Synergistic peptide–organic matrix enhances mineralization of biomimetic scaffolds for bone regeneration

Biomimetic mineralized composites engineered <i>via</i> organic matrix templating show promise for bone repair but suffer from poor mineralization and imbalanced mechanical-biological performance. This study synergistically regulated biomolecules and organic matrix properties to enhance <i>in situ</i> mineralization, thereby improving mechanical strength and osteogenic potential. A nucleation-domain containing peptide (HGRGEAFDY) screened through molecular dynamics simulation was integrated into the gelatin matrix to prepare biomimetic materials with enhanced mineralization performance. The influence of peptide and organic matrix properties on mineralization capacity and saturation of <i>in situ</i> mineralization (SIM) was investigated. Results demonstrated that peptides with characteristic nucleation domains can boost mineralization by providing more nucleation sites and strengthening organic-inorganic interactions. Meanwhile, matrix compactness negatively correlated with mineralization capacity and SIM. Combined modulation of peptide nucleation ability and matrix compactness can enhance the SIM of the matrix, increasing the amount of minerals while improving mechanical properties. The biomimetic composites/scaffolds with mineralization enhancement by peptide-organic matrix regulation were evidenced to promote cell proliferation and osteogenic differentiation, and <i>in vivo</i> bone regeneration by upregulating BMP2 gene expression. This study provides valuable insights into the design of biomimetic mineralized materials and offers strategies for developing bone repair scaffolds with improved mechanical and biological performance.