Biomimetic Bone Tissue Engineering Scaffolds Combined with Physical Stimulation to Reconstruct Piezoelectric Network for Functional Regeneration in Critical Bone Defects

In addition to supporting and protecting mobility, bone is essential for regulating systemic homeostasis. Large bone defects have always been a clinical challenge because of their complicated composition and structure, which makes them difficult to repair on their own. Currently, clinical operations employ primarily autologous, allogeneic, and synthetic bone grafting methods, which are still limited by factors such as donor scarcity, complications from infections, and market acceptance. Thus, novel biomimetic artificial bone tissue engineering scaffolds can be created by designing and regulating the composition and structure of materials, drawing inspiration from the intrinsic properties of genuine bone tissue. The combined application of bioactive substances and biomaterials in bone repair has achieved multiple satisfactory clinical outcomes. In this Account, based on the principles of bionic tissue engineering, we constructed various bone repair scaffolds through multidimensional approaches and systematically evaluated their capabilities in vascular regeneration, nerve ingrowth, and osteogenesis. The technological development of scaffolds demonstrated a distinct progressive relationship: The initial stage focused on the bionics of natural bone tissue’s matrix and structure; the advanced stage integrated bioactive components like BMP2 to achieve functional osteoinduction; the deepening stage introduced piezoelectric signals to directly regulate the osteogenic function of scaffolds, while simultaneously controlling angiogenesis and nerve ingrowth to indirectly promote bone repair and regeneration. Ultimately, an innovative bone repair paradigm based on “Piezoelectric Network Theory” was proposed. Extracellular matrix (ECM) engineered scaffolds were reconstructed to provide endogenous effects through surface morphology modulation and bioactive component modification. The synergistic responses between endogenous effect and exogenous physical stimulation achieve rapid repair of a variety of large segmental bone defects in various areas. This advancement will establish new theoretical foundations for functional bone reconstruction and significantly enhance the treatment efficacy for large segmental bone defects.