Multifunctional polycation-collagen scaffold via biomimetic mineralization: from molecular mechanism to potential...

Mineralized collagen (MC) serves as a fundamental structural motif during hard tissue development, directing the primary orientation of mineral crystals. To replicate these intricate hierarchical structures, recent studies have focused on both interfibrillar and intrafibrillar crystallization of type I collagen. Beyond conventional polyanions, alternative synthesis strategies utilizing polycations to stabilize amorphous precursors have been proposed. In this study, polyethylenimine (PEI) as a novel polycation was investigated. Using collagen models, the structure and properties of the PEI conjugated collagen (PC) scaffolds were characterized through transmission electron microscopy, atomic force microscopy, and complementary techniques. The PC scaffolds demonstrated successful biomineralization, enhanced resistance to collagenase degradation, and potent contact-based antimicrobial activity against Staphylococcus aureus, Streptococcus mutans, and Escherichia coli. Molecular dynamics simulation revealed underlying mechanisms of PC-guided biomineralization, including osmotic pressure fluctuations and localized phosphate ion enrichment. Furthermore, mineralized PC significantly upregulated the expression of osteogenesis-related genes in bone marrow mesenchymal stem cells. Collectively, these findings establish the self-mineralizing PC scaffold as a promising biomaterial combining antimicrobial, anti-enzymatic, and osteoinductive properties, thus presenting strong potential for treating complex hard tissue defects. Additionally, theoretical analyses of electrostatic equilibrium and osmotic pressure in cationic PC may broaden the spectrum of MC stabilizers.