Mascharak Shamik, Guo Jason L, Griffin Michelle, Berry Charlotte E, Wan Derrick C, Longaker Michael T
Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nat Rev Bioeng. 2024 Apr;2(4):305-323. doi: 10.1038/s44222-023-00144-3. Epub 2024 Jan 18.
Few efficacious therapies exist for the treatment of fibrotic diseases, such as skin scarring, liver cirrhosis and pulmonary fibrosis, which is related to our limited understanding of the fundamental causes and mechanisms of fibrosis. Mechanical forces from cell-matrix interactions, cell-cell contact, fluid flow and other physical stimuli may play a central role in the initiation and propagation of fibrosis. In this Review, we highlight the mechanotransduction mechanisms by which various sources of physical force drive fibrotic disease processes, with an emphasis on central pathways that may be therapeutically targeted to prevent and reverse fibrosis. We then discuss engineered models of mechanotransduction in fibrosis, as well as molecular and biomaterials-based therapeutic approaches for limiting fibrosis and promoting regenerative healing phenotypes in various organs. Finally, we discuss challenges within fibrosis research that remain to be addressed and that may greatly benefit from next-generation bioengineered model systems.
对于诸如皮肤瘢痕形成、肝硬化和肺纤维化等纤维化疾病，有效的治疗方法很少，这与我们对纤维化的根本原因和机制的了解有限有关。来自细胞与基质相互作用、细胞间接触、流体流动及其他物理刺激的机械力可能在纤维化的起始和进展中起核心作用。在本综述中，我们重点介绍了各种物理力驱动纤维化疾病进程的机械转导机制，尤其强调了可能成为治疗靶点以预防和逆转纤维化的核心途径。然后，我们讨论了纤维化中机械转导的工程模型，以及基于分子和生物材料的治疗方法，这些方法用于限制纤维化并促进各器官的再生愈合表型。最后，我们讨论了纤维化研究中仍有待解决的挑战，这些挑战可能会从下一代生物工程模型系统中大大受益。
