Chronic wounds are an unmet clinical need affecting millions of patients globally, and current standards of care fail to consistently promote complete wound closure and prevent recurrence. Disruptions in growth factor signaling, a hallmark of chronic wounds, have led researchers to pursue growth factor therapies as potential supplements to standards of care. Initial studies delivering growth factors in protein form showed promise, with a few formulations reaching clinical trials and one obtaining clinical approval. However, protein-form growth factors are limited by instability and off-target effects. Gene therapy offers an alternative approach to deliver growth factors to the chronic wound environment, but safety concerns surrounding gene therapy as well as efficacy challenges in the gene delivery process have prevented clinical translation. Current growth factor delivery and gene therapy approaches have primarily used single growth factor formulations, but recent efforts have aimed to develop multi-growth factor approaches that are better suited to address growth factor insufficiencies in the chronic wound environment, and these strategies have demonstrated improved efficacy in preclinical studies. This review provides an overview of chronic wound healing, emphasizing the need and potential for growth factor therapies. It includes a summary of current standards of care, recent advances in growth factor, cell-based, and gene therapy approaches, and future perspectives for multi-growth factor therapeutics.

中文翻译：

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用于治疗慢性伤口的生长因子和生长因子基因疗法


慢性伤口是一个未得到满足的临床需求，影响着全球数百万患者，而当前的护理标准无法持续促进伤口完全闭合并防止复发。生长因子信号传导的破坏是慢性伤口的标志，促使研究人员寻求生长因子疗法作为护理标准的潜在补充。以蛋白质形式提供生长因子的初步研究显示出希望，一些配方进入了临床试验，其中一种获得了临床批准。然而，蛋白质形式的生长因子受到不稳定和脱靶效应的限制。基因治疗提供了另一种将生长因子传递到慢性伤口环境的方法，但围绕基因治疗的安全性问题以及基因传递过程中的功效挑战阻碍了临床转化。目前的生长因子递送和基因治疗方法主要使用单一生长因子制剂，但最近的努力旨在开发更适合解决慢性伤口环境中生长因子不足的多生长因子方法，并且这些策略已证明疗效提高在临床前研究中。这篇综述概述了慢性伤口愈合，强调了生长因子疗法的必要性和潜力。它总结了当前的护理标准、生长因子、细胞和基因治疗方法的最新进展，以及多生长因子治疗的未来前景。