Tissue origin matters: Maintenance of tenogenic phenotype on the tendon and not skin collagen‐derived devices

Abstract

Abstract Recent data suggest that collagen retains the memory of the tissue that it derives from. With this in mind, collagen (from bovine skin and tendon) sponges were fabricated with different crosslinking densities, and their physicochemical and biological properties were assessed. As the crosslinking density was increased, the resistance to collagenase digestion, denaturation temperature, compressive stress, and compressive modulus was significantly increased and the free amine content, % swelling, and human dermal fibroblast cytocompatibility were significantly reduced. The tendon‐collagen‐derived scaffolds exhibited significantly higher compressive stress and compressive modulus values and induced significantly higher human tenocyte DNA concentration and metabolic activity than the skin‐collagen‐derived scaffolds. In human tenocyte cultures on day 14, the 1 mM 4‐arm polyethylene‐glycol succinimidyl glutarate tendon‐collagen‐derived collagen sponges induced significantly higher collagen type III synthesis (as expected at early stages of physiological tendon healing) and downregulated actin alpha 2 (associated with myofibroblast differentiation) and the skin‐collagen‐derived collagen sponges induced significantly higher collagen type IV synthesis (found primarily at the dermal‐epidermal junction) and upregulated prolyl 4‐hydroxylase subunit alpha‐1 (associated with collagen biosynthesis and constitutes a target for antifibrotic compounds). Our data indicate that the tissue from which collagen is extracted should be considered in the development of medical devices.

Keywords

• collagen biomaterials
• collagen crosslinking
• human tenocytes
• skin collagen
• tendon collagen