Mechanobiological Design of Bioinspired Polymeric Scaffolds for Bone Regeneration.
Bone regeneration presents a significant clinical challenge due to the complex interplay between biological processes and the local mechanical environment. While polymeric scaffolds are widely utilized for their tunable physicochemical properties, traditional designs often fail to replicate the dynamic mechanical cues required for optimal tissue remodeling. This review critically examines the mechanobiological design of bioinspired polymeric scaffolds. We first categorize native bone mechanics and the role of mechanical stimuli-such as stiffness, fluid shear, and stability-in regulating the fracture healing cascade. We then bridge these biological principles with advanced fabrication strategies, analyzing how natural, synthetic, and composite polymers can be engineered to mimic the hierarchical stiffness and bioactivity of native bone. Furthermore, we discuss the role of computational modeling (e.g., Finite Element Analysis) in predicting scaffold performance and highlight emerging technologies, including 4D printing and piezoelectric scaffolds, which offer time-dependent and mechano-electrical adaptability. Finally, we address current barriers to clinical translation and propose future directions for mechanically adaptive systems that actively guide regeneration.