No abstract

We elucidate here process-structure-property relationships in implantable biomaterials processed by rapid prototyping approaches that are based on the principle of additive manufacturing. The conventional methods of fabrication of biomedical devices including freeze casting and sintering are limited because of difficulties in adaptation at the host site and mismatch in micro/ macrostructure, mechanical and physical properties with the host tissue. Moreover, additive manufacturing has the advantage of fabricating patient-specific designs, which can be obtained from the computed tomography scan of the defect site. The discussion here comprises two partsthe first part briefly describes the evolution and underlying reasons that have led to 3D printing of scaffolds for tissue regeneration. The second part focuses on biocompatibility and mechanical properties of 3D scaffolds, fabricated by different approaches. The article concludes with a discussion on functionally graded scaffolds and vascularisation of 3D porous scaffolds that are envisaged to meet the requirements of the biomedical industry. In general, the mechanical properties of 3D printed scaffolds are governed by pore architecture, pore volume and percentage porosity. To ensure long-term endurance and the ability to withstand abrupt impact, it is important that the fabricated materials have a good combination of strength and energy absorption capability. While scaffolds with high interconnected porosity are preferred for tissue regeneration, such structures lack adequate mechanical strength and energy absorption capability. These mutually opposing requirements of high porosity and mechanical strength in conjunction with high energy absorption have hindered the application of 3D scaffolds as biomedical devices. In this regard, functionally graded 3D structures with high strength and energy absorption are potentially attractive for biomedical devices.

The cellular activity, biological response, and consequent integration of scaffold-cell construct in the physiological system are governed by the ability of cells to adhere, proliferate, and biomineralize. In this regard, we combine cellular biology and materials science and engineering to fundamentally elucidate the interplay between cellular activity and interconnected three-dimensional foamed architecture obtained by a novel process of electron beam melting and computational tools. Furthermore, the organization of key proteins, notably, actin, vinclulin, and fibronectin, involved in cellular activity and biological functions and relationship with the structure was explored. The interconnected foamed structure with ligaments was favorable to cellular activity that includes cell attachment, proliferation, and differentiation. The primary rationale for favorable modulation of cellular functions is that the foamed structure provided a channel for migration and communication between cells leading to highly mineralized extracellular matrix (ECM) by the differentiating osteoblasts. The filopodial interaction amongst cells on the ligaments was a governing factor in the secretion of ECM, with consequent influence on maturation and mineralization.

Three-dimensional cellular scaffolds are receiving significant attention in bone tissue engineering to treat segmental bone defects. However, there are indications of lack of significant osteoinductive ability of three-dimensional cellular scaffolds. In this regard, the objective of the study is to elucidate the interplay between bone morphogenetic protein (BMP-2) and osteoblast functions on 3D mesh structures with different porosities and pore size that were fabricated by electron beam melting. Self-assembled dendritic microstructure with interconnected cellular-type morphology of BMP-2 on 3D scaffolds stimulated osteoblast functions including adhesion, proliferation, and mineralization, with prominent effect on 2-mm mesh. Furthermore, immunofluorescence studies demonstrated higher density and viability of osteoblasts on lower porosity mesh structure (2 mm) as compared to 3- and 4-mm mesh structures. Enhanced filopodia cellular extensions with extensive cell spreading was observed on BMP-2 treated mesh structures, a behavior that is attributed to the unique self-assembled structure of BMP-2 that effectively communicates with the cells. The study underscores the potential of BMP-2 in imparting osteoinductive capability to the 3D printed scaffolds.

The objective of the study described here is to fundamentally elucidate the biological response of 3D printed Ti-6Al-4V alloy mesh structures that were surface modified to introduce titania nanotubes with an average pore size of ∼80 nm via an electrochemical anodization process from the perspective of enhancing bioactivity. The bioactivity of the mesh structures were analyzed through immersion test in simulated body fluid, which confirmed the nucleation and growth of fine globular nanoscale apatite on the nanoporous titania-modified (anodized) mesh structure surface, and agglomerated apatite with fine flakes of apatite crystals on as-fabricated mesh structure surface, that were rich in calcium and phosphorous. The cellular activity of bioactive anodized mesh structure was explored in terms of cell-material interactions involving adhesion, proliferation, synthesis of extracellular and intracellular proteins, differentiation, and mineralization. Cells adhered with a sheet-like morphology on as-fabricated mesh structure, whereas, on anodized mesh structure, numerous filopodia-like cellular extensions interacting with nanotube pores were observed. The formation of a bioactive nanoscale apatite, cell-nanotube interactions as imaged via electron microscopy, higher expression of proteins (actin, vinculin, fibronectin, and alkaline phosphatase (ALP)), and calcium content points toward the determining role of anodized mesh structure in modulating osteoblasts functions. The unique combination of nanoporous bioactive titania and interconnected porous architecture of anodized titanium alloy mesh structure provided a multimodal roughness surface ranging from nano to micro to macroscale, which helps in attaining strong primary and secondary fixation of the implant device along with the pathway for supply of nutrients and oxygen to cells and tissue.