Optimizing the Surgical Treatment of Large Orthopaedic Injuries

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.