Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Department of Anesthesiology and Critical Care Medicine and Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Nat Cardiovasc Res. 2023 Aug;2(8):718-732. doi: 10.1038/s44161-023-00311-0. Epub 2023 Aug 10.
Mechanical stimuli from the extracellular matrix (ECM) modulate vascular differentiation, morphogenesis and dysfunction of the vasculature. With innovation in measurements, we can better characterize vascular microenvironment mechanics in health and disease. Recent advances in material sciences and stem cell biology enable us to accurately recapitulate the complex and dynamic ECM mechanical microenvironment for in vitro studies. These biomimetic approaches help us understand the signaling pathways in disease pathologies, identify therapeutic targets, build tissue replacement and activate tissue regeneration. This Review analyzes how ECM mechanics regulate vascular homeostasis and dysfunction. We highlight approaches to examine ECM mechanics at tissue and cellular levels, focusing on how mechanical interactions between cells and the ECM regulate vascular phenotype, especially under certain pathological conditions. Finally, we explore the development of biomaterials to emulate, measure and alter the physical microenvironment of pathological ECM to understand cell-ECM mechanical interactions toward the development of therapeutics.
细胞外基质(ECM)产生的机械刺激调节血管分化、形态发生和血管功能障碍。通过测量方法的创新,我们可以更好地描述健康和疾病状态下血管微环境的力学特性。材料科学和干细胞生物学的最新进展使我们能够准确地再现体外研究中复杂和动态的 ECM 力学微环境。这些仿生方法有助于我们理解疾病病理中的信号通路,确定治疗靶点,构建组织替代物并激活组织再生。本文综述了 ECM 力学如何调节血管稳态和功能障碍。我们强调了在组织和细胞水平上检测 ECM 力学的方法,重点讨论了细胞与 ECM 之间的机械相互作用如何调节血管表型,尤其是在某些病理条件下。最后,我们探讨了生物材料的发展,以模拟、测量和改变病理性 ECM 的物理微环境,从而了解细胞-ECM 力学相互作用,以开发治疗方法。