Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766-1854, USA.
Mol Cell Biochem. 2023 Aug;478(8):1835-1845. doi: 10.1007/s11010-022-04642-7. Epub 2022 Dec 27.
Treatment of nonhealing diabetic foot ulcers (DFUs) is a major clinical concern and challenge for clinicians. Despite the advancement in treatment strategies, there is no definitive treatment for complicated nonhealing DFUs. Animal models are crucial for understanding pathogenesis and investigating novel therapeutic small molecules and the rodent model is commonly used for research related to cutaneous wound healing. Sexual dimorphism and its effect on the efficacy of sex hormones in enhancing healing in cutaneous wounds using a rodent model have been discussed, however, there is a lack of data related to diabetic foot ulcers. Further, the effects of sexual dimorphism on the issues related to induction of diabetes, differential immune response, type and size of the wound, the effectiveness of topical versus systemic treatment, and molecular mechanisms involved in wound healing like hemostasis, granulation tissue formation, the response of keratinocytes and fibroblasts, inflammation, and skin anatomy are scarcely discussed. Understanding these aspects is of significance and will help in choosing the correct sex, species, and strain of rodents while investigating therapeutic small molecules for DFUs. This review critically summarized these issues and their translational aspects followed by highlighting the effect of sexual dimorphism on these important aspects.
治疗难以愈合的糖尿病足溃疡（DFU）是临床医生面临的主要问题和挑战。尽管治疗策略有所进步，但对于复杂的难以愈合的 DFU 仍没有明确的治疗方法。动物模型对于了解发病机制和研究新型治疗性小分子至关重要，啮齿动物模型常用于与皮肤伤口愈合相关的研究。性别二态性及其对激素在促进皮肤伤口愈合中的疗效的影响已在使用啮齿动物模型的研究中进行了讨论，然而，与糖尿病足溃疡相关的数据却很少。此外，性别二态性对与诱导糖尿病、免疫反应的差异、伤口的类型和大小、局部治疗与全身治疗的效果以及涉及止血、肉芽组织形成、角质形成细胞和成纤维细胞反应、炎症和皮肤解剖等伤口愈合的分子机制等问题的影响也很少被讨论。了解这些方面具有重要意义，有助于在研究用于治疗 DFU 的治疗性小分子时，选择正确的性别、物种和品系的啮齿动物。本综述批判性地总结了这些问题及其转化方面，并强调了性别二态性对这些重要方面的影响。
