Calcium phosphate coatings with differentiated crystallinity on polyamide scaffolds enable Dual-Stage bone regeneration

• Dual CaP coatings enable staged bone regeneration. • Burst ions boost early osteogenesis & cell recruitment. • Sustained ions enhance long-term bone mineralization. • Crystallinity dictates ion release rate and biofunction. • A precision tool for sequential repair of bone defects. The exploration of calcium phosphate (CaP) scaffold coatings with different degradability will benefit bone regeneration at specific stages. Herein, we engineered non-degradable polyamide 66 (PA66) scaffolds functionalized with two CaP coatings, i.e., fast-degrading amorphous calcium phosphate oligomers (CPO) were coated on PA66 mesh to form the PAC scaffolds, and slow-degrading crystalline nanohydroxyapatite spheres (HAS) were coated on PA66 mesh to form the PAH scaffolds. The CPO coating on PAC scaffolds exhibited rapid CaP degradation and burst ion release, accelerating early-stage osteogenesis by promoting stem cell recruitment and collagen deposition. In addition, the transient calcium-rich microenvironment generated by the CPO coating also elicited early angiogenic responses, which may synergistically facilitate rapid defect bridging. In contrast, the HAS coating on PAH scaffolds demonstrated gradual CaP dissolution, supporting sustained mineralization and long-term bone remodeling. Both CaP coatings improved hydrophilicity and mechanical strength, while the non-degradable PA66 scaffold mesh with structural integrity maintained a space for bone regeneration and reconstruction. In vivo evaluations confirmed the PAC scaffolds to initiate early osteogenesis (significant BV/TV increase at 4 weeks), whereas the PAH scaffolds achieved comparable bone repair by 12 weeks through sustained ion release. This crystallinity-driven strategy could jointly establish spatiotemporal ion release when needed as a precision tool for bone regeneration, meeting the clinical requirement for biomaterials that sequentially support both repair and remodeling phases of large bone defect healing.