Mechanical and biological properties of dual-topology fusion orthotropic bone scaffold

A dual-topology fusion orthotropic strategy was proposed in this study to design biomimetic porous scaffolds with morphology and function resembling those of natural bone. The mathematical equations of Schwarz P and Gyroid G were adjusted and combined to realize the design of anisotropic scaffolds fusing different features. The structure-property relationships of the novel anisotropic scaffolds (NG and NP) and the novel dual-topology fusion orthotropic scaffold (NG-NP) were systematically investigated using comprehensive approaches, including analytical formulations, mechanical test, finite element analysis, computational fluid dynamics, and cell experiments. The analyses covered structural characteristics (anisotropy and surface curvature), physical properties (mechanical properties and mass transport characteristics), and biological properties (cell proliferation and osteogenic differentiation). Finally, RNA sequencing was employed to elucidate the mechanisms by which the novel scaffolds regulated cell behavior. The NG-NP structure exhibited the advantage of a low elastic modulus combined with high strength and showed anisotropic characteristics in mechanical properties and mass transport characteristics closely matching those of cancellous bone. The strength and permeability of the NG-NP structure could be flexibly regulated by adjusting its structural orientation to meet specific requirements for bone regeneration at bone defect sites. Curvature change introduced by the cosine term induced cytoskeletal reorganization and activated the integrin-mediated MEK/ERK signaling pathway. Compared with the single-topology scaffolds, the dual-topology fusion scaffold NG-NP regulated cell behavior by activating the Wnt/β-catenin signaling pathway. Overall, the dual-topology fusion orthotropic scaffold NG-NP proposed in this study exhibited anisotropic characteristics and biomimetic properties in structure and function. This study provided important theoretical and experimental bases, as well as feasible design strategies for scaffolds required in bone regeneration.