Multidisciplinary Research Center, Shantou University, Guangdong 515063, China.
Acta Biomater. 2013 Aug;9(8):7845-54. doi: 10.1016/j.actbio.2013.04.038. Epub 2013 Apr 29.
Polyhydroxyalkanoates (PHAs) belong to a family of copolyesters with demonstrated biocompatibility. We hypothesize that genetically fusing evolutionarily preserved cell binding motifs, such as RGD or IKVAV, to the PHA-binding protein phasin (PhaP) for surface functionalization of PHA materials could better support the growth and differentiation of neural stem cells (NSCs). This hypothesis is tested on three polyester materials of the same aliphatic family: poly(L-lactic acid) (PLA) and two PHB copolymers, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBVHHx). Experimental results indicate that surface coating of the two fusion proteins, PhaP-RGD and PhaP-IKVAV, provides short-term advantages in promoting the adhesion, proliferation and neural differentiation of rat NSCs compared to the PhaP-coated or uncoated material. Among the tested samples, the combination of coating PhaP-IKVAV on an PHBVHHx surface yields the highest levels in cell adhesion and proliferation, while the PLA film coated with PhaP-IKVAV promotes better neural differentiation and neurite outgrowth in the early stage. Because both PhaP-RGD and PhaP-IKVAV could be produced in an inexpensive manner, our data suggest that PhaP-IKVAV is an ideal nonspecific coating agent to functionalize hydrophobic biomaterials in the application of neural tissue engineering.
聚羟基烷酸酯 (PHA) 属于一类具有生物相容性的共聚酯。我们假设，通过将进化上保守的细胞结合基序（如 RGD 或 IKVAV）基因融合到 PHA 结合蛋白（PhaP）上，对 PHA 材料进行表面功能化，可以更好地支持神经干细胞 (NSC) 的生长和分化。这一假设在三种具有相同脂肪族家族的聚酯材料上进行了测试：聚（L-乳酸）（PLA）和两种 PHB 共聚物，聚（3-羟基丁酸酯-co-3-羟基己酸酯）和聚（3-羟基丁酸酯-co-3-羟基戊酸酯-co-3-羟基己酸酯）（PHBVHHx）。实验结果表明，与 PhaP 涂层或未涂层材料相比，两种融合蛋白（PhaP-RGD 和 PhaP-IKVAV）的表面涂层在促进大鼠 NSC 的粘附、增殖和神经分化方面提供了短期优势。在测试的样品中，将 PhaP-IKVAV 涂层涂覆在 PHBVHHx 表面上，可实现最高的细胞粘附和增殖水平，而涂覆有 PhaP-IKVAV 的 PLA 薄膜则可促进神经分化和早期神经突生长。由于 PhaP-RGD 和 PhaP-IKVAV 都可以以廉价的方式生产，我们的数据表明，PhaP-IKVAV 是一种理想的非特异性涂层剂，可用于对神经组织工程应用中的疏水性生物材料进行功能化。
