Mussel-inspired bifunctional chimeric peptides macromolecules functionalize 3D-printed porous scaffolds for enhanced antimicrobial and osseointegration properties in bone defect repair.

Polyetheretherketone (PEEK) is a promising material for bone defect repair due to its superior mechanical properties and chemical stability. However, its limited bioactivity and susceptibility to infection hinder its clinical use. To address these limitations, we developed antibacterial and osteogenic bifunctional chimeric peptides (CP) and integrated them onto 3D-printed PEEK scaffolds (3DP) using the adhesive properties of 3,4-dihydroxy-L-phenylalanine (DOPA). The CP, composed of antimicrobial peptide (GL13K) and osteogenic peptide (PFS) linked by DOPA, enhances bacterial membrane disruption while promoting bone marrow mesenchymal stem cell (BMSCs) adhesion and osteogenic differentiation. Through DOPA-mediated attachment, a hydrophilic and stable layer is formed on the scaffold surface via a simple immersion process. In vitro studies showed that CP@3DP effectively destroys bacterial membranes of Staphylococcus aureus and Escherichia coli, while promoting BMSCs adhesion, proliferation, and differentiation. In a rat skull defect model infected with S. aureus, CP@3DP demonstrated synergistic antibacterial effects and enhanced bone regeneration. Micro-CT imaging and histologic analysis confirmed that CP@3DP was firmly bound to host bone. This study highlights the potential of DOPA as a versatile adhesion molecule and the CP's bifunctional design for bone defect repair in infected environments, offering a novel approach for tissue engineering applications.