Application of Multi-Arm Poly (Ethylene Glycol) -Polylactide Copolymers as Biodegradable Soft Biomaterials

为探讨星形8臂聚乙二醇35k -b-聚l -丙交酯37K（8臂聚乙二醇35k -b- plla37k: PEG的M_n = 35000， PLLA的M_n = 37000）膜作为新型生物可吸收防黏附膜的潜力，研究了该水合膜的水结构、表面接触角、蛋白质吸附、细胞和血小板抗黏附性能。基于这些结果，我们发现8臂PEG35K-b-PLLA37K膜表现出生物惰性表面，这是由于大量的PEG链和膜表面的自由水层。这导致蛋白质吸收减少，细胞和血小板粘附在膜表面。这表明星形8臂PEG35K-b-PLLA37K膜可以作为一种新型的生物可吸收防粘膜。部分胆固醇取代的8臂聚乙二醇嵌段聚l-丙交酯（8臂peg -b- pla -胆固醇）是一种新型的星形可生物降解共聚物衍生物。两亲性的8臂PEG-b-PLLA-胆固醇水溶液（聚合物浓度大于3wt %）在34℃时表现出瞬时温度诱导的凝胶化，但无论浓度如何，未制备的8臂PEG-b-PLLA都没有发生凝胶化。此外，我们成功地创建了细胞外基质（ECM）样微米级网络结构，其孔隙度有利于水凝胶内细胞的三维增殖。这种网络结构主要归因于胆固醇组之间的特异性自组装。10%和20%的水凝胶在37℃的PBS中逐渐被侵蚀一个月，凝胶完全解离。此外，包封在水凝胶中的L929细胞由于具有类似ecm的网络结构，能够在水凝胶内存活并三维增殖。因此，体外细胞培养研究表明，8臂peg -b- pla -胆固醇是一种有希望的新型可注射细胞支架。

To explore the potential of a star-shaped 8-arms poly(ethylene glycol)35K-b-poly(L-lactide)37K (8-arms PEG35K-b-PLLA37K: M_n of PEG=35,000, M_n of PLLA=37,000) film as a novel bioabsorbable adhesion-prevention membrane, water structure, surface contact angle, protein adsorption, and cell and platelet anti-adhesion properties of such a hydrated film were investigated. Based on these results, it was found that the 8-arms PEG35K-b-PLLA37K film exhibited a biologically inert surface, which was the result of a large number of PEG chains and a free water layer on the film surface. This led to a reduction in protein absorption and cell and platelet adhesion onto the film surface. This implies the star-shaped 8-arms PEG35K-b-PLLA37K film can be utilized as a novel bioabsorbable adhesion-prevention membrane.Partially cholesterol-substituted 8-arm poly(ethylene glycol)-block-poly(L-lactide) (8-arm PEG-b-PLLA-cholesterol) was prepared as a novel star-shaped, biodegradable copolymer derivative. The amphiphilic 8-arm PEG-b-PLLA-cholesterol aqueous solution (polymer concentration, above 3 wt%) exhibited instantaneous temperature-induced gelation at 34℃, but the virgin 8-arm PEG-b-PLLA did not, irrespective of concentration. Moreover, we successfully created an extracellular matrix (ECM)-like micrometer-scale network structure with favorable porosity for 3D proliferation of cells inside the hydrogel. This network structure was mainly attributed to specific self-assembly between cholesterol groups. The 10 and 20 wt% hydrogels were eroded gradually in PBS at 37℃ over the course of a month, and the gel became completely dissociated. Moreover, the L929 cells encapsulated into the hydrogel were viable and proliferated 3-dimensionally inside the hydrogels as a result of the ECM-like network structure. Thus, in vitro cell culture studies demonstrated that 8-arm PEG-b-PLLA-cholesterol is a promising candidate as a novel injectable cell scaffold.