Knecht Raphael S, Bucher Christian H, Van Linthout Sophie, Tschöpe Carsten, Schmidt-Bleek Katharina, Duda Georg N
Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Front Bioeng Biotechnol. 2021 Feb 12;9:614508. doi: 10.3389/fbioe.2021.614508. eCollection 2021.
A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin.
局部免疫组成的错误导向或失衡通常是导致瘢痕形成或纤维化的再生失败的原因之一。成功的愈合需要炎症的启动保持平衡，并及时下调炎症反应，以重新建立生物学和力学上的稳态。虽然基于生物材料的控制局部免疫反应的方法正在成为潜在的新治疗选择，但生物物理材料特性本身在调节局部免疫微环境反应中所起的作用，迄今为止仅偶尔被考虑。细胞外基质、非造血细胞和免疫细胞之间的通讯回路似乎对机械信号特别敏感，并且似乎在局部炎症环境的启动和促进中发挥作用。在这篇综述中，我们重点关注细胞外基质与其机械触发因素之间的相互作用，以及它们如何在组织再生过程中影响免疫细胞和非造血细胞以及它们之间的相互作用。我们认识到，特别是机械敏感受体，如TRPV4和PIEZO1以及机械敏感转录因子YAP/TAZ，在各种器官环境中的再生中至关重要。这表明基于在骨骼以及肺、心脏和皮肤中发现的免疫-机械原理，改善组织再生的治疗方法有了新的机会。
