Browsing by Author "Gall, Ken"

Additive manufacturing (AM, or 3D printing) has revolutionized fabrication of three dimensional (3D) parts with increased control over design at macro/meso-scale (part scale geometry, porous topology) and micro/nanoscale (topography). AM has enabled fabrication of metallic, polymeric, and ceramic scaffolds with complex porous architectures which were not previously achievable with traditional manufacturing methods. In particular, selective laser melting (SLM) has emerged as a leading technology for fabrication of porous metallic scaffolds for biomedical and other applications. Titanium alloy (Ti6Al4V) scaffolds are of interest due to the material’s high strength, corrosion resistance, and biocompatibility. Architecting porous scaffolds with tunable properties is highly relevant for load-bearing medical implants, including treatment of bone defects. Although established relationships exist for metallic foams, the complex topologies enabled by AM necessitate further characterization. In particular, investigation of processing-structure-property relationships for novel sheet-based architectures produced via SLM where topology strongly influences performance. Thus, the overall objective of this work is to develop fundamental topology driven processing-structure-property relationships considering tradeoffs between strength, fatigue resistance, and osseointegrative behavior of SLM titanium scaffolds.

3D printing has seen an explosion of interest and growth in recent years, especially within the biomedical space. Prized for its efficiency, ability to produce complex geometries, and facile material processing, additive manufacturing is rapidly being used to create medical devices ranging from orthopedic implants to tissue scaffolds. However, 3D printing is currently limited to a select few material choices, especially when one considers soft tissue replacement or augmentation. To this end, my research focuses on developing material systems that are simultaneously 1) 3D printable, 2) biocompatible, and 3) mechanically robust with properties appropriate for soft-tissue replacement or augmentation applications. Two systems were developed toward this goal: an interpenetrating network (IPN) hydrogel consisting of covalently crosslinked poly (ethylene glycol) diacrylate (PEGDA) and ionically crosslinked brown sodium alginate, and semi-crystalline thiol-ene photopolymers containing spiroacetal molecules in the polymer main-chain backbone. In addition to successfully being incorporated into existing 3D printing systems (extrusion-deposition for the PEGDA-alginate hydrogel and digital light processing for the thiol-ene polymers) both systems exhibited biocompatibility and superior thermomechanical properties such as tensile modulus, failure strain, and toughness. This work offers two fully-developed, novel polymer platforms with outstanding performance; further, structure-property relationships are highlighted and discussed on a molecular and morphological level to provide material insights that are useful to researchers and engineers in the design of highly tuned and mechanically robust polymers.

The ability to change the design parameters of metallic lattice structures provides the control to optimize the interconnected porosity size to promote osseointegration and manipulate stiffness values to mimic bone, ideal for minimizing stress shielding. These benefits have caused a widespread proliferation of 3D printed porous metallic scaffolds in orthopedic implants, specifically Laser Powder Bed Fusion (LPBF). Once implanted, these devices experience complex stress states under physiological loading. To design these structures to mimic the mechanical behavior of bone, their performance under these conditions must be understood. The characterization of 3D printed metallic lattice structures’ compressive mechanical properties is well established, but the mechanical behavior of these structures under additional loading conditions requires further exploration. This research aims to define a method for characterizing LPBF metallic lattice structures’ mechanical properties in various physiologically relevant loading conditions and determine the stress state’s pure impact on the design parameters of metallic lattice structures to optimize the design process for practical applications. To achieve this goal, Ti6Al4V and Co28Cr6Mo metallic lattice structures were fabricated via LPBF, and monotonic tensile, compressive, compressive shear, and torsion testing was conducted to determine the mechanical behavior. The findings showed that sample geometry and test setup significantly impacted the mechanical properties of metallic lattice structures, which led to the design of a universal sample geometry that enabled the utilization of a single sample for tensile, compressive, and torsional testing. The impact of the stress state’s effect on sheet-based, strut-based, stochastic, and functionally graded metallic lattice structures was characterized.

With advancements in 3D printing, porous titanium implants have gained attention in the medical community as a suitable replacement for damaged bone. Additive manufacturing techniques like Selective Laser Melting (SLM) can create complex porous structures within the body of an implant that encourage osseointegration and result in implant stiffness that matches that of surrounding bone. This leads to better integration of the implant and decreases the risk complications due to stress shielding.

One concern with applying porous architectures to medical implants comes from the small size of the implants. Small porous devices can see boundary effects where a truncated pore is no longer contributing to the loading, which causes the porous material to be weaker than bulk properties would predict. As such, the ratio of the diameter of the loading cross-section to the unit cell size (D/u) becomes an important consideration when applying porous structures to load-bearing implants.

This study sought to find the saturation point of D/u, which is the point where the boundary effects are no longer significant and the properties of the porous material reflect bulk material properties. Three different porous architectures were tested in this study: gyroid-sheet, octet-truss, and stochastic-truss. Cubic unit cells ranging from 3x3x3mm to 12x12x12mm were applied to 10mm and 20mm diameter samples for each architecture, then samples were printed from Ti6Al4V powder using SLM. Specimens were then tested under compressive loading to determine compressive mechanical properties.

Testing revealed that the gyroid-sheet was the strongest and stiffest architecture, followed by the octet-truss and stochastic-truss architectures. Further analysis showed that the gyroid-sheet saturates at D/u≈3, while the octet-truss and stochastic-truss saturate at D/u≈5. The difference between the saturation points for the truss vs sheet-based architectures is likely due to the way the architectures are defined.

The gyroid-sheet is formed using a continuous sheet, so even when the pore is truncated it still contributes to loading. When a pore is truncated in the truss-based architectures, on the other hand, it no longer contributes to the loading. Because of this, the octet-truss and stochastic-truss architectures see much greater boundary effects, so more unit cells across the loading diameter are required to reach bulk material properties. This indicates that the gyroid-sheet is a suitable porous architecture to use in orthopedic implants.

Total joint arthroplasty (TJA) is the replacement of damaged or arthritic joints with synthetic components to improve patient mobility and quality of life. It is a highly effective procedure with a low rate of complications. However, due to the sheer volume of TJA operations, which is over a million per year in the U.S., there are tens of thousands of patients who experience severe complications, such as mechanical loosening, periprosthetic fracture, implant failure, and periprosthetic joint infection (PJI). Perhaps the most severe is PJI, which is an infection of the tissue surrounding the implant, generally as a result of a pathogen, primarily Staphylococcus aureus (S. aureus), entering the joint through the open wound during the surgical procedure. Although the immune system can usually eliminate invading pathogens effectively, the presence of a foreign body, in this case a synthetic joint, significantly reduces the concentration of bacteria required to induce infection due to the ability of bacteria to attach and grow on the surface of the implant. Over time this leads to pain, redness, swelling, and weakening of the joint that could necessitate amputation if untreated.The gold standard treatment for PJI is a two-stage exchange. In the first stage, the infected device is removed, and the infected tissue is debrided and irrigated to eliminate as much of the infection as possible. Then, a new device, called a spacer, is implanted into the joint in place of the original prosthetic. A spacer is an articulating device composed of poly(methyl methacrylate) (PMMA), commonly called bone cement, that releases antibiotics long-term to treat any remaining infected tissue. The advantage of PMMA over possible alternative biomaterials is 1) the ability to mix antibiotics into the cement before molding it into a desired shape, 2) a porous structure that enables antibiotics to leach from the matrix, and 3) sufficient mechanical strength to support partial load-bearing activity during the treatment period. Currently, the FDA has only approved pre-formed spacers with gentamicin, which limits them from treating bacteria that are resistant to gentamicin. While there used to be a mold available for surgeons to form PMMA spacers in the operating room with antibiotics of their choosing, that mold has since been recalled by the FDA. The spacer requires 6-12 weeks of antibiotic elution to eliminate the infection. After the surgeon determines the infection is gone, the second stage is the removal of the spacer and replacement with new sterile prosthetic components. The second stage is necessary since PMMA is too weak to support long-term full load-bearing activity, so the spacer must be replaced with stronger metal components to make sure the implant does not break, which could lead to serious consequences for the patient. The weak mechanical properties are a significant limitation of PMMA during the 6-12 week treatment period because the spacer frequently breaks when patients do not use ambulatory assist devices to facilitate mobility. A broken spacer can lead to soft tissue and bone damage and requires an additional surgery to replace the spacer. Several surgeries can be painful for the patient and extremely costly to the healthcare system. An ideal alternative spacer would have greater mechanical strength to reduce mechanical complications and the number of surgeries needed to treat PJI. In addition to poor mechanical properties, a second limitation of PMMA spacers is an inadequate antibiotic release profile to treat PJI. Since PMMA is non-biodegradable, antibiotics mixed throughout the cement cannot easily escape from the matrix to elute into the surrounding tissue. In fact, only antibiotics close to the implant surface are able to escape. This causes a burst release of antibiotics in the first few days of implantation with sub-therapeutic release thereafter. This can not only lead to persistence of the infection but can also induce antibiotic resistance, making it more challenging to treat the infection. Furthermore, PMMA cement sets with an exothermic reaction that is incompatible with many antibiotics. Currently only certain antibiotics can maintain their therapeutic efficacy following the exothermic reaction. Overall, PMMA spacers are an ineffective treatment for PJI due to poor mechanical properties and antibiotic release. An ideal alternative device would have greater mechanical strength and long-term release of therapeutic levels of antibiotics to effectively eliminate an infection. In this dissertation, I propose a novel spacer that can more effectively treat PJI vs. PMMA spacers due to the ability to modulate its antibiotic release to a desired profile, increase its mechanical strength tantamount to primary prosthetic components used in TJA, and minimize the ability of bacteria to attach and grow on its surface. The proposed technology takes advantage of the rapidly growing technology of additive manufacturing, also known as 3D-printing, which enables the manufacture of devices with complex structures. I propose 3D-printing joint devices with an internal reservoir to be loaded with a biodegradable carrier that releases antibiotics through 3D-printed channels that connect the reservoir to the surrounding tissue. While conventional manufacturing methods cannot make an internal reservoir with channels, 3D-printing enables precise control of the reservoir and channel geometry to tune the antibiotic release profile. A major advantage of this design over PMMA is the separation of the biomaterial that provides mechanical strength and the biomaterial that releases the antibiotics. In this way, I can 3D-print the device from a material with greater strength than PMMA, such as cobalt-chrome and titanium alloys, and I can load the reservoir with a biodegradable material that releases therapeutic levels of antibiotics over longer periods of time than PMMA. In chapter 3 of this dissertation, I assess the ability to modulate antibiotic release from 3D-printed reservoirs. I vary the geometry of reservoirs, including channel diameter, length, and quantity, to determine the effect on the in vitro antibiotic release from a carrier, in this case calcium sulfate, which is a biodegradable bioceramic frequently used as a bone void filler. Decreasing channel diameter and increasing channel length extends the release of antibiotics by extending the distance the antibiotics must diffuse through the carrier to reach the surrounding medium. To understand the mechanism of release, I develop a computational model of antibiotic release by simulating the reservoir as a 3D matrix in MATLAB. I model diffusion as a random walk and degradation as a progressive erosion over time. After fitting the diffusion and degradation constants to the data, the model effectively predicts the antibiotic release profile of a large range of reservoir geometries. This simple model can help rapidly prototype devices with a customized antibiotic elution profile to effectively treat PJI. In addition, I tested two carriers, calcium sulfate and tri-calcium phosphate, which degrades more slowly than calcium sulfate. Increasing the ratio of tri-calcium phosphate to calcium sulfate extends the release of antibiotics by decreasing the degradation of the bioceramic. Thus, modifying the properties of the carrier is another method to tuning antibiotic release in addition to reservoir geometry. Lastly, I studied the mechanical properties of 3D-printed reservoirs. Increasing the diameter of the channels decreases the mechanical strength of the reservoirs due to reduced structural support of the 3D-printed material. However, using 3D-printing, I can create lattice structures within the reservoir to provide additional mechanical support while still leaving sufficient volume to load an antibiotic-impregnated carrier. Overall, chapter 3 shows a multitude of methods to flexibly modulate both antibiotic release and mechanical strength to improve the ability to treat PJI vs. PMMA. In chapter 4, I study the ability of bacteria to form biofilm on the surface of different orthopedic materials, including 3D-printed metals that could potentially be used to make reservoirs. Biofilm is a conglomerate of microorganisms, most commonly S. aureus in PJI cases, that forms on the surface of an implant. Biofilm organizes in such a way to provide protection from the host immune system and antibiotics, making biofilm significantly harder to eliminate than planktonic, or free-floating, bacteria. It requires up to a thousand times higher concentration to eliminate bacteria in biofilm vs. planktonic bacteria. Therefore, in addition to high mechanical strength and long-term antibiotic release, another important property of an effective spacer is a reduced affinity for bacteria to form biofilm on the implant surface. I use a CDC biofilm reactor to model the in vivo conditions of PJI to grow bacteria on the surface of numerous relevant biomaterials. Using several quantitative methods, I found that biofilm grows more readily on non-polished 3D-printed metals and plastics, such as PMMA and ultra-high molecular weight polyethylene compared to polished and machined metals. To understand the mechanism, I measured the surface roughness and hydrophobicity of the materials. Materials with greater roughness and hydrophobicity developed more biofilm than smoother, hydrophilic materials. Metals are more hydrophilic and can be polished to a lower surface roughness value than PMMA. The data show that PMMA is not only mechanically weak and has a poor antibiotic release profile but also provides an additional surface for bacteria to readily form biofilm that can potentially worsen the existing infection. Taken together, this dissertation provides a comprehensive study of the advantages of hand-polished 3D-printed metal spacers with antibiotic-eluting reservoirs to effectively treat PJI vs. PMMA spacers due to 1) improved mechanical properties, 2) the ability to modulate antibiotic release to a wide range of release profiles, and 3) a reduced affinity of bacteria to form biofilm on the spacer surface.

Powder bed fusion (PBF), a popular metal 3D printing technique utilizing Selective Laser Melting (SLM) or Electron Beam Melting (EBM), has revolutionized the biomedical industry by providing uniquely customizable and precisely complex orthopedic implants that other production methods cannot offer. Titanium and cobalt alloys (Ti6Al4V and Co28Cr6Mo) are popular biocompatible materials utilized in orthopedic implants fabricated via PBF due to their high strength, low density, corrosion resistance, and suitability for osseointegration. Once implanted, the surfaces of these devices dictate short and long-term stability and durability through osseointegration and minimizing premature structural failure. While surface roughness and porosity can enhance osseointegration and stability, these surface topographies create areas for stress to concentrate. Implant strength and durability is then lowered, leading to an inherent trade-off between surface topography and the lifespan of orthopedic implants. This research aims to systematically evaluate the impact of relatively new and relevant surface topographies on short and long-term mechanical performance while applying appropriate American Society for Testing and Materials (ASTM) standards. To predict the short-term stability of an implant, Ti6Al4V devices with varying surface topographies manufactured through SLM underwent expulsion, subsidence, and shear testing. These mechanical tests evaluate the effects of topography, device size, porosity, and applied normal force at the bone-implant and solid-porous interface, while identifying trade-offs in static mechanical performance at these interfaces. When varying surface topographies, normal force was the most dominant predictor of expulsion, and a bigger device with more surface features displayed higher expulsion forces at increasing normal forces. When keeping a consistent gyroid topography and changing the unit cell size and wall thickness, the overall porosity was the statistically significant variable impacting expulsion, subsidence, and shear testing. A modeled 65% porous gyroid presented the best overall performance characteristics within the error of measurements. On the other hand, to predict long-term strength and durability, devices with varying material (Ti6Al4V versus Co28Cr6Mo), manufacturing techniques (SLM, EBM, and wrought), and surface finishes (“as printed”, blasted, machined, polished, and added surface porosity) were subjected to fatigue testing. Although varying fabrication methods impacted microstructure, data confirmed that refining the surface finish through mechanical post-processing was the predominant factor in improving fatigue strength across all sample groups. A critical surface roughness of about 0.2 µm was identified in which further decreasing the surface roughness was relatively ineffective in increasing fatigue strength. Conversely, further increasing gyroid thickness on the surface of SLM Ti6Al4V samples had a limited impact in decreasing fatigue strength. In conclusion, this research highlights potential tradeoffs for optimizing stability and lifespan of orthopedic implants through design and manufacture.

The following body of work was initiated from an in-depth clinical study examining the efficacy of 3D metal implants in treating critical sized defects (CSDs). While 3D metal implants successfully prevented amputations and restored function in the majority of patients, 26 % of cases failed and resulted in removal of the implant, with 50% of those patients proceeding to amputation. The study identified the following 3 mechanisms of failure: poor osseous integration, hardware malfunction, and bacterial infection. Each failure mechanism highlights an unmet need for research and improvement. Therefore, the purpose of this thesis is to improve the treatment of CSDs by providing preclinical data addressing mechanisms for failure – poor osseous integration, hardware malfunction, and bacterial infection. Aim 1 explored a novel method to improve osseousintegration by incorporating printed topography on the metal surface. The goal of the study was to understand how changing the surface roughness of 3D printed titanium either by surface treatment or artificially printing rough topography impacts the mechanical and biological properties of 3D printed titanium. Titanium tensile samples and discs were printed via laser powder bed fusion. Roughness was manipulated by post-processing printed samples or by directly printing rough features. Experimental groups in order of increasing surface roughness were Polished, Blasted, As Built, Sprouts, and Rough Sprouts. Tensile behavior of samples showed reduced strength with increasing surface roughness. MC3T3 pre-osteoblasts were seeded on discs and analyzed for cellular proliferation, differentiation, and matrix deposition at 0, 2, and 4 weeks. Printing roughness diminished mechanical properties such as tensile strength and ductility without clear benefit to cell growth. Roughness features were printed on mesoscale, unlike samples in literature in which roughness on microscale demonstrated an increase in cell activity. The data suggest that printing artificial roughness on titanium scaffold is not an effective strategy to promote osseous integration. Aim 2 developed a benchtop model to test various methods of fixation that can be used in conjunction with the 3D printed cage. The purpose of this study was to develop a simple and reproducible bending model that is compatible with a wide range of fixation devices and 3D printed spacers used in orthopedics so that they can be evaluated under equivalent conditions. A robust 4-point bending model was constructed by securing sawbones blocks with different orthopaedic fixation device constructs. Stress strain curves derived from a fundamental mechanics model were used to assess the effect of bone density, type of hardware (staple vs intramedullary beam), the use of dynamic compression, orientation of staples (dorsal vs plantar), and the use of 3D printed titanium spacers. All results were measured with respect to the stiffness and strength of pristine sawbones (without a cut) with identical dimensions. Increasing the sawbones density increased the bending strength and stiffness in all fixation groups except for constructs with a dorsal staple. Both the compressed and uncompressed beam resulted in significantly higher bending strength compared to staples in all configurations. Staples in the plantar orientation were significantly stronger than staples in the dorsal orientation. The addition of metal spacer did not significantly alter the bending mechanics, but can cause a slightly lower fracture strength if the size of the staple is not modified to span the larger gap caused by the spacer. The high throughput 4-point bending model is simple enough that the methods can be easily repeated to assess a wide range of fixation methods, while complex enough to provide clinically relevant information. It is recommended that this model is used to assess a large initial set of fixation methods in direct and straightforward comparisons. The results can narrow the list of potential fixation configurations that can be further assessed in subsequent cadaver studies. Aim 3 will seek to improve treatment for infected implants, the worst-case scenario, by developing an antibiotic eluting and loadbearing 3D printed spacer. This study focused on the treatments of periprosthetic joint infections, which are relatively rare complications of total joint replacements which has been becoming increasingly common. The standard of care involves the placement of a temporary spacer made out of polymethyl methacrylate (PMMA) bone cement combined with antibiotics. The rate of major complication can be as high as 12 % for PMMA spacers. Therefore, the purpose of this study was to develop a method to produce a biocompatible material that could be 3D printed, provide mechanical support needed for ambulation, and deliver a therapeutic dose of antibiotics. Printed structures were successfully fabricated out of biocompatible photoresin (BMC) doped with up to 16% gentamicin or 10 % vancomycin. PMMA and BMC composites were characterized with differential scanning calorimetry, dynamic mechanical analysis, wear testing, compression testing, and a 30-day drug elution study. The thermoset properties of the BMC allowed for the compressive properties to remain unchanged as antibiotics were added to the polymer, but limited the amount of drug that eluted out of the composite. In contrast, the thermoplastic properties of PMMA led to the compressive properties to decrease with the addition of antibiotics, but PMMA was able to elute significantly more antibiotics. In conclusion, this study described a novel method to 3D print a load bearing structures that can release antibiotics over 30 days. BMC composites have some advantages and disadvantages compared to PMMA that need to be considered when developing new treatments for orthopaedic infections.

3D printing is a promising new technology with the potential to create rapid, high-quality, durable custom implants that will provide physicians and patients with currently unattainable clinical solutions. However, it is falling short on its promise due to its inability achieve adequate mechanical properties compared to conventional manufacturing techniques. This work explores the structure and properties of 3D printed thermoplastics with relevant medical applications through fused filament fabrication (FFF) processing. Four FFF materials (PLA, PEEK, PEKK, and PPSU) are investigated with an emphasis on characterizing printed weld formation and the corresponding mechanical properties. Each material has properties that are suitable for varying applications, but a pervasive requirement for success is strong weld formation between printed layers. Weld formation and strength was tested through tensile testing of bulk samples with layers oriented perpendicular to loading direction and tear testing of individual welds. While PLA, PEEK, and PEKK derive strength from their crystalline structures, crystallinity that developed during printing decreased the strength of materials as it inhibited polymer diffusion across the weld and prevented strong bonds from forming. Increasing crystallinity of as-printed amorphous samples through annealing did not result in higher strength for PLA or PEEK, due to the inability to co-crystallize across the weld interface. However, annealing amorphous PEKK samples resulted in a 26-40% increase in strength. While PEKK achieved the highest strength of 105 MPa, PPSU, a completely amorphous material, was closest to achieving conventional processing properties with a strength of 61 MPa.

Synthetic cartilage implants have the potential to deeply transform the treatment of articular cartilage degeneration as well as the progression of osteoarthritis in load-bearing applications of various joints in the human body. To reduce patient morbidity and enhance range of motion, surgeons and material scientists alike are looking to synthetic alternatives re-establish articular cartilage function without introducing higher cost and health burdens. These implants are rigorously tested for their compressive and wear properties over longer timeframes, with the first instance of approved human use coming in the 1st metatarsophalangeal (MTP) joint with poly(vinyl alcohol) (PVA) being the predominant polymer in composition. Despite their promise of dissipating stress and providing smooth joint movement, these synthetic cartilage implants are not well-studied for their tensile fatigue properties which are extremely critical to in vivo performance and implant survival. As a synthetic substitute to match the properties of cartilage in human beings, hydrogels are extensively researched due to their potential biocompatibility. This research describes work dedicated to the advanced mechanical study of synthetic hydrogel systems for cartilage-based applications. The materials of interest are designed to have enhanced monotonic tensile properties for supplementary investigation via tensile fatigue testing. Superior mechanical behavior was achieved through the use of bio-friendly additives, freezing-thawing cyclic processing, and fiber reinforcement. Lastly, the long-term failure mechanisms through flaw development for these synthetic hydrogel systems and biological tissue will be explored.