Osteoblast functions in functionally graded Ti-6Al-4 V mesh structures.

We describe here the combined efforts of engineering and biological sciences as a systemic approach to fundamentally elucidate osteoblast functions in functionally graded Ti-6Al-4 V mesh structures in relation to uniform/monolithic mesh arrays. First, the interconnecting porous architecture of functionally graded mesh arrays was conducive to cellular functions including attachment, proliferation, and mineralization. The underlying reason is that the graded fabricated structure with cells seeded from the large pore size side provided a channel for efficient transfer of nutrients to other end of the structure (small pore size), leading to the generation of mineralized extracellular matrix by differentiating pre-osteoblasts. Second, a comparative and parametric study indicated that gradient mesh structure had a pronounced effect on cell adhesion and mineralization, and strongly influenced the proliferation phase. High intensity and near-uniform distribution of proteins (actin and vinculin) on struts of the gradient mesh structure (cells seeded from large pore side) implied signal transduction during cell adhesion and was responsible for superior cellular activity, in comparison to the uniform mesh structure and non-porous titanium alloy. Cells adhered to the mesh struts by forming a sheet, bridging the pores through numerous cytoplasmic extensions, in the case of porous mesh structures. Intercellular interaction in porous structures provided a pathway for cells to communicate and mature to a differentiated phenotype. Furthermore, the capability of cells to migrate through the interconnecting porous architecture on mesh structures led to colonization of the entire structure. Cells were embedded layer-by-layer in the extracellular matrix as the matrix mineralized. The outcomes of the study are expected to address challenges associated with the treatment of segmental bone defects and bone-remodeling through favorable modulation of cellular response. Moreover, the study provides a foundation for a new branch of functionally graded materials with interconnected porous architecture.