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

Abstract

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.

Mechanical Properties and In Vitro Behavior of Additively Manufactured and Functionally Graded Ti6Al4V Porous Scaffolds

“…Consequently, the proliferation rate of cells on these scaffolds was markedly less. Although this immobilization behavior of the preosteoblast cells when seeded from small pore size region was observed in the previous studies of Nune et al [38,39], the underlying reason for this behavior is still unknown. The smallest pore size in our scaffolds were 940 µm which is larger than the suggested pore size (100-300 µm) for cell colonization and migration [62,63].…”

“…In recent years, additively manufactured gradient structures for tissue engineering have been studied [37][38][39]41,44,64,65]; however these studies either focused on the mechanical properties or biological response independently. In this work, the biological and mechanical responses were assessed simultaneously allowing us to study the overall impact of the designed geometry of the scaffolds.…”

“…A number of studies have investigated the mechanical or biological response of metallic-based gradient porous designs produced by additive manufacturing [37][38][39][40][41][42][43][44][45]. The majority of these studies focused on gradient structures generated by abrupt changes between layers based on change in strut diameter or unit cell volume.…”

“…They concluded that continuous variation between layers are ideal to minimize the stress concentration at the interface. Nune et al [38,39] investigated the osteoblastic functions of the scaffolds designed using Li et al [37] work, based on gradient rhombic dodecahedron created by changing the unit volume between layers. Although their work showed promising results on cellular activity when cells were seeded from large pore side (1000 µm), there was no complementary study on the mechanical properties and therefore the adverse effect of discontinuity between layers on the mechanical properties were not covered.…”

Advancements in three-dimensional titanium alloy mesh scaffolds fabricated by electron beam melting for biomedical devices: mechanical and biological aspects

“…463 tion of pores can repair and reconstruct more than one tissue, even though the microenvironment varies for different tissues [1]. For instance, functionally graded porous titanium alloy fabricated to meet the requirements of tissue engineering and to reduce stress shielding and high energy absorption indicated that the structure facilitated flow of nutrients and cell proliferation across the entire structure [101,102]. It was concluded that the REVIEWS .…”