Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

摘要: Debridement, the removal of diseased, nonviable tissue, is critical for clinicians to readily assess wound status and prepare bed advanced therapeutics or downstream active healing. Removing necrotic slough eschar through surgical mechanical methods less specific may be painful patients. Enzymatic debridement agents, such as Clostridial collagenase, selectively painlessly degrade devitalized tissue. In addition its debriding activities, highly-purified collagenase actively promotes healing, our past studies reveal that extracellular matrices digested with this enzyme yield peptides activate cellular migratory, proliferative angiogenic responses injury in vitro, promote closure vivo. Intriguingly, while Santyl® ointment, a sterile preparation containing collagenases other non-specific proteases, well-accepted enzymatic agent, role an healing entity has never been established. Based on previous pure we now ask whether mixture enzymes contained within produces matrix-derived vitro stimulate Here, identify novel collagen fragments, along collagen-associated derived from thrombospondin-1, multimerin-1, fibronectin, TGFβ-induced protein ig-h3 tenascin-C, generated collagenase-digested human dermal capillary endothelial fibroblastic matrices, which increase cell proliferation remodeling by 50–100% over controls. Using established model impaired further demonstrate dose well newly-identified chemically-synthesized ECM-derived significantly re-epithelialization 60–100% saline-treated These results not only confirm extend earlier using purified collagenase- vivo, but these Santyl®-generated, also represent exciting new opportunities creating therapies are enabled potentially go beyond debridement.