oa Designer scaffolds for tissue engineering heart valves

Collagen fibers are essential components of tissues and an important protein in the extracellular matrix, which maintains the structural and mechanical integrity of tissues while providing key signals to regulate cell functions. Although animal-based collagens can be used as biomaterial for tissue engineering heart valves, they cause infections and lack flexibility. These limitations have stimulated the exploration of collagen mimetic peptides (CMPs) through a bottom-up approach using computational modeling followed by experiments. Here, a 3D-structure of 3-helices of CMP was used to model the new CMPs to identify its structural stability and hotspots. These data assist in introducing charged residues by mutations to cross-link 3-helices and to add binding motif (GFOGER) for integrin in the CMP structures. The helical stability and self-association of the mutated CMPs have been validated using molecular dynamics (MD) simulations, surface electrostatic calculation followed by biochemical experiments using HPLC and mass spectrometry. The modelling analyses indicated that the CMPs show the desired structural properties for self-assembly and high affinity towards integrin binding. The introduction of the charged residues increased the possibilities for helical cross-link (gelation). The results suggest that altering the positions and length of hydrophobic repeats (GPO) of CMPs could improve thermal stability (Figure). The structural properties of the modelled CMPs were reproduced in experimental conditions. Our study provides potential peptide candidates that promise to show some inherent structural properties of native collagen in silico and in vitro. These properties are required to produce functional scaffolds for tissue engineering heart valves.