Abstract:
Reliable in vitro models closely resembling native tissue are urgently needed for disease modeling and drug screening applications. Recently, conductive biomaterials have received increasing attention in the development of in vitro models as they permit exogenous electrical signals to guide cells toward a desired cellular response. Interestingly, they have demonstrated that they promote cellular proliferation and adhesion even without external electrical stimulation. This paper describes the development of a conductive, fully synthetic hydrogel based on hybrids of the peptide-modified polyisocyanide (PIC-RGD) and the relatively conductive poly(aniline-co-N-(4-sulfophenyl)aniline) (PASA) and its suitability as the in vitro matrix. We demonstrate that incorporating PASA enhances the PIC-RGD hydrogel\'s electroactive nature without significantly altering the fibrous architecture and nonlinear mechanics of the PIC-RGD network. The biocompatibility of our model was assessed through phenotyping cultured human foreskin fibroblasts (HFF) and murine C2C12 myoblasts. Immunofluorescence analysis revealed that PIC-PASA hydrogels inhibit the fibrotic behavior of HFFs while promoting myogenesis in C2C12 cells without electrical stimulation. The composite PIC-PASA hydrogel can actively change the cell fate of different cell types, providing an attractive tool to improve skin and muscle repair.
摘要:
疾病建模和药物筛选应用迫切需要紧密类似于天然组织的可靠体外模型。最近,导电生物材料在体外模型的开发中受到越来越多的关注,因为它们允许外源电信号引导细胞朝向所需的细胞反应。有趣的是,他们已经证明,即使没有外部电刺激,它们也能促进细胞增殖和粘附。本文介绍了一种导电,基于肽修饰的聚异氰化物(PIC-RGD)和相对导电的聚(苯胺-共-N-(4-磺基苯基)苯胺)(PASA)的混合物的全合成水凝胶及其作为体外基质的适用性。我们证明,掺入PASA可增强PIC-RGD水凝胶的电活性性质,而不会显着改变PIC-RGD网络的纤维结构和非线性力学。通过对培养的人包皮成纤维细胞(HFF)和鼠C2C12成肌细胞进行表型分析来评估我们模型的生物相容性。免疫荧光分析显示,PIC-PASA水凝胶抑制HFF的纤维化行为,同时在无电刺激的情况下促进C2C12细胞的肌生成。PIC-PASA复合水凝胶能主动改变不同细胞类型的细胞命运,提供了一个有吸引力的工具,以改善皮肤和肌肉修复。