Biological wound matrices with native dermis-like collagen efficiently modulate protease activity

OBJECTIVE: When the delicate balance between catabolic and anabolic processes is disturbed for any reason, the healing process can stall, resulting in chronic wounds. In chronic wound pathophysiology, proteolytic imbalance is implicated due to elevated protease levels mediating tissue damage. Hence, it is important to design appropriate wound treatments able to control and modulate protease activity directly at the host/biomaterial interface. Here, we investigate collagen-based wound dressings with the focus on their potential to adsorb and inactivate tissue proteases. METHOD: We examined the effect of six collagen-based dressings on their ability to adsorb and inactivate different granulocyte proteases, plasmin, human neutrophil elastase (HLE), and matrix metalloproteases (MMP)-1, -2, -8, and -9, by an integrated approach including immunoelectron microscopy. RESULTS: We observed a reduction of the proteolytic activities of plasmin, HLE, and MMP-1, -2, -8, and -9, both on the biomaterial surface and in human chronic wound fluid. The most pronounced effect was observed in collagen-based dressings, with the highest content of native collagen networks resembling dermis structures. CONCLUSION: Our data suggest that this treatment strategy might be beneficial for the chronic wound environment, with the potential to promote improved wound healing.