collagen-binding peptidoglycans inhibit mmp mediated collagen degradation and reduce dermal scarringcollagen-binding肽聚糖抑制mmp介导胶原降解,减少皮肤疤痕.pdfVIP

Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring 1. 1. 2 1,2 1 Kate Stuart , John Paderi , Paul W. Snyder , Lynetta Freeman , Alyssa Panitch * 1 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America, 2 School of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America Abstract Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13) mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA) vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM) analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan’s mechanism of action includes mask