Biomimetic mineralized collagen nanostructures orchestrate osteogenesis and osteoimmunomodulation to improve osseointegration of titanium alloy microporous interfaces

Inadequate osseointegration remains a major clinical challenge in joint replacement surgery, frequently resulting in aseptic loosening and necessitating revision procedures. Herein, we present a novel approach that combines 3D printing, tissue engineering, and biomimetic technologies to address this problem. We developed a novel surface modification strategy to engineer two functional interfaces on microporous titanium implants (PTi): an intrafibrillar/extrafibrillar mineralized collagen interface (I-EMC/PTi) and an extrafibrillar mineralized collagen interface (EMC/PTi). The fabrication process involves dopamine self-polymerization, covalent collagen immobilization, and subsequent biomineralization through ion-mediated crystallization and polymer-induced liquid-precursor techniques. This hierarchical method achieves comprehensive functionalization of the microporous titanium surface. The engineered hybrid interfaces markedly improved the surface properties of PTi, including roughness, hydrophilicity, and protein adsorption capacity. Notably, the I-EMC/PTi interface exhibited nanostructural features resembling natural bone tissue and optimal surface roughness, demonstrating superior osteoinductive properties. Moreover, this interface modulates the bone immune microenvironment by promoting M2 macrophage polarization, thereby enhancing osteogenic differentiation of bone marrow mesenchymal stem cells. In vivo evaluation using a rabbit femoral condyle defect model confirmed that the I-EMC/PTi implant significantly promoted new bone formation and improved bone-implant integration, as quantitatively confirmed through micro-computed tomography and histological analyses. Overall, this study provides a promising strategy for constructing artificial implants with enhanced bioactivity and establishes a robust foundation for developing next-generation implant materials with enhanced clinical performance.