Extracellular matrix structure and function in diabetic wound healing

慢性无法愈合的伤口是糖尿病的一个重要并发症，导致显著的发病率、生产力损失和医疗费用。肥胖和糖尿病发病率的上升增加了糖尿病伤口的风险。尽管这些慢性伤口产生了巨大的影响，但一直缺乏有效的治疗方法。纠正或预防糖尿病损害的伤口愈合对患者的预后、医疗保健支出和公共健康具有深远的影响。 正常的伤口愈合是一个复杂的过程，涉及多种生长因子、细胞类型和复杂的信号相互作用。生长因子和趋化因子的产生、细胞募集、血管生成、细胞外基质的产生和伤口收缩的改变都被证明是导致糖尿病伤口愈合障碍的原因。 虽然这些因素被认为是糖尿病创面愈合障碍的潜在原因，但关于糖尿病真皮在损伤前或创面闭合后的生物力学特性的信息很少。生物力学性能较差的组织在结构和/或物质上被削弱，并有很高的损伤、退化、失败或其他病理风险。我们最近证明，糖尿病真皮在基线状态下具有先天较差的生物力学性能，在此之前 损伤，与非糖尿病皮肤相比，这会增加组织受损和/或失败的风险。 我们最近已经证明，用基质祖细胞(SPC)或Lenti病毒过表达SDF-1(一种参与祖细胞招募的趋化因子)治疗糖尿病创面可以纠正糖尿病创面闭合的损害。我们假设SPC或增加祖细胞募集的策略可以纠正糖尿病真皮较差的生物力学特性，并改善随后的创伤愈合。此外，SPC或SPC涉及的机制的表征 Lenti-SDF-1&945；介导的糖尿病伤口愈合损害的纠正将为修改糖尿病伤口愈合反应的策略提供进一步的洞察。

Chronic non-healing wounds represent a significant complication of diabetes, resulting in significant morbidity, lost productivity, and healthcare expenditures. The rising incidence of obesity and diabetes has increased the number of people at risk for diabetic wounds. Despite the enormous impact these chronic wounds have, effective therapies have been lacking. The correction or prevention of diabetes impaired wound healing has far reaching consequences on patient outcomes, healthcare expenditures, and public health. Normal wound healing is an intricate process involving multiple growth factors, cell types, and complex signaling interactions. Alterations in growth factor and chemokine production, cellular recruitment, angiogenesis, extracellular matrix production, and wound contraction have all been shown to contribute to the diabetic wound healing impairment. While these factors have been implicated as potential etiologies in the diabetic wound healing impairment, very little information is available about the biomechanical properties of the diabetic dermis prior to injury or following wound closure. Tissues with inferior biomechanical properties are structurally and/or materially weakened and are at high risk for injury, degeneration, failure or other pathologies. We have recently demonstrated that the diabetic dermis has inherently inferior biomechanical properties at baseline, prior to injury, which puts the tissue at increased risk for damage and/or failure when compared to non-diabetic skin. We have recently demonstrated that treatment of diabetic wounds with stromal progenitor cells (SPC) or lenti-viral overexpression of SDF-1α, a chemokine involved in progenitor recruitment, can correct the impairment in diabetic wound closure. We hypothesize that SPC, or strategies to increase progenitor recruitment, can correct the inferior biomechanical properties of the diabetic dermis and improve the subsequent wound healing following injury. In addition, characterization of the mechanisms involved in SPC or lenti-SDF-1α mediated correction of the diabetic wound healing impairment will provide further insight into strategies to modify the diabetic wound healing response.