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

The 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 great attention owing to their biocompatibility, diverse biofunctionalities and biodegradability. Additionally, the employment of 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>i.e.</i>, laminin. In the present work, we mainly focus on the α5β1 laminin protein-derived peptide sequence, IVVSIVNGR. The gelation in this short, newly identified peptide sequence was induced through a solvent-mediated self-assembly approach. To our knowledge, this is the first report exploring the hydrogelation behavior and biological applications of this ECM-derived bioactive peptide sequence. Interestingly, by varying the concentration of the peptide, we were able to access diverse gels with differential nanofibrous morphologies, mechanical behaviors, and cellular responses. Biocompatibility and cellular proliferation studies on 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 offered a more uniform and suitable interface for cellular adhesion and interactions than 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.