Finite element analysis of patient-specific additive-manufactured implants.

Introduction: Bone tumors, characterized by diverse locations and shapes, often necessitate surgical excision followed by custom implant placement to facilitate targeted bone reconstruction. Leveraging additive manufacturing, patient-specific implants can be precisely tailored with complex geometries and desired stiffness, enhancing their suitability for bone ingrowth. Methods: In this work, a finite element model is employed to assess patient-specific lattice implants in femur bones. Our model is validated using experimental data obtained from an animal study (n = 9). Results: The results demonstrate the accuracy of the proposed finite element model in predicting the implant mechanical behavior. The model was used to investigate the influence of reducing the elastic modulus of a solid Ti6Al4V implant by tenfold, revealing that such a reduction had no significant impact on bone behavior under maximum compression and torsion loading. This finding suggests a potential avenue for reducing the endoprosthesis modulus without compromising bone integrity. Discussion: Our research suggests that employing fully lattice implants not only facilitates bone ingrowth but also has the potential to reduce overall implant stiffness. This reduction is crucial in preventing significant bone remodeling associated with stress shielding, a challenge often associated with the high stiffness of fully solid implants. The study highlights the mechanical benefits of utilizing lattice structures in implant design for enhanced patient outcomes.

Reducing the prosthesis modulus by inclusion of an open space lattice improves osteogenic response in a sheep model of extraarticular defect.

Introduction: Stress shielding is a common complication following endoprosthetic reconstruction surgery. The resulting periprosthetic osteopenia often manifests as catastrophic fractures and can significantly limit future treatment options. It has been long known that bone plates with lower elastic moduli are key to reducing the risk of stress shielding in orthopedics. Inclusion of open space lattices in metal endoprostheses is believed to reduce the prosthesis modulus potentially improving stress shielding. However, no in vivo data is currently available to support this assumption in long bone reconstruction. This manuscript aims to address this hypothesis using a sheep model of extraarticular bone defect. Methods: Initially, CT was used to create a virtual resection plan of the distal femoral metaphyses and to custom design endoprostheses specific to each femur. The endoprostheses comprised additively manufactured Ti6Al4V-ELI modules that either had a solid core with a modulus of ∼120 GPa (solid implant group) or an open space lattice core with unit cells that had a modulus of 3-6 GPa (lattice implant group). Osteotomies were performed using computer-assisted navigation followed by implantations. The periprosthetic, interfacial and interstitial regions of interest were evaluated by a combination of micro-CT, back-scattered scanning electron microscopy (BSEM), as well as epifluorescence and brightfield microscopy. Results: In the periprosthetic region, mean pixel intensity (a proxy for tissue mineral density in BSEM) in the caudal cortex was found to be higher in the lattice implant group. This was complemented by BSEM derived porosity being lower in the lattice implant group in both caudal and cranial cortices. In the interfacial and interstitial regions, most pronounced differences were observed in the axial interfacial perimeter where the solid implant group had greater bone coverage. In contrast, the lattice group had a greater coverage in the cranial interfacial region. Conclusion: Our findings suggest that reducing the prosthesis modulus by inclusion of an open-space lattice in its design has a positive effect on bone material and morphological parameters particularly within the periprosthetic regions. Improved mechanics appears to also have a measurable effect on the interfacial osteogenic response and osteointegration.

Robot-assisted implantation of additively manufactured patient-specific orthopaedic implants: evaluation in a sheep model.

PURPOSE: Bone tumours must be surgically excised in one piece with a margin of healthy tissue. The unique nature of each bone tumour case is well suited to the use of patient-specific implants, with additive manufacturing allowing production of highly complex geometries. This work represents the first assessment of the combination of surgical robotics and patient-specific additively manufactured implants. METHODS: The development and evaluation of a robotic system for bone tumour excision, capable of milling complex osteotomy paths, is described. The developed system was evaluated as part of an animal trial on 24 adult male sheep, in which robotic bone excision of the distal femur was followed by placement of patient-specific implants with operative time evaluated. Assessment of implant placement accuracy was completed based on post-operative CT scans. RESULTS: A mean overall implant position error of 1.05 ± 0.53 mm was achieved, in combination with a mean orientation error of 2.38 ± 0.98°. A mean procedure time (from access to implantation, excluding opening and closing) of 89.3 ± 25.25 min was observed, with recorded surgical time between 58 and 133 min, with this approximately evenly divided between robotic (43.9 ± 15.32) and implant-based (45.4 ± 18.97) tasks. CONCLUSIONS: This work demonstrates the ability for robotics to achieve repeatable and precise removal of complex bone volumes of the type that would allow en bloc removal of a bone tumour. These robotically created volumes can be precisely filled with additively manufactured patient-specific implants, with minimal gap between cut surface and implant interface.

Molecular Dynamics Simulations and Experimental Results Provide Insight into Clinical Performance Differences between Sandimmune® and Neoral® Lipid-Based Formulations.

OBJECTIVE: Molecular dynamics (MD) simulations provide an in silico method to study the structure of lipid-based formulations (LBFs) and the incorporation of poorly water-soluble drugs within such formulations. In order to validate the ability of MD to effectively model the properties of LBFs, this work investigates the well-known cyclosporine A formulations, Sandimmune® and Neoral®. Sandimmune® exhibits poor dispersibility and its absorption from the gastrointestinal tract is enhanced when administered after food, whereas Neoral® disperses comparatively well and shows no food effect. METHODS: MD simulations were performed of both LBFs to investigate the differences observed in fasted and fed conditions. These conditions were also tested using an in vitro experimental model of dispersion and digestion. RESULTS: These MD simulations were able to show that the food effect observed for Sandimmune® can be explained by large changes in drug solubilization on addition of bile. In contrast, Neoral® is well dispersed in water or in simulated fasted conditions, and this dispersion is relatively unchanged on moving to fed conditions. These differences were confirmed using dispersion and digestion in vitro experimental model. CONCLUSIONS: The current data suggests that MD simulations are a potential method to model the fate of LBFs in the gastrointestinal tract, predict their dispersion and digestion, investigate behaviour of APIs within the formulations, and provide insights into the clinical performance of LBFs.