Electroactive extracellular Matrix/Polypyrrole composite films and their microenvironmental effects on osteogenic differentiation of BMSCs

Abstract

Bone marrow mesenchymal stem cells (BMSCs) could be regulated through their microenvironment, which includes biological cues of extracellular matrix (ECM) and other endogenous physical cues. In this work, cell-derived ECM was used as a framework to prepare extracellular matrix/polypyrrole composite films by chemical polymerization of polypyrrole (Ppy). The composite film retained the microstructure of ECM, while the microscopic surface exhibited dual-exposure of ECM and Ppy. The content of Ppy had a decisive influence on the protein exposure area and electrochemical performance to generate different biological or electrical microenvironment. It was worth noting that the ECM/Ppy composite films with appropriate Ppy content had unique biological microenvironments that could promote the osteogenic differentiation of BMSCs. In addition, the electrochemical performance of ECM/Ppy composite films had been significantly improved compared with ECM, which meant that they were electroactive. When BMSCs were simultaneously affected by biological microenvironment and electrical microenvironment, this new composite electroactive film showed the best ability to promote osteogenic differentiation. Correspondingly, the microenvironment provided by ECM/Ppy composite films significantly up-regulated the expression of genes related to osteogenic differentiation of ALP, Col-I, and RunX-2. Furthermore, the electrical microenvironment had been shown to regulate the osteogenic differentiation of BMSCs through the influence on the intracellular calcium ion (Ca2+) concentration and related signal pathways. This new composite electroactive biomaterial has unique biochemical properties and good electrochemical properties to construct biological and electrical microenvironment, having great potential in research and application of bone tissue regeneration and regenerative medicine.