Development of Collagen-Like Peptide Hydrogel Biomaterials for Soft Tissue Repair

Abstract

Unmet needs in soft tissue repair, such as chronic wounds, scarring, corneal blindness, and heart failure, urgently require new therapies. Hydrogel soft biomaterials offer a promising solution. While traditionally classified as polymers from natural or synthetic sources, advancements in chemical synthesis now enable the synthetic production of natural biofunctional molecules like peptides and proteins. Thus, bioinspired synthetic hydrogels can be designed as reliable, cost-effective and pathogen-free alternatives for soft tissue repair.

Synthetic collagen-like peptides (CLPs) can form natural tissue structures and self-assemble into triple-helix trimers to create 3D hydrogels. In this doctoral dissertation, I developed CLP materials using supramolecular self-assembly and either spontaneous thiol-maleimide Michael addition or photoactivated radical thiol-ene reactivity. A low-volume, rapid combinatory screening approach identified ideal candidates from a library of synthetic peptides. Adjusting peptide concentration or structural properties like junction functionality and reactive group choice allows for hydrogel tuning.

Ex vivo, in vitro, and in vivo assays assessed the materials' soft tissue repair capabilities. Collagenase degradation and live/dead assays showed suitable biocompatibility and biodegradability. Peptide hydrogels sealed corneal perforations or altered corneal shape. Skin adhesion tests showed strong wound closure strength comparable to commercial adhesives. In vivo wound treatment accelerated healing while reducing epithelial thickness and increasing collagen content. In a mouse model of myocardial infarction, CLP hydrogel-treated hearts preserved function at 28 days, while saline control lost function. These results suggest that peptide-based hydrogels are a promising platform for soft tissue repair of the skin, cornea, and heart.