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.

治疗纤维化疾病的有效疗法很少，例如皮肤疤痕、肝硬化和肺纤维化，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-基质相互作用、细胞-细胞接触、流体流动和其他物理刺激的机械力可能在纤维化的发生和传播中起着核心作用。在这篇综述中，我们强调了各种物理力来源驱动纤维化疾病过程的机械转导机制，重点是可能在治疗上靶向预防和逆转纤维化的中枢途径。然后，我们讨论了纤维化中机械转导的工程模型，以及用于限制纤维化和促进各种器官再生愈合表型的基于分子和生物材料的治疗方法。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受益匪浅。