Hierarchical multifunctional cellular materials for implants with improved fatigue resistance and osteointegration

Chronic or degenerative diseases affecting the lumbar spine, commonly referred to as low back pain (LPB), are a major cause of dysfunction, pain, and disability worldwide. According to the Global Burden of Disease (GBD) report of 2019, LPB affects over half a billion people, severely limiting their well-being and lifestyle. Unfortunately, these numbers have been steadily increasing over the last decade, with a rise of more than 15%, mainly due to demographic aging of the population, making it a significant socioeconomic global issue. When conservative treatments such as medications, drugs, and injections fail to alleviate the symptoms, surgical interventions become necessary. Spinal surgeries have become increasingly common and account for 40% of the top ten surgical procedures in the United States alone. As a result, the global market for spinal implants and medical orthopedic devices has been growing at a compound annual growth rate (CAGR) of 5.0% in the United States. Degenerative disc diseases, herniated intervertebral discs, and spondylolisthesis are among the most common problems requiring implant surgery, with lumbar interbody fusion cages or total disc replacements being the most common options. These surgical techniques often utilize a metal endplate or hollow cage as a load-bearing structure to ensure correct load transmission and biomechanical spinal functionality. Currently, endplates for total disc replacement are produced using subtractive manufacturing techniques from bulk biomedical-graded metal alloys like Ti-6Al-4V. The endplates are inserted between two adjacent vertebral bodies, where bone ingrowth and implant fusion are necessary. However, the elastic properties of bulk metals and bone tissue do not match, resulting in stress-shielding phenomena, implant loosening, or implant subsidence. These complications frequently necessitate surgical revision of the implant, which not only impacts the daily activities of the patients but also has a relevant economic impact. Therefore, researchers are exploring alternative design and manufacturing strategies to develop next-generation prosthetic devices that overcome these challenges. Metal additive manufacturing (MAM), particularly Laser-Powder Bed Fusion (L-PBF), has revolutionized the fabrication of specialized components with complex shapes, including architected cellular materials - a novel class of engineered materials with tunable mechanical properties. The biomedical field is a prime example of where lattice application has proved beneficial. MAM provides numerous advantages, including patient-specific customization, a vast design space, and reduced stress shielding. However, issues with structural integrity, lack of AM-specific norms, and the need for fine-tuning process optimizations are still hindering MAM's widespread adoption on the international market. An essential issue that requires resolution is the impact of process-induced flaws on the fatigue behavior of components made of L-PBF lattices. Despite a growing body of scientific literature on the fatigue behavior of lattice unit cells, little attention has been given to the function of fatigue at a millimetric scale, specifically the role of sub-unital lattice elements such as struts and junctions. As fatigue is highly localized, understanding primary fatigue behavior and fracture mechanisms at a strut scale may be critical to addressing the aforementioned problems. Moreover, designing proper prosthetic devices requires fulfilling both biomechanical and biological requirements, leading to a bottleneck in component quality. Proper tuning of osteointegration often requires large porosity and small strut dimensions, approaching the limits of industrial 3D printers. This increases the likelihood of manufacturing lattices with unconnected struts, drosses, parasitic masses, and severe deviations from the nominal as-designed geometries, leading to highly susceptible components under fatigue. To address these challenges, combined approaches with bone tissue engineering may be advantageous. Biopolymers from natural sources, such as silk fibroin and collagen derivatives (i.e., gelatin), are widely used for bone-filler applications due to their exceptional biological properties. These polymers can create highly interconnected biodegradable porous 3D scaffolds suitable for cell differentiation towards an osteogenic phenotype, such as in the form of foams. These foams can be embedded into metal lattice structures, resulting in a hybrid composite device that simultaneously fulfills the load-bearing, fatigue, and osteointegrative requirements that a spinal prosthetic device necessitates. This thesis work covers a range of topics mentioned above. Firstly, an introductory theoretical background is presented in Chapter I, followed by experimental findings which are presented in three different chapters. Chapter II is dedicated to the fatigue behavior of L-PBF Ti-6Al-4V sub-unital lattice elements in the form of miniaturized dog-bone specimens that mimic struts and nodes. This chapter is divided into four sections. The first section investigates the fatigue strength of strut-like specimens based on their building orientations at four different angles with respect to the printing job plate. Morphological features of the miniaturized specimens such as average and minimum cross-section, eccentricity, waviness, and surface texture are correlated with fatigue strength. The role of inner and surface defects, such as lack-of-fusion (LoF) and gas holes, is also considered to explain the main failure mechanisms. The impact of building orientation on the printing quality of the specimens is highlighted, with an increase in surface roughness and defectiveness as the printing angle decreases, resulting in a shorter fatigue life for miniaturized struts. In the second section, the fatigue effect is studied across different fatigue regimes. The role of the mean stress effect is assessed using the Haigh diagram, which reveals an increase in fatigue life moving towards compressive loading regimes. The effect of the printing angle is also investigated, showing different trends according to the different stress ratios, suggesting different fatigue failing mechanisms. The third section introduces strut-junction miniaturized specimens and evaluates their fatigue behavior according to building orientations. Horizontal specimens show an increased fatigue life compared to their thin strut counterparts, and different morphological outcomes are highlighted, including improved surface quality even at lower angles, possibly related to the node acting as an additional supporting structure. The fourth section presents a design-led compensation strategy for sub-unital lattice specimens, aimed at reducing as-designed/as-built deviations. This systematic decrease in geometrical mismatch suggests potential new design strategies for fatigue enhancement. In Chapter III, bone tissue engineering strategies are explored for the design of foam scaffolds as bio-fillers for lattice-based design. The feasibility of the polymer-metal composite is assessed, using an N2O-based gas foaming technique to fabricate silk fibroin and silk fibroin/gelatin porous scaffolds infilled into a cubic L-PBF Ti-6Al-4V lattice structure. The adhesion at the polymer/metal interface is assessed, with simultaneous electrowetting, showing promise for better and more intimate contact on the outermost surface of the lattice struts. A statistical-based analysis of the foam porosity is then carried out, aimed at optimization towards osteointegration improvement. Selected foams are biologically evaluated, revealing good cell adhesion and differentiation towards an osteogenic phenotype. Chapter IV reports on two different strategies for the design of a Ti-6AL-4V L-PBF lattice-based endplate for total disc replacement. The first strategy focuses on homogenized-based topology optimization, designing an octet-truss prosthetic device with a graded structure and a cell size suitable for polymeric infilling. The second strategy aims at optimizing octet-truss lattice components for fatigue, evaluating the optimal building orientation for the specimens. Experimental results reveal an improvement in the fatigue life of three-point bending test specimens, suggesting the potential of the proposed model. In Chapter V, the major takeaways of this thesis work are discussed, highlighting important advancements in understanding the fatigue behavior of lattice structures and the development of novel hybrid strategies for the design of biomedical devices, with a particular focus on spinal orthopedics. Future possible directions for research are also explored.