Hierarchically Biomimetic Scaffolds with Anisotropic Micropores and Nanotopological Patterns to Promote Bone Regeneration via Geometric Modulation

Structural engineering is an appealing means to modulate osteogenesis without the intervention of exogenous cells or therapeutic agents. In this work, a novel 3D scaffold with anisotropic micropores and nanotopographical patterns is developed. Scaffolds with oriented pores are fabricated via the selective extraction of water-soluble polyethylene oxide from its poly(epsilon-caprolactone) co-continuous mixture and uniaxial stretching. The plate apatite-like lamellae are subsequently hatched on the pore walls through surface-induced epitaxial crystallization. Such a unique geometric architecture yields a synergistic effect on the osteogenic capability. The prepared scaffold leads to a 19.2% and 128.0% increase in the alkaline phosphatase activity of rat bone mesenchymal stem cells compared to that of the scaffolds with only oriented pores and only nanotopographical patterns, respectively. It also induces the greatest upregulation of osteogenic-related gene expression in vitro. The cranial defect repair results demonstrate that the prepared scaffold effectively promotes new bone regeneration, as indicated by a 350% increase in collagen I expression in vivo compared to the isotropic porous scaffold without surface nanotopology after implantation for 14 weeks. Overall, this work provides geometric motifs for the transduction of biophysical cues in 3D porous scaffolds, which is a promising option for tissue engineering applications. This study presents a 3D scaffold featuring anisotropic micropores and nanotopographical patterns to modulate osteogenesis. The scaffold, fabricated through selective extraction, uniaxial stretching, and surface-induced epitaxial crystallization, possesses a unique geometric architecture, which significantly enhances bone mesenchymal stem cell proliferation and osteogenic differentiation, leading to effective cranial defect repair and promising implications for tissue engineering applications. image