Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

中文翻译：

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皮肤伤口修复和再生中的生物工程 MSC 衍生外泌体

压力性溃疡、糖尿病性溃疡和血管性溃疡等难治性皮肤缺损对临床医生和研究人员提出了多方面的挑战。伤口愈合的治疗策略成本高且疗效有限。为了减轻患者的经济和心理负担，需要更有效的治疗方法来解决慢性伤口。MSC 衍生的外泌体（MSC-外泌体）是 MSC 旁分泌作用的主要生物活性细胞外囊泡，已被提议作为一种新的潜在无细胞方法用于伤口愈合和皮肤再生。MSC-外泌体的好处包括它们促进血管生成和细胞增殖、增加胶原蛋白生成、调节炎症以及最终提高组织再生能力的能力。然而，MSC-外泌体的靶向性差和易于从伤口去除是其在临床治疗中使用的主要障碍。因此，已经引入生物工程技术的概念来修饰外泌体，从而能够实现更高浓度和构建具有更高稳定性和特定治疗能力的颗粒。使用生物材料装载 MSC 外泌体可能是一种有前途的策略，可以集中剂量、产生所需的治疗效果并保持缓释效果。MSC-外泌体在伤口愈合中的有益作用已被广泛接受；然而，生物工程修饰的 MSC 外泌体的潜力仍不清楚。在这篇综述中，我们试图总结修饰的 MSC-外泌体在伤口愈合和皮肤再生中的治疗应用。