Designing highly tunable laminin inspired bioactive peptide hydrogel based biomaterials for directing cellular response

Abstract

Extracellular matrix (ECM) plays a crucial role in regulating cellular interactions and cell signaling pathways through several biochemical cues. In this context, designing bioinspired ECM mimics, particularly supramolecular hydrogels derived from major ECM components, has gained utmost attention owing to their biocompatibility, diverse biofunctionalities and biodegradability. Additionally, employing non-conventional approaches to control self-assembly and access diverse properties in a single molecular domain is emerging as a powerful strategy to fabricate tunable biomaterials. Therefore, by combining these two strategies, we explored one of the crucial basal membrane proteins of the ECM, i.e., Laminin. In the present work, we are mainly focusing on the α5β1 laminin protein derived peptide sequence, IVVSIVNGR. The gelation in this short newly identified peptide sequence was induced through solvent mediated self-assembly approach. To our knowledge, this is the first time this ECM-derived bioactive peptide sequence has been used for exploring its hydrogelation behavior and biological applications. Interestingly, by varying the concentration of the peptide, we were able to access diverse gels with differential nanofibrous morphology, mechanical behavior and cellular response. The biocompatibility and cellular proliferation studies for the hydrogels were performed using both neuronal (SH-SY5Y) and fibroblast (L929) cell lines. The results demonstrated that as the peptide concentration increases, more entangled networks of nanofibers were formed that presented a more uniform and suitable interface for cellular adhesion and interactions as compared to the loosely bound, wider fibrous structures formed at lower concentration, as evident from the 2D and 3D cell culture studies. Thus, this study highlights the potential of these newly designed laminin-inspired cell-instructive scaffolds for possible futuristic applications in tissue engineering.