Programming peptide-collagen hybrid hydrogels for tissue engineering applications

Abstract

Self-assembled short peptide hydrogels based on natural proteins have been designed to mimic natural environment of extracellular matrix (ECM) in tissue. Yet this class of hydrogels solely lacks the ability to represent the entire complexity of the ECM. To address this problem, requires novel design of synthetic materials incorporating natural biopolymers. In this work, library of peptides based on protein motifs were designed that form self-assembled hydrogel. Animal source or human source biopolymers were then mixed with these peptides to fabricate dual-functional hybrid hydrogels. The incorporation of biopolymers at a concentration much lower than the peptide concentration, drastically enhanced the mechanical property of these hybrid systems. Both animal and human biopolymers are commercially available at high cost, however, incorporating minimum concentrations of both into this novel hybrid hydrogel will reduce the need for the biopolymer in a cost-effective manner. Additionally, these hybrid hydrogel systems are readily tuned by designing or re-arranging the target peptides sequences to fulfil the required applications of these hydrogels. Another peptide carrying cell-adhesion epitope, was designed based on a key binding motif for skin cells. The peptide self-assembled into self-supporting hydrogel. While biological compatibility of this gelator with skin cells was suboptimal over a long period of time, on the other hand, in 2D cultures of human Mesenchymal Stem Cells (hMSCs) no adverse reactions were noted and the hMSCs were shown to spread over a 7 days period on top of the hydrogel formed. Remarkably, exposure of this peptide to light triggered dynamic assembly. This photo-induced modulation of peptide assembly could be harvested for future therapeutic applications.