Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500HB Nijmegen, The Netherlands.
Department of Oral and Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus Medical Center, P.O. Box 2060, 3000CB Rotterdam, The Netherlands.
Adv Drug Deliv Rev. 2019 Jun;146:60-76. doi: 10.1016/j.addr.2018.08.002. Epub 2018 Aug 11.
The healing of skeletal muscle injuries after major trauma or surgical reconstruction is often complicated by the development of fibrosis leading to impaired function. Research in the field of muscle regeneration is mainly focused on the restoration of muscle mass while far less attention is paid to the prevention of fibrosis. In this review, we take as an example the reconstruction of the muscles in the soft palate of cleft palate patients. After surgical closure of the soft palate, muscle function during speech is often impaired by a shortage of muscle tissue as well as the development of fibrosis. We will give a short overview of the most common approaches to generate muscle mass and then focus on strategies to prevent fibrosis. These include anti-fibrotic strategies that have been developed for muscle and other organs by the delivery of small molecules, decorin and miRNAs. Anti-fibrotic compounds should be delivered in aligned constructs in order to obtain the organized architecture of muscle tissue. The available techniques for the preparation of aligned muscle constructs will be discussed. The combination of approaches to generate muscle mass with anti-fibrotic components in an aligned muscle construct may greatly improve the functional outcome of regenerative therapies for muscle injuries.
严重创伤或外科重建后骨骼肌肉损伤的愈合常常因纤维化的发展而变得复杂,导致功能受损。肌肉再生领域的研究主要集中在恢复肌肉质量上,而对纤维化的预防关注较少。在这篇综述中,我们以腭裂患者软腭肌肉的重建为例。软腭手术后,由于肌肉组织短缺和纤维化的发展,肌肉在言语过程中的功能常常受到影响。我们将简要概述最常见的产生肌肉质量的方法,然后重点介绍预防纤维化的策略。这些策略包括通过小分子、核心蛋白聚糖和 miRNA 的递送来治疗肌肉和其他器官的抗纤维化策略。为了获得肌肉组织的有序结构,抗纤维化化合物应该在排列的结构中递送到。将讨论用于制备排列的肌肉构建体的可用技术。在排列的肌肉构建体中,将产生肌肉质量的方法与抗纤维化成分相结合,可能会极大地改善肌肉损伤再生疗法的功能结果。