Biomaterial Engineering for Medical and Health Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok 10330, Thailand.
Biomaterial Engineering for Medical and Health Research Unit, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Int J Biol Macromol. 2022 Sep 1;216:437-445. doi: 10.1016/j.ijbiomac.2022.07.011. Epub 2022 Jul 7.
Flexible films were prepared from silk fibroin (SF) and gelatin (GA) with a presence of glycerol (Gly), followed by water vapor annealing to achieve water-insoluble matrices. The blended SF/GA/Gly films were chemically conjugated with tobacco mosaic virus (TMV), either native (TMV-wt) or genetically modified with Arg-Gly-Asp (RGD) sequences (TMV-rgd), to improve cellular responses. The attachment and proliferation of L929 cells on TMV-decorated films were improved, possibly due to enhanced surface roughness. The cellular responses were pronounced with TMV-rgd, due to the proper decoration of RGD, which is an integrin recognition motif supporting cell binding. However, the biological results were inconclusive for human primary cells because of an innate slow growth kinetic of the cells. Additionally, the cells on SF/GA/Gly films were greater populated in S and G2/M phase, and the cell cycle arrest was notably increased in the TMV-conjugated group. Our findings revealed that the films modified with TMV were cytocompatible and the cellular responses were significantly enhanced when conjugated with its RGD mutants. The biological analysis on the cellular mechanisms in response to TMV is further required to ensure the safety concern of the biomaterials toward clinical translation.
采用丝素蛋白（SF）和明胶（GA）为原料，通过添加甘油（Gly）制备了具有水蒸气退火处理的不溶性水基薄膜。然后将该混合 SF/GA/Gly 薄膜通过化学方法与烟草花叶病毒（TMV）结合，TMV 可以是天然的（TMV-wt），也可以是经过精氨酸-甘氨酸-天冬氨酸（RGD）序列修饰的（TMV-rgd），以提高细胞反应。由于表面粗糙度增加，经 TMV 修饰的薄膜可以提高 L929 细胞的黏附和增殖能力。由于 RGD 的适当修饰，TMV-rgd 可以增强细胞结合，从而导致细胞反应更为显著。然而，由于细胞的固有生长动力学较慢，对于原代人细胞，生物实验结果并不明确。此外，SF/GA/Gly 薄膜上的细胞更倾向于 S 和 G2/M 期，而在 TMV 结合组中，细胞周期阻滞明显增加。我们的研究结果表明，经 TMV 修饰的薄膜具有细胞相容性，当与 RGD 突变体结合时，细胞反应显著增强。需要进一步进行细胞机制的生物学分析，以确保生物材料向临床转化的安全性。
