3B's Research Group, I3Bs-Research Institute on Biomaterials Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimarães, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Guimarães, Portugal.
Tissue Eng Part B Rev. 2022 Jun;28(3):665-676. doi: 10.1089/ten.TEB.2021.0030. Epub 2021 Oct 18.
Wound re-epithelialization is a dynamic process that comprises the formation of new epithelium through an active signaling network between several growth factors (GFs) and various cell types. The main players are keratinocytes (KCs) that migrate from the wound edges over the wound bed to restore the epidermal barrier. One of the most important molecules involved in the re-epithelialization process is keratinocyte growth factor (KGF), a central player on promoting both migration and proliferation of KCs. Stromal cells, such as dermal fibroblasts, are the main producers of this factor, acting on KCs through paracrine signaling. Multiple therapeutic strategies to deliver KGF have been proposed to boost wound healing by targeting re-epithelialization. Different approaches have been explored to attain that purpose, such as topical application of this factor, controlled release of KGF from different biomaterials (hydrogels, nanoparticles, and membranes), and also gene delivery techniques. Among these strategies, KGF release via biomaterials- and genetic-based strategies shows great effectiveness in maintaining sustained KGF levels at the wound site, which is reflected in an efficient wound closure. Under this scope, this review aims not only to elucidate the potential of KGF in wound re-epithelialization but also to describe the underlying mechanism of action and further explore the therapeutic approaches using this GF. Impact statement Upon skin injury, wound re-epithelialization is one of the major milestones of the healing process. This is especially difficult to achieve on hard-to-heal wounds that are often open for long periods, as the dysregulation of the growth factors involved in this response contributes to an impaired proliferation and migration of keratinocytes. Keratinocyte growth factor (KGF) plays a central role in this problematic, as it is a potent factor that in the normal healing scenario promotes direct proliferation and migration of epidermal cells, consequently impacting re-epithelialization. Under this context, in the first part of this review, the process of wound healing and the mechanism of action of KGF are described. In the second part, various KGF delivery approaches aiming at skin re-epithelialization are reported and actively discussed. In this sense, it is herein highlighted the role of KGF in wound re-epithelialization and provided a critical overview of potential therapeutic strategies exploited so far.
创伤再上皮化是一个动态的过程，它包括通过几种生长因子（GFs）和各种细胞类型之间的活跃信号网络形成新的上皮。主要参与者是角质形成细胞（KCs），它们从伤口边缘迁移到伤口床上，以恢复表皮屏障。参与再上皮化过程的最重要分子之一是角质形成细胞生长因子（KGF），它是促进角质形成细胞迁移和增殖的核心分子。间质细胞，如真皮成纤维细胞，是这种因子的主要产生者，通过旁分泌信号作用于角质形成细胞。已经提出了多种递送 KGF 的治疗策略，通过靶向再上皮化来促进伤口愈合。为了达到这个目的，已经探索了不同的方法，例如局部应用这种因子、从不同的生物材料（水凝胶、纳米颗粒和膜）中控制释放 KGF，以及基因传递技术。在这些策略中，通过生物材料和遗传为基础的策略释放 KGF 在维持伤口部位持续的 KGF 水平方面显示出极大的效果，这反映在有效的伤口闭合上。在这个范围内，本综述不仅旨在阐明 KGF 在创伤再上皮化中的潜力，还描述其作用机制，并进一步探索使用这种 GF 的治疗方法。
影响说明
在皮肤损伤后，创伤再上皮化是愈合过程中的主要里程碑之一。在难以愈合的伤口中，这尤其困难，因为涉及到这种反应的生长因子的失调会导致角朊细胞增殖和迁移受损。角质形成细胞生长因子（KGF）在这个问题中起着核心作用，因为它是一种有效的因子，在正常的愈合情况下促进表皮细胞的直接增殖和迁移，从而影响再上皮化。在这种情况下，在本综述的第一部分中，描述了伤口愈合的过程和 KGF 的作用机制。在第二部分中，报告了各种旨在实现皮肤再上皮化的 KGF 传递方法，并进行了积极讨论。在这方面，本文强调了 KGF 在创伤再上皮化中的作用，并对迄今为止所利用的潜在治疗策略进行了批判性综述。
