Biomimetic mineralized chiral structural films guiding for enhanced cranial bone regeneration

Bone defect repair remains a significant clinical challenge due to the intricate hierarchical and mineralized structure of native bone tissue. Inspired by the mineralized chiral organization of collagen fibrils in bone, this study presents a biomimetic strategy for bone regeneration using mineralized helicoidal structural cellulose nanocrystal (CNC) films. These chiral CNC films serve as a soft template to direct the mineralization of amorphous calcium carbonate (ACC), a reactive and soluble precursor, resulting in mechanically robust mineralized cellulose nanocrystal (MCNC). This approach recapitulates the structural guidance and dynamic mineralization process of natural bone healing. In vitro , the resulting mineralized films significantly promoted both angiogenic and osteogenic differentiation. In a mouse cranial defect model, MCNC films markedly enhanced new bone formation and facilitated vascular-bone tissue integration. Transcriptomic analysis showed gene and protein networks associated with mineralization-vascularization reactions, including cell adhesion, bone formation, and angiogenesis. The enriched signaling pathways include PI3K-AKT signaling pathway, MAPK signaling pathway, Calcium signaling pathway and Notch signaling pathway, clarifying the complex molecular interactions and signal cascades mediated by MCNC films. This work demonstrates that integrating chiral CNC templates with ACC precursors creates a tunable, biomimetic platform that synergistically combines structural order with bioactive mineralization, offering a promising strategy for advanced bone regenerative materials. • Chiral cellulose nanocrystals (CNC) serve as templates to direct the mineralization of amorphous calcium carbonate, effectively mimicking the structural and mineral dynamics of bone. • The mineralized CNC (MCNC) films exhibit enhanced mechanical strength and toughness, providing robust support for bone regeneration. • By synergistically promoting osteogenesis and angiogenesis, MCNC substrates significantly enhance the healing of bone defects.