Designing Short Cardin-Motif Peptide and Biopolymer-Based Multicomponent Hydrogels for Developing Advanced Composite Scaffolds for Improving Cellular Behavior.

Multicomponent self-assembly represents a cutting-edge strategy in peptide nanotechnology, enabling the creation of nanomaterials with enhanced physical and biological characteristics. This approach draws inspiration from the highly complex nature of the native extracellular matrix (ECM) constituting multicomponent biomolecular entities. In recent years, the combination of bioactive peptide with polymer has gained significant attention for the fabrication of novel biomaterials due to their inherent specificity, tunable physiochemical properties, biocompatibility, and biodegradability. This advanced strategy can address the limitation of the lower mechanical strength of the individual peptide hydrogel by incorporating the biopolymer, resulting in the formation of a composite scaffold. In this direction, this advanced strategy is explored using noncovalent interactions between cellulose nano-fiber (CNF) and cationic Cardin-motif peptide to develop advanced composite scaffolds. The bioactive cationic peptide otherwise failed to form hydrogel at physiological conditions. Interestingly, the differential mixing ratio of CNF and peptide modulated the surface charge, functionality, and mechanical properties of the composite scaffolds, resulting in diverse cellular responses. 10:1 (w/w) ratio of CNF and peptide-based composite scaffold demonstrates improved cellular survival and proliferation in 2D culture conditions. Notably, in 3D cultures, cell proliferation on the 10:1 matrix is comparable to Matrigel, highlighting its potential for advanced tissue engineering applications.