Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.

中文翻译：

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工程外泌体作为糖尿病足溃疡的前瞻性疗法


糖尿病足溃疡（DFU）具有高复发率、高截肢率和高死亡率的特点，对糖尿病治疗提出了重大挑战。复杂的病理学涉及葡萄糖稳态失调，导致全身和局部微环境并发症，包括周围神经病变、微血管病变和大血管病变、反复感染、持续炎症和上皮化失调。人们正在积极寻求加速 DFU 愈合的新方法，重点是利用外泌体。外泌体是介导细胞通讯的天然纳米囊泡，含有多种功能分子货物，包括 DNA、mRNA、microRNA (miRNA)、lncRNA、蛋白质、脂质和代谢物。虽然一些外泌体在调节细胞功能和促进溃疡愈合方面显示出希望，但其功效受到产量低、杂质、负载量低和靶向性不足的限制。改造外泌体以增强其治疗活性是治疗 DFU 的一种可能更有效的方法。这可以促进溃疡发展后神经、血管和软组织的集中修复和再生。本综述概述了 DFU 发病机制、外泌体工程策略以及工程外泌体在解决与 DFU 相关的关键病理变化方面的靶向治疗应用。