Northwestern University Feinberg School of Medicine, Department of Surgery, USA.
Northwestern University Feinberg School of Medicine, Department of Surgery, USA; First Affiliated Hospital of Guangzhou Medical University, Department of Plastic and Cosmetic Surgery, China.
Exp Cell Res. 2021 Mar 15;400(2):112512. doi: 10.1016/j.yexcr.2021.112512. Epub 2021 Feb 2.
Since chronic, non-healing wounds represent an increasing source of economic and temporal burden for patients who suffer from them and healthcare professionals that treat them, therapeutic modalities that promote closure of delayed and non-healing wounds are of utmost importance. Recent clinical results of allografts derived from amnion and chorion placental layers encourage further investigation of the mechanisms underlying clinical efficacy of these products for treatment of wounds. Here, we utilized a diabetic murine splinted excisional wound model to investigate the effects of a dehydrated human amnion/chorion-derived allograft (dHACA) on delayed wound healing, as well as the effects of dehydrated allograft derived solely from amnion tissue of the same donor. We examined wound healing by histological endpoint analysis, and we assessed other parameters relevant to functional wound healing in the wound bed including angiogenesis, macrophage phenotypes, proliferative activity, and gene expression. Herein we demonstrate that application of dHACA to a murine diabetic model of delayed wound progression results in better macroscale wound resolution outcomes, including rate of closure, compared to unaided wound progression, while dehydrated human amnion allograft (dHAA) fails to improve outcomes. Improved gross wound resolution observed with dHACA was accompanied by increased granulation tissue formation, proliferation and vascular ingrowth observed in the wound bed, early macrophage polarization towards anti-inflammatory phenotypes, and downregulation of pro-fibrotic gene expression. Overall, our data suggest that improvements in the rates of delayed wound closure observed from combined amnion/chorion allografts are associated with modulation of critical cellular and tissue processes commonly found to be dysregulated in delayed healing wounds, including proliferation, vascularization, inflammation, and re-epithelialization.
由于慢性、难以愈合的伤口给患者和治疗这些伤口的医疗保健专业人员带来了越来越大的经济和时间负担，因此，促进延迟和难以愈合伤口闭合的治疗方法至关重要。最近从羊膜和胎盘绒毛膜层衍生的同种异体移植物的临床结果鼓励进一步研究这些产品治疗伤口的临床疗效的机制。在这里，我们利用糖尿病小鼠夹板切除伤口模型来研究脱水人羊膜/绒毛膜衍生同种异体移植物（dHACA）对延迟伤口愈合的影响，以及仅来自同一供体羊膜组织的脱水同种异体移植物的影响。我们通过组织学终点分析检查伤口愈合，并评估与伤口床中功能性伤口愈合相关的其他参数，包括血管生成、巨噬细胞表型、增殖活性和基因表达。在这里，我们证明将 dHACA 应用于糖尿病小鼠延迟伤口进展模型可导致更好的宏观伤口愈合结果，包括闭合率，与未经处理的伤口进展相比，而脱水人羊膜同种异体移植物（dHAA）不能改善结果。与 dHACA 观察到的改善宏观伤口愈合相关的是伤口床中观察到的肉芽组织形成、增殖和血管生成增加，早期巨噬细胞向抗炎表型极化，以及促纤维化基因表达下调。总体而言，我们的数据表明，从羊膜/绒毛膜联合同种异体移植物观察到的延迟伤口闭合率的提高与调节在延迟愈合伤口中通常失调的关键细胞和组织过程有关，包括增殖、血管生成、炎症和再上皮化。
