Rapid fabrication of tendon-like collagen gel via simultaneous fibre alignment and intermolecular cross-linking under mechanical loading

Artificial tissue replacement is a promising strategy for better healing outcomes for tendon and ligament injuries, due to the very limited self-regeneration capacity of these tissues in mammals, including humans. Because clinically available synthetic and biological scaffolds for tendon repair have performed more poorly than autografts, both biological and mechanical compatibility need to be improved. Here we propose a rapid fabrication method for tendon-like structure from collagen hydrogel, simultaneously achieving collagen fibre alignment and intermolecular cross-linking. Collagen gel, 24 h after polymerization, was subjected to mechanical loading in the presence of the chemical cross-linker, genipin, for 24 or 48 h. Mechanical loading during gel incubation oriented collagen fibres in the loading direction and made chemical cross-linking highly effective in a loading magnitude-dependent manner. Gel incubated with 4 g loading in the presence of genipin for 48 h possessed tensile strength of 4 MPa and tangent modulus of 60 MPa, respectively, which could fulfill the minimum biomechanical requirement for artificial tendon. Although mechanical properties of gels fabricated using the present method can be improved by using a larger amount of collagen in the starting material and through optimisation of mechanical loading and cross-linking, the method is a simple and effective for producing highly aligned collagen fibrils with excellent mechanical properties.