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, we developed a novel three-dimensional (3D) scaffold with anisotropic micropores and nanotopographical patterns. Scaffolds with oriented pores were fabricated via the selective extraction of water-soluble polyethylene oxide (PEO) from its poly(ε-caprolactone) (PCL) co-continuous mixture and uniaxial stretching. The plate apatite-like lamellae were subsequently hatched on the pore walls through surface-induced epitaxial crystallization. Such a unique geometric architecture yielded a synergistic effect on the osteogenic capability. The prepared scaffold led to 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 induced the greatest upregulation of osteogenic-related gene expression in vitro. The cranial defect repair results demonstrated that the prepared scaffold effectively promoted 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 article is protected by copyright. All rights reserved.