Wang Bing, Dong Jun, Li Qijie, Xiong Zuochun, Xiong Chengdong, Chen Dongliang
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, China; Department of Polymer Chemistry and Physics, University of Chinese Academy of Sciences, Beijing, China.
J Biomed Mater Res A. 2014 Nov;102(11):4062-70. doi: 10.1002/jbm.a.35077. Epub 2014 Jan 17.
Fibroblast plays an important role in the occurrence of postoperative tissue adhesion; materials that have particular "cell-material" interactions to inhibit proliferation of fibroblast will be excellent potential adhesion barriers. In the current study, we synthesized copolymers of p-dioxanone and L-phenylalanine (PDPA) and evaluated the mechanism of its particular inhibition effect on L929 fibroblast proliferation when used as a culture surface. PDPA electrospun membranes could induce apoptosis of L929 fibroblasts. We hypothesized there were two reasons for the apoptosis induction: one was the ability to facilitate cell adhesion of materials, and the other was production of the degradation product, L-phenylalanine. Ninhydrin colorimetric results revealed that L-phenylalanine was continuously released during the culture process and could induce apoptosis in L929 cells. Relatively poor cell adhesion and constant release of L-phenylalanine made PDPA-1 to be the most efficient polymer for the induction of apoptosis. Analysis of apoptosis-related genes revealed that PDPA-induced apoptosis might be performed in a mitochondrial-dependent pathway. But poly(p-dioxanone)-induced apoptosis might occur in a c-Myc independent pathway that was different from PDPA.
成纤维细胞在术后组织粘连的发生中起重要作用;具有特殊“细胞-材料”相互作用以抑制成纤维细胞增殖的材料将是极具潜力的粘连屏障。在本研究中,我们合成了对二氧环己酮与L-苯丙氨酸的共聚物(PDPA),并评估了其作为培养表面时对L929成纤维细胞增殖的特殊抑制作用机制。PDPA静电纺丝膜可诱导L929成纤维细胞凋亡。我们推测凋亡诱导有两个原因:一是材料促进细胞粘附的能力,另一个是降解产物L-苯丙氨酸的产生。茚三酮比色法结果显示,L-苯丙氨酸在培养过程中持续释放,并可诱导L929细胞凋亡。相对较差的细胞粘附性和L-苯丙氨酸的持续释放使PDPA-1成为诱导凋亡最有效的聚合物。凋亡相关基因分析表明,PDPA诱导的凋亡可能通过线粒体依赖途径进行。但聚对二氧环己酮诱导的凋亡可能通过与PDPA不同的c-Myc非依赖途径发生。