In silico medical device testing of anatomically and mechanically conforming patient-specific spinal fusion cages designed by full-scale topology optimisation.

A full-scale topology optimisation formulation has been developed to automate the design of cages used in instrumented transforaminal lumbar interbody fusion. The method incorporates the mechanical response of the adjacent bone structures in the optimisation process, yielding patient-specific spinal fusion cages that both anatomically and mechanically conform to the patient, effectively mitigating subsidence risk compared to generic, off-the-shelf cages and patient-specific devices. In this study, in silico medical device testing on a cohort of seven patients was performed to investigate the effectiveness of the anatomically and mechanically conforming devices using titanium and PEEK implant materials. A median reduction in the subsidence risk by 89% for titanium and 94% for PEEK implant materials was demonstrated compared to an off-the-shelf implant. A median reduction of 75% was achieved for a PEEK implant material compared to an anatomically conforming implant. A credibility assessment of the computational model used to predict the subsidence risk was provided according to the ASME V&V40-2018 standard.

Anatomically and mechanically conforming patient-specific spinal fusion cages designed by full-scale topology optimization.

Cage subsidence after instrumented lumbar spinal fusion surgery remains a significant cause of treatment failure, specifically for posterior or transforaminal lumbar interbody fusion. Recent advancements in computational techniques and additive manufacturing, have enabled the development of patient-specific implants and implant optimization to specific functional targets. This study aimed to introduce a novel full-scale topology optimization formulation that takes the structural response of the adjacent bone structures into account in the optimization process. The formulation includes maximum and minimum principal strain constraints that lower strain concentrations in the adjacent vertebrae. This optimization approach resulted in anatomically and mechanically conforming spinal fusion cages. Subsidence risk was quantified in a commercial finite element solver for off-the-shelf, anatomically conforming and the optimized cages, in two representative patients. We demonstrated that the anatomically and mechanically conforming cages reduced subsidence risk by 91% compared to an off-the-shelf implant with the same footprint for a patient with normal bone quality and 54% for a patient with osteopenia. Prototypes of the optimized cage were additively manufactured and mechanically tested to evaluate the manufacturability and integrity of the design and to validate the finite element model.

3D-printed LEGO®-inspired titanium scaffolds for patient-specific regenerative medicine.

Despite the recent advances in 3D-printing, it is often difficult to fabricate implants that optimally fit a defect size or shape. There are some approaches to resolve this issue, such as patient-specific implant/scaffold designs based on CT images of the patients, however, this process is labor-intensive and costly. Especially in developing countries, affordable treatment options are required, while still not excluding these patient groups from potential material and manufacturing advances. Here, a selective laser melting (SLM) 3D-printing strategy was used to fabricate a hierarchical, LEGO®-inspired Assemblable Titanium Scaffold (ATS) system, which can be manually assembled in any shape or size with ease. A surgeon can quickly create a scaffold that would fit to the defect right before the implantation during the surgery. Additionally, the direct inclusion of micro- and macroporous structures via 3D-printing, as well as a double acid-etched surface treatment (ST) in the ATS, ensure biocompatibility, sufficient nutrient flow, cell migration and enhanced osteogenesis. Three different structures were designed (non-porous:NP, semi-porous:SP, ultra-porous:UP), 3D-printed with the SLM technique and then surface treated for the ST groups. After analyzing characteristics of the ATS such as printing quality, surface roughness and interconnected porosity, mechanical testing and finite element analysis (FEA) demonstrated that individual and stacked ATS have sufficient mechanical properties to withstand loading in a physiological system. All ATS showed high cell viability, and the SP and UP groups demonstrated enhanced cell proliferation rates compared to the NP group. Furthermore, we also verified that cells were well-attached and spread on the porous structures and successful cell migration between the ATS units was seen in the case of assemblies. The UP and SP groups exhibited higher calcium deposition and RT-qPCR proved higher osteogenic gene expression compared to NP group. Finally, we demonstrate a number of possible medical applications that reveal the potential of the ATS through assembly.

A 3D-Printed Assemblable Bespoke Scaffold as a Versatile Microcryogel Carrier for Site-Specific Regenerative Medicine.

Advances in additive manufacturing have led to diverse patient-specific implant designs utilizing computed tomography, but this requires intensive work and financial implications. Here, Digital Light Processing is used to fabricate a hive-structured assemblable bespoke scaffold (HIVE). HIVE can be manually assembled in any shape/size with ease, so a surgeon can create a scaffold that will best fit a defect before implantation. Simultaneously, it can have site-specific treatments by working as a carrier filled with microcryogels (MC) incorporating different biological factors in different pockets of HIVE. After characterization, possible site-specific applications are investigated by utilizing HIVE as a versatile carrier with incorporated treatments such as growth factors (GF), bioceramic, or cells. HIVE as a GF-carrier shows a controlled release of bone morphogenetic protein/vascular endothelial growth factor (BMP/VEGF) and induced osteogenesis/angiogenesis from human mesenchymal stem cells (hMSC)/human umbilical vein endothelial cells (HUVECs). Furthermore, as a bioceramic-carrier, HIVE demonstrates enhanced mineralization and osteogenesis, and as a HUVEC carrier, it upregulates both osteogenic and angiogenic gene expression of hMSCs. HIVE with different combinations of MCs yields a distinct local effect and successful cell migration is confirmed within assembled HIVEs. Finally, an in vivo rat subcutaneous implantation demonstrates site-specific osteogenesis and angiogenesis.

Conceptual design of compliant bone scaffolds by full-scale topology optimization.

A promising new treatment for large and complex bone defects is to implant specifically designed and additively manufactured synthetic bone scaffolds. Optimizing the scaffold design can potentially improve bone in-growth and prevent under- and over-loading of the adjacent tissue. This study aims to optimize synthetic bone scaffolds over multiple-length scales using the full-scale topology optimization approach, and to assess the effectiveness of this approach as an alternative to the currently used mono- and multi-scale optimization approaches for orthopaedic applications. We present a topology optimization formulation, which is matching the scaffold's mechanical properties to the surrounding tissue in compression. The scaffold's porous structure is tuneable to achieve the desired morphological properties to enhance bone in-growth. The proposed approach is demonstrated in-silico, using PEEK, cortical bone and titanium material properties in a 2D parameter study and on 3D designs. Full-scale topology optimization indicates a design improvement of 81% compared to the multi-scale approach. Furthermore, 3D designs for PEEK and titanium are additively manufactured to test the applicability of the method. With further development, the full-scale topology optimization approach is anticipated to offer a more effective alternative for optimizing orthopaedic structures compared to the currently used multi-scale methods.