Bio-surface coated titanium scaffolds with cancellous bone-like biomimetic structure for enhanced bone tissue regeneration

In view of the fact that titanium (Ti)-based implants still face the problem of loosening and failure of the implants caused by the slow biological response, the low osseointegration rate and the implant bacterial infection in clinical application, we designed a cancellous bone-like biomimetic Ti scaffold using the template accumulated by sugar spheres as a pore-forming agent. And based on a modified surface mineralization process and mussel-like adhesion mechanism, a silicon-doped calcium phosphate composite coating (Van-pBNPs/pep@pSiCaP) with Vancomycin (Van)-loaded polydopamine (pDA)-modified albumin nanoparticles (Van-pBNPs) and cell adhesion peptides (GFOGER) was constructed on the surface of Ti scaffold for mimicking the extracellular matrix (ECM) microenvironment of natural bone matrix to induce greater tissue regeneration. The in vitro study demonstrated that this porous Ti scaffold with functional bio-surface could distinctly facilitate cell early adhesion and spreading, and activate the expression of α2β1 integrin receptor on the cell membrane through promoting the formation of focal adhesions (FAs) in bone marrow stromal cells (BMSCs), thus mediating greater osteogenic cell differentiation. And it could also effectively inhibit the adhesion and growth of Staphylococcus epidermidis, exhibiting good antibacterial properties. Moreover, the Van-pBNPs/pep@pSiCaP-Ti scaffolds showed enhanced in vivo bone-forming ability due to the contributions of bioactive chemical components and the natural cancellous bone-like macrostructure. This work offers a promising structural and functional bio-inspired strategy for designing metal implants with desirable ability of osteoinduction synergistically with antibacterial efficacy for promoting bone regeneration and infection prevention simultaneously. STATEMENT OF SIGNIFICANCE: This manuscript describes a new method for making porous Ti scaffolds with a natural cancellous bone-like structure. Besides, a functional bio-surface was constructed on the bionic structure, mimicking some of the functions of the collagen-rich organic matrix and inorganic CaP nanocrystallites of native ECM of bone in chemical components and biological activities. This interconnected inter-pore opening structure encouraged the migration of cells among open macro-pores within the scaffold. In addition, the functionalized surface not only improved early cell adhesion, spreading, stimulated greater osteogenic differentiation of bone-forming cells, but also endowed the scaffold with excellent antibacterial effect. The biomimetic metal implant with multiple biomedical functions designed in this study has a great clinical application potential. This study represents a feasible method for the preparation of biomimetic structure of metal implants and the improvement of their surface biological activity.