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.
Impact Statement
Current polymeric scaffolds for bone tissue engineering frequently fail to replicate the dynamic mechanical microenvironment required for optimal tissue remodeling. This critical review bridges the gap between foundational fracture healing mechanics and advanced biomaterial design by proposing a “mechanobiological triad”—encompassing fixation mechanics, scaffold architecture, and host biological factors—as a governing framework for clinical success. We systematically evaluate how emerging technologies, including 4D printing, piezoelectric materials, and machine-learning-driven design, can create mechanically adaptive systems that actively guide cellular differentiation rather than serving as passive void fillers. This article serves as a translational roadmap for designing the next generation of bioinspired scaffolds that synchronize mechanical stiffness and bioactivity with the temporal stages of bone repair.
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