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糖尿病足溃疡的临床前研究:从发病机制到体内/体外模型及临床治疗转化。

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.

机构信息

Department of Peripheral Vascular Surgery, Institute of surgery of traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Endocrinology department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Int Wound J. 2023 Dec;20(10):4394-4409. doi: 10.1111/iwj.14311. Epub 2023 Jul 12.

DOI:10.1111/iwj.14311
PMID:37438679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10681512/
Abstract

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.

摘要

糖尿病足溃疡(DFU)是糖尿病(DM)常见的难治性慢性并发症,其患病率高达 25%,超过 17%的患者存在截肢甚至死亡的风险。血管危险因素,包括血管狭窄或闭塞、血脂异常、神经感觉和运动功能受损以及创伤引起的皮肤感染,都会增加糖尿病患者发生 DFU 的风险。因此,糖尿病足并不是单一的发病机制。临床前研究为 DFU 的发病机制确定和疗效评估做出了巨大贡献。目前,许多治疗工具正在使用 DFU 动物模型进行研究,以期实现有效的临床转化。然而,完全模拟 DFU 发病机制的临床前动物模型仍未得到探索。因此,在这篇综述中,详细讨论了三种主要病理机制(神经病变、血管病变和 DFU 感染)的 DFU 动物模型的制备方法和评价标准。并讨论了各种 DFU 动物模型在模拟临床体征方面的优缺点。此外,还介绍了 DFU 的体外模型现状以及一些已转化为临床治疗方案的临床前研究,如医用敷料、生长因子治疗、3D 生物打印和预血管化、中药治疗。然而,由于 DFU 的发病机制复杂,DFU 模型的临床转化仍然面临许多挑战。我们需要进一步优化现有的 DFU 临床前研究,为未来研究 DFU 的病理生理学和临床治疗提供有效的动物平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/10681512/85a74468b41c/IWJ-20-4394-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/10681512/e34c8e6daca6/IWJ-20-4394-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/10681512/85a74468b41c/IWJ-20-4394-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/10681512/e34c8e6daca6/IWJ-20-4394-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/201c/10681512/85a74468b41c/IWJ-20-4394-g007.jpg

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