials. 2010 Mar;31(9):2453-60. doi: 10.1016/j.biomaterials.2009.11.115. Epub 2009 Dec 22.
In situ-forming gel systems have drawn increasing attention for their potential use in a variety of biomedical applications. Here, we examined an in situ-forming gel system comprised of MPEG-b-PCL and MPEG-b-(PCL-ran-PLLA) diblock copolymers with different PLLA contents (0-10 mol%) in the PCL segment. The crystalline region of the PCL-ran-PLLA segment decreased with increasing PLLA content. The MPEG-b-(PCL-ran-PLLA) diblock copolymer solutions were liquid at room temperature and only MPEG-b-(PCL-ran-PLLA) diblock copolymer solutions with a PLLA content < or = 5 mol% in the PCL segment showed a sol-to-gel transition as the temperature was increased. The viscosity change associated with sol-to-gel phase transition depended on the PLLA content in the PCL segment. A MPEG-b-PCL diblock copolymer solution incubated in vitro showed increasing viscosity without degradation, whereas the viscosity of MPEG-b-(PCL-ran-PLLA) diblock copolymer solutions continuously and sharply decreased with increasing PLLA content in the PCL segment. As the amount of PLLA increased, the size of in vivo-formed MPEG-b-(PCL-ran-PLLA) gels after initial injection tended to gradually decrease because of hydrolytic degradation of the PLLA in the PCL-ran-PLLA segment. An immunohistochemical examination showed that in vivo MPEG-b-(PCL-ran-PLLA) diblock copolymer gels provoked only a modest inflammatory response. Collectively, our results show that the MPEG-b-(PCL-ran-PLLA) diblock copolymer gel described here could serve as a minimally invasive, therapeutic, in situ-forming gel system that offers an experimental window adjustable from a few weeks to a few months.
原位形成凝胶系统因其在各种生物医学应用中的潜在用途而受到越来越多的关注。在这里，我们研究了一种由 MPEG-b-PCL 和 MPEG-b-(PCL-ran-PLLA) 两亲性嵌段共聚物组成的原位形成凝胶系统，其中 PCL 段中的 PLLA 含量（0-10mol%）不同。PCL-ran-PLLA 段的结晶区随 PLLA 含量的增加而减少。室温下 MPEG-b-(PCL-ran-PLLA) 两亲性嵌段共聚物溶液为液态，只有 PCL 段中 PLLA 含量≤5mol%的 MPEG-b-(PCL-ran-PLLA) 两亲性嵌段共聚物溶液在升高温度时才表现出溶胶-凝胶转变。与溶胶-凝胶相转变相关的粘度变化取决于 PCL 段中的 PLLA 含量。在体外孵育的 MPEG-b-PCL 两亲性嵌段共聚物溶液显示出粘度增加而没有降解，而 MPEG-b-(PCL-ran-PLLA) 两亲性嵌段共聚物溶液的粘度随 PCL 段中 PLLA 含量的增加而连续且急剧下降。随着 PLLA 含量的增加，初始注射后体内形成的 MPEG-b-(PCL-ran-PLLA) 凝胶的尺寸由于 PCL-ran-PLLA 段中 PLLA 的水解降解而逐渐减小。免疫组织化学检查显示，体内 MPEG-b-(PCL-ran-PLLA) 两亲性嵌段共聚物凝胶仅引起适度的炎症反应。总的来说，我们的结果表明，这里描述的 MPEG-b-(PCL-ran-PLLA) 两亲性嵌段共聚物凝胶可以作为一种微创、治疗性的原位形成凝胶系统，提供一个可调节的实验窗口，从几周到几个月不等。
