Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, 100084, China.
Department of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China.
Nat Commun. 2019 Aug 2;10(1):3491. doi: 10.1038/s41467-019-11397-1.
Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.
尽管应用广泛，但由于缺乏将结构和机械性能之间复杂相互作用解耦的方法，目前仍未对 3D 多孔支架进行系统的力学生物学研究。在这里，我们发现了冷冻保护剂对冰晶生长的调节作用，并利用这一特性实现了支架孔径和硬度的单独控制。成纤维细胞和巨噬细胞对明胶支架的结构和机械性能都很敏感，尤其是对孔径。有趣的是，较小和较软的孔中的巨噬细胞表现出促炎表型，而较大和较硬的孔则诱导抗炎表型。这种结构调节的细胞力学响应归因于孔或渗透压引起的物理限制。最后，通过植入支架在体内刺激内源性成纤维细胞和巨噬细胞产生类似于体外相应细胞的力学响应，表明支架的物理性质可用于调节组织再生。
