Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
PLoS One. 2011;6(7):e22139. doi: 10.1371/journal.pone.0022139. Epub 2011 Jul 11.
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 masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing.
皮肤瘢痕是一个未满足的临床重大问题，严重影响患者的生活质量。伤口愈合是一个复杂的过程，涉及多个高度协调的途径，使皮肤保持封闭，但组织成分（即胶原和蛋白聚糖）的排列和组成异常，随后这些组织成分会随时间重塑。为了改善愈合并减少或消除瘢痕，更快地恢复健康的组织成分和排列为开发新疗法提供了独特的方法。已经开发出一种合成的胶原结合肽聚糖，可抑制基质金属蛋白酶-1 和 13（MMP-1 和 MMP-13）介导的胶原降解。我们在大鼠切口模型中研究了这种合成的肽聚糖，在手术时于伤口闭合前用透明质酸（HA）载体单次给药。组织学和视觉分析表明，肽聚糖处理在第 21 天时可显著减少瘢痕组织。与未处理和 HA 对照组相比，处理过的伤口的胶原结构得到改善，表现为拉伸强度增加，胶原纤维直径的透射电子显微镜（TEM）分析增加。肽聚糖的作用机制包括掩盖现有胶原和抑制 MMP 介导的胶原降解，同时调节胶原组织。肽聚糖可以低成本合成，并具有独特的设计控制，加上在减少瘢痕方面的临床前疗效，值得进一步研究用于皮肤伤口愈合。
