Department of Pathology and Medical Biology and University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Plastic Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Tissue Eng Part B Rev. 2022 Oct;28(5):1093-1108. doi: 10.1089/ten.TEB.2021.0120. Epub 2021 Dec 30.
Chronic, non-healing, dermal wounds form a worldwide medical problem with limited and inadequate treatment options and high societal burden and costs. With the advent of regenerative therapies exploiting extracellular matrix (ECM) components, its efficacy to augment wound healing is to be explored. This systematic review was performed to assess and compare the current therapeutic efficacy of ECM hydrogels on dermal wound healing. The electronic databases of Embase, Medline Ovid, and Cochrane Central were searched for and clinical studies on the therapeutic effect of ECM-composed hydrogels on dermal wound healing (April 13, 2021). Two reviewers selected studies independently. Studies were assessed based on ECM content, ECM hydrogel composition, additives, and wound healing outcomes, such as wound size, angiogenesis, and complications. Of the 2102 publications, 9 rodent-based studies were included while clinical studies were not published at the time of the search. Procedures to decellularize tissue or cultured cells and subsequently generate hydrogels were highly variable and in demand of standardization. ECM hydrogels with or without additives reduced wound size and also seem to enhance angiogenesis. Serious complications were not reported. To date, preclinical studies preclude to draw firm conclusions on the efficacy and working mechanism of ECM-derived hydrogels on dermal wound healing. The use of ECM hydrogels can be considered safe. Standardization of decellularization protocols and implementation of quality and cytotoxicity controls will enable obtaining a generic and comparable ECM product. Impact statement Extracellular matrix (ECM)-based hydrogels are biocompatible and harbor growth factors that can instruct tissue healing. Their application is a novelty in (pre)clinical wound healing treatment. This systematic review provides an overview of the current evidence for ECM hydrogels in enhancing wound healing and an extensive overview of the decellularization procedures used. Lastly, challenges and future directions to standardize decellularization procedures and implement quality controls are proposed.
慢性、非愈合性皮肤伤口是一个全球性的医学问题，治疗选择有限且效果不佳，社会负担和成本高。随着利用细胞外基质（ECM）成分的再生疗法的出现，探索其增强伤口愈合的效果是必要的。本系统评价旨在评估和比较 ECM 水凝胶在皮肤伤口愈合中的当前治疗效果。检索了 Embase、Medline Ovid 和 Cochrane Central 电子数据库，以获取关于 ECM 组成的水凝胶对皮肤伤口愈合治疗效果的临床研究（2021 年 4 月 13 日）。两名评审员独立选择研究。研究根据 ECM 含量、ECM 水凝胶组成、添加剂和伤口愈合结果（如伤口大小、血管生成和并发症）进行评估。在 2102 篇出版物中，纳入了 9 项基于啮齿动物的研究，而当时没有发表临床研究。脱细胞组织或培养细胞并随后生成水凝胶的程序差异很大，需要标准化。有或没有添加剂的 ECM 水凝胶可减少伤口大小，并且似乎还能增强血管生成。没有报告严重并发症。迄今为止，临床前研究不能得出关于 ECM 衍生水凝胶在皮肤伤口愈合中的疗效和作用机制的明确结论。ECM 水凝胶的使用可以被认为是安全的。脱细胞化方案的标准化以及质量和细胞毒性控制的实施将使获得通用且可比的 ECM 产品成为可能。
