Background: Extended Reality (XR) has demonstrated significant improvements in multiple surgical specialties by reducing operative times and enhancing surgical outcomes. Nevertheless, its usability for perforator visualization in deep inferior epigastric perforator (DIEP) breast reconstruction remains largely unexplored.

Objective: The primary aim of this study was to assess the usability and potential added value of XR in DIEP flap breast reconstruction to enhance the three-dimensional understanding of the deep inferior epigastric artery and its perforators. The secondary objective of this study was to determine if the weight of DIEP flaps can be accurately estimated through the virtual model required for XR visualization.

Methods: This multicenter pilot study involved plastic surgeons and patients undergoing DIEP flap breast reconstruction at three Dutch medical centers. Abdominal computed tomography angiography (CTA) images were used to create virtual 3D models. Surgeons utilized the HoloLens 2 (Microsoft Corporation) to compare intraoperative findings regarding perforator caliber, location within the flap, and the intramuscular course of perforators against CTA. Usability was assessed via the System Usability Scale (SUS). The SUS, perforator characteristics, and the added value of XR in addition to CTA for preoperative planning of DIEP flap breast reconstruction were scored using a 5-point Likert scale with a minimum score of 1 and a maximum score of 5. Furthermore, DIEP flap weight estimations were derived from the segmentations of the DIEP flap required for the virtual model and compared with a two-dimensional method for DIEP flap weight predictions extracted from literature.

Results: This study presents the preliminary results. Up until now, five patients and surgeons have been included. SUS scores were 66 for CTA and 70 for XR, meaning both visualization methods have ‘Good’ usability. XR scored slightly higher compared to CTA regarding perforator caliber with median scores of 3 for CTA and 4 for XR. Location within the flap yielded median scores of 4 for CTA and 5 for XR. The median score for the intramuscular course was 4 for both CTA and XR. The median scores for utilizing XR in addition to CTA for preoperative planning of DIEP flap breast reconstruction and recommending it to a colleague were both 4. DIEP flap weight prediction derived from the virtual model compared to true flap weight showed a mean difference of 333 grams and a mean percentage difference of 18.9%, whereas the two-dimensional method showed a mean difference of 937 grams and a mean percentage difference of 44.5%.

Conclusion: The preliminary results from this study indicate that XR technology, using the HoloLens 2, is a feasible and potentially advantageous tool for preoperative planning in DIEP flap breast reconstruction. The usability of XR was found to be comparable to CTA, with slightly better performance in visualizing perforator characteristics. The positive feedback from participating surgeons suggests that XR could enhance the understanding of the DIEA and its perforators, potentially improving surgical outcomes. Accurate prediction of DIEP flap weight based on the virtual model using the methodology employed in this study is currently not feasible.

Introduction
Osteoarthritis (OA) is a prevalent joint disease affecting 7% of the global population in 2020. Lower limb malalignment emerges as a significant contributor to OA, presenting as varus or valgus misalignment. This deviation induces unicompartmental pathology, leading to the wear and tear of the protective cartilage. Surgical interventions, including osteotomies, are essential in managing unicompartmental knee OA. During osteotomies, hinge fractures are a common complication. This paper focuses on optimizing open wedge osteotomies, specifically exploring complications in medial open wedge distal femoral osteotomy (DFO) using finite element models. And investigates the viability of the medial open wedge DFO compared to the lateral open wedge DFO.
Method
The research employed a systematic approach to investigate ways to avoid hinge fractures in Distal Femoral Osteotomy (DFO). Finite Element Modelling (FEM) served as the cornerstone of our methodology, providing a numerical solution. The process involved the creation of finite element models from CT scans through the subdivision of femoral geometry. The automated generation of these models was facilitated by a combination of 3-matic, Mimics, and Abaqus. Using Python scripting in these different programs, a workflow for model creation and parameter variation was created. The lateral open wedge DFO model, serving as the baseline, underwent systematic alterations to explorethe impact of hinge size, osteotomy gap angle, and other variables. The creation of finite element models involved several key steps, including geometry creation, mesh generation, addition of material properties, and the application of boundary and loading conditions. Material properties were assigned based on a simplified isotropic model derived from Hounsfield units. Extra attention was given to automate the process of model generation to ensure efficiency and reproducibility.
Results
Six distinct models were created with a comprehensive analysis of their attributes and shortcomings. The study finds that the medial open wedge DFO does not induce hinge tension. Comparative analyses in both opening and loading stages reveal nuanced stress and strain differences with the lateral open wedge DFO. No clear conclusion can be given as to the viability of the medial open wedge DFO compared to the lateral open wedge DFO. In-depth exploration indicates that smaller hinges are favourable for osteotomy gap opening, while larger hinges (10mm and above) contribute to stability during loading. Minimal impact on stress concentration is observed for osteotomy gap angle variations. The study explores the effectiveness of drill holes in stress relief, highlighting precision challenges.
Discussion
Acknowledging inherent limitations such as partial volume effects and assumptions about material properties. The study suggests promising avenues for future research. Recommendations for future research include in vivo experiments, exploration of XFEM and fracture mechanics, and further refinement of modelling techniques. This study provides nuanced insights into hinge fractures during open wedge DFO, guiding future research and bridging the gap between finite element modelling and
clinical realities.

Introduction
An innovative, patient-specific, hip implant was developed for canine patients suffering from developmental hip dysplasia. In a first cohort study, the post-operative positions of the implants deviated with an average of 5 mm when compared to the pre-operatively planned positions. A novel augmented reality (AR) based intra-operative navigation method (Holoma) was proposed to decrease implant positioning errors to a maximum of 3 mm. Holoma provides ArUco marker-based, mixed reality surgical navigation on the Hololens 2. The goal of this study was to quantify the error associated with each technical component in Holoma, to determine its navigational accuracies.

Methods
Holoma’s technical errors were quantified in a laboratory setting within a surgical operation room. The accuracy of ArUco marker localization and the amount of jittering (falsely detected marker movement) were tested by performing stationary and dynamic experiments. The precision of three image-to-patient registration methods (marker pose, point-to-point, point cloud) was determined by calculating the euclidean distance between multiple registration attempts. Lastly, implant navigation accuracy was quantified by positioning an implant on a precisely predetermined position and recording Holoma’s navigation instructions.

Results
Holoma’s ArUco marker localization accuracy had a median error of -0.97 mm (min; max: -2.04; -0.27) with a marker-to-camera distance of 60 cm, and median jittering was 0.65 mm (min; max: 0; 2.07). Median image-to-patient registration precision was 2.20 mm (min; max: 0.39; 6.00), 3.52 mm (0.21; 6.92), and 3.79 mm (0.55; 8.83), for marker pose, point-to-point, and point cloud registration, respectively. Lastly, implant navigation instructions showed median errors of 2 mm (min; max: 0; 7), 3 mm (0; 7), and 4 mm (0; 9) after marker pose, point-to-point, and point cloud registration, respectively.

Discussion and conclusion
The experiments suggest an accumulation of technical errors in Holoma’s navigation application. The accuracy and precision of the navigation software were determined to be inadequate to decrease patient specific hip implant placement errors, at the time of investigating. Future improvements within Holoma will determine its feasibility for accurate implant navigation. Other navigation techniques should be considered in the search for optimal implant positioning guidance.

Introduction
Augmented Reality (AR) and Mixed Reality (MR) can be used for surgical navigation to execute the pre-operative plan. HoloMA is a novel AR/MR application which can guide the user to place surgical instruments on the planned location within the patient. In this pilot study, the AR/MR-guidance of HoloMA was used to place personalized canine acetabular roof implants on the pre-planned location on the iliac bone.

Methods
Dedicated tools to perform the AR/MR patient registration and surgical guidance were developed. An in silico patient registration test was conducted to assess if the available bony surface during the acetabular roof surgery was suitable to perform the patient registration accurately. Pilot tests to place implants using the AR/MR-guidance of HoloMA were conducted on phantoms, a cadaver and in an in vivo dog patient. The translational and angulation error between the planned and the post-operative implant positions were determined. The aim was to achieve implant placement with a maximum translational error of 4.0 mm and a maximum angulation error of 5.0° relative to the pre-operative plan.

Results
The in silico patient registration test demonstrated a mean translational error of 0.94 ± 0.23 mm and a mean angulation error of 2.49 ± 0.34°. In the phantom tests, implants (n=6) were placed with a mean translational error of 1.94 ± 0.79 mm. The mean angulation errors in this test were: 2.87 ± 1.81° (transversal plane), 1.72 ± 1.64° (dorsal plane) and 3.10 ± 2.52° (sagittal plane). Two of the implants of the phantom test and both implants of the cadaveric test (n=2) were positioned with a translational error exceeding 4.0 mm and/or angulation error exceeding 5.0° from the planned positions. No implants were placed using AR/MR-guidance in the in vivo dog patient test.

Conclusion
The results of the in silico patient registration test hold promise for the use of AR/MR-guidance in positioning personalized acetabular roof implants. However, the moderate outcomes observed in the phantom and cadaveric test suggest the need for further testing and improvements before deploying this AR/MR technology in a clinical setting.

Background
Adolescent idiopathic scoliosis (AIS) with a Cobb angle larger than 45° is a spinal deformity that needs surgical treatment to stop progression and reduce pain. Spinal fusion is a surgical procedure where rods are attached to the spine through screws to diminish the Cobb angle.
Objective
The metal rods are pre-bent to correct the spinal deformity as much as possible. This rod shape is currently based on experience of the orthopedic surgeon. The aim of this thesis is to use Fi-nite element analysis (FEA) to predict a suitable rod shape for AIS patients that need to un-dergo surgery. 
Method
An FE model of an AIS spine was created based on high quality CT images. Rotation of ver-tebrae led to the optimal shape of the spine in the coronal plane. Vertebral bodies in this model were one by one rotated to a new position from top to bottom, to bring the spine to a new state and align it as much as possible to a normal physiological shape. However, alignment of the spine is an iterative process and rotation of every subsequent vertebra affects the shape of the entire spine. For each vertebral rotation, the reaction moments to maintain the new position is determined in the FE spine model. The acquired reaction moments are transferred to an FE rod model to provide the pre-bending of a rod that can bring the spine in its new state.
Results
The FE spine model was corrected to reduce the Cobb angle as much as possible. The highest stresses were found at the spinal apex. The reaction moments were transferred to a rod that became deformed in such a manner that straightened the spine model and corrected the Cobb angle to its pre-determined position with 33% reduction.
Discussion
This is an exploratory study that examines the possibility to predict ideal rod shapes pre-operatively to reduce surgical duration and improve the quality of the procedure. An accessory rod shape was accomplished but could not be validated due to lack of comparable studies. Improved FE spine models will lead to higher reliability of FE pre-bent rod models. This can be accomplished by, for example, inclusion of ligaments, muscles and other structures in the FE model and use of time-dependent material properties. The current model did not lead to a perfect aligned physiological spine and optimization algorithms should be developed in future models to further improve pre-bending of the rods.
Conclusion
Pre-operative prediction can improve the quality and reduce the time of spinal fusion. Im-provements to the FE spine- and rod model, such as automation, generalization, inclusion of more structures, and optimization algorithms will lead to optimal pre-bending of rods and bet-ter and quicker surgical outcome.

The incidence of osteoporotic vertebral compression fractures (VCFs) is rapidly increasing, necessitating the identification of the most appropriate treatment method. The well-established first and second generation surgical procedures are not capable of giving optimal outcomes. Moreover, my literature study has shown little to no improvements for four of the most prevailing third generation procedures. As a consequence, the med-tech company Amber Implants B.V. developed a new 3D-printed porous titanium implant that has the potential to resolve difficulties and drawbacks that were identified for all former procedures. Nonetheless, the performance of this implant has never been tested before. Thus, the aim of this study was to pre-clinically evaluate the biomechanical properties regarding the spinal deformities for this implant. For the quantification, the prevention of spinal deformities was subdivided into the anterior height restoration and the kyphotic angle correction. The pre-clinical evaluation was conducted on isolated vertebrae originating from three human cadaver specimens. First, the most abundant type of all osteoporotic VCFs, a wedge fracture, was generated on the vertebrae with 40% anterior height decrease. Thereafter, vertebral restoration was performed with the implants. Besides, vertebral restoration with the second generation surgical procedure, the Balloon Kyphoplasty procedure (BKP), was performed likewise to serve as a comparative. After vertebral restoration, half of the implant group and the total BKP group were tested in a cyclic loading test that mimicked the activity during the first week after surgical VCF repair, i.e. 10.000 cycles with loads ranging from 100N to 600N. The other half of the implant group was tested under higher loading conditions, i.e. 10.000 cycles with loads ranging from 100N to 1000N. At each test stage the spinal deformities, which were subdivided into the anterior height and the kyphotic angle, were evaluated from micro-CT (μCT) data. Eventually, the μCT scans were compared in order to quantify the implant's performance. The anterior height restoration after vertebral restoration with the implant was outstanding compared to the BKP procedure. Thereby, a statistical significance difference (p<0.05) was not only observed for the anterior height restoration, but also for the central and posterior height restorations, between the two surgical procedures. Additionally, the kyphotic angle correction of the implant procedure outperformed the outcomes observed for the BKP. Nonetheless, after cyclic loading various drawbacks for the implants were observed, resulting in substantial decreases in outcomes for the height restoration and the kyphotic angle correction. Regarding the height decrease, most was found in the trabecular bone inferior to the implant. Presumably, the plastic deformation was induced by high local stresses as a result of the minimal contact area between the implant and the trabecular bone. Complementary, the rotation of the implant was observed to effect the implant's performance. Ultimately, it was concluded that the implant in its current design could not compete with the BKP procedure, neither with the third generation surgical repair procedures for an osteoporotic VCF such as Vertebral Body Stenting (VBS) and SpineJack. Nevertheless, the outcomes after vertebral restoration were promising. Therefore, it was assumed that the implant has a decent chance of succeeding after implementing some adjustments on the implant's geometry and the corresponding surgical tools.

The management of large acetabular defects remains one of the most challenging aspects of revision total hip arthroplasties. Failure of frequently used acetabular reconstruction components are, among others, caused by the lack of biological fixation, a non-physiological stress distribution and stress-shielding. Attempting to diminish these drawbacks of current implants a new acetabular cup has been explored. The double layer of this new acetabular cup better fills the acetabular defect. According to Wolff’s law this should reduce stress shielding and stimulate bone ingrowth. Part one of this study explores the relationship between unit cell size of the titanium and mechanical properties for the body centred cubic unit cell. Three graded lattices using different unit cell sizes were designed and 3D-printed out of commercially pure titanium (Grade 1) using selective laser melting. An unconfined compression test with cylindrical samples as well as a confined compression test with hemispherical samples were performed to obtain mechanical properties. An additional finite element study was used to validate the confined compression test. Acetabular defects were made in five Sawbones hemipelves which served as the basis for the design of the ‘patient specific’ acetabular cups. Three triflange and two unflanged acetabular cups were designed and 3D-printed out of commercially pure titanium (Grade 1) using selective laser melting. Mechanical properties were obtained from the unconfined compression tests. All acetabular cups were inserted by two orthopaedic surgeons at the UMC Utrecht. Cyclic testing was performed up to 1000 cycles to assess femoral head penetration under load after insertion. Additional penetration of the femoral head was found to be between 0.1781 and 0.3793 mm. Future work is needed to prevent strut breakage upon insertion and more research is needed in the fatigue behaviour of these new cups and their biological effect on living bone tissue.

The synergy of hydrogel processing and 3D printing technologies has paved the way for the development of advanced tissue engineering scaffolds. Hydrogels constitute a promising class of materials for the creation of scaffolds due to their permeable environment, suitable for encapsulation, as well as their tunable chemical and mechanical properties [1]. 3D printing, on the other hand, has immersed as a novel manufacturing technology that allows the creation of three dimensional constructs with pre-determined architecture. Current advancements haveenabledalsotheprintingofbiomaterialsincorporatingcellsandsupporting components creating complex structures that can mimic living tissue characteristics with high accuracy [2]. Stereolithography and particularly, the Digital Light Processing (DLP) technology appears as one of the most auspicious printing techniques for the fast creation of mechanically stable hollow structures. However, the difficulty in developing hydrogel bioinks, which could be used for the fabrication of high resolution complicated architectures with structural integrity, remains a challenge. In the present study, efforts were focused on finding the components that could be used for the creation of an optimal bioink suitable for DLP printing. After deciding on the most promising components, the bioink’s optimization in terms of printing resolution was performed taking under consideration the fundamental principles of stereolithography. To achieve this goal, the working curves and all the key parameters, which define a photopolymer’s behavior were studied. After the optimization of the resolution, the prospective bioinks were characterized in terms of their crosslinking efficiency and mechanical properties. Consequently, complex porous scaffolds were fabricated from the selected bioinks and mechanically tested. Finally, the encapsulation of cells into the bioinks, as well as, the seeding method were performed for the creation of cell-laden scaffolds, which were also studied through the performance of cell viability and proliferation tests.

Context. In times where human kind is facing serious challenges due to global warming, scarcity of natural resources and inequality, to continue producing food, especially meat, as it is now done, does not seem sustainable. For people that want to continue enjoying their delicious piece of steak, the manner in which meat is sourced will need to be redesigned. One of the disruptive initiatives in this field is in vitro cultured meat. For the cultivation of muscle tissue, one needs cells, chemical factors and the appropriate biomaterials
that function as a scaffold. Meatable B.V. is a food-technology startup that is a pioneer in the cultivation of steak-like meat using induced pluripotent stem cells. Aims. The aim of the study is to optimise the extracellular matrix (i.e. scaffold) mimicry of natural biomaterials to serve as a scaffold for 3D skeletal muscle tissue engineering, using iPSCs. The supplementary aim of this study is to determine the feasibility of the optimised scaffold as a proof of concept for cultured meat. Methods. The proof of concept model (Model A) was created in collaboration with researchers from the Loughborough University who demonstrated a scalable model for 3D human skeletal muscle tissue engineering. Their strategy was to use a hard plastic mould to confine and provide initial support for the viscoelastic hydrogel (matrigel and rat tail collagen) encapsulated with cells (C2C12 myoblasts). For the optimisation of the extracellular matrix for iPSCs for the production of cultured meat, this model was copied and repeated with different edible scaffold alternatives. The best alternative biomaterial (Model B) was further optimised in large scale
tissue moulds and compared to the proof of concept model and meat. Lastly, Model C was created by seeding iPSCs in Model B. The qualitative and quantitative comparisons were based on different analytical parameters.
Results. The hydrogel scaffolds of both models A and B were highly comparable in terms of permeability, scaffold compaction by cell activity and cell alignment. The improved model (B) resulted in a higher cell proliferation as seen by cell development and cell density. The stiffness of model A was half the stiffness of Model B, and the stiffness of Model B was more comparable with the higher
stiffness of beef steak (factor 5 difference). Nevertheless, when the improved model was seeded with pre-differentiated iPSCs (Model C) instead of C2C12 myoblasts, the results were clearly less successful than the first models and were not comparable with beef steak. Conclusions. This research describes the successful improvements of an existing 3D in-vitro skeletal tissue engineering method, as prototype model for cultured meat, that was for the first time seeded with iPSCs. Model B should be set as the basis model to optimise for the culture of iPSCs. The bovine collagen model with C2C12s was not comparable to steak, but a longer culture period could result in more comparable tissue. The main reason for the limitations of Model C was the maturation of iPSCs, which could be improved in different ways. In addition, there remain certain requirements to be met for the hydrogel scaold, mainly connected with current developments for recombinant animal-free materials. It can still be concluded that the less successful Model C was a step in the right direction to becoming a feasible model for the culture of in vitro meat.

Introduction. To prevent burns from scar formation and contraction, the use of splinting therapy in the early phase of wound healing is considered as an effective non-surgical method. Splinting entails the application of a mechanical load in the opposite direction of the contractile force within the wound, based on the assumption that wound- or scar contraction will be prevented or reduced. However, clinical research provides conflicting evidence on its effectiveness and optimal treatment method. Therefore, the aim of this study was to design an in vitro model to investigate the mechanoresponsive cellular effects of stress on specifically Human Eschar Fibroblasts and their extracellular matrix, in order to confirm or disprove effects of burn splinting. Methods. The two major players of the burn wound model include (1) the fibroblasts, and (2) the novel extracellular matrix they produce. Outcome measures were chosen that directly relate to matrix organization, fibroblast functioning and matrix functioning. Three chronological sub-goals were defined to achieve the goal of designing a burn wound splinting model: (1) Formulating a suitable mechanical stress protocol; (2) Select a system that enables the selected mechanical stress of extensible substrates that facilitate the growth of fibroblasts and their derived extracellular matrix; (3) Create and optimize conditions to culture fibroblasts on an extensible substrate. To successfully reach these goals, the current literature on this subject was evaluated and comparative experiments were executed. Feasibility of the model was tested in a pilot study. Results. The MCB1 stretching apparatus was provided by Association of Dutch Burn Centre as a suitable device, which was modified to fulfill all predefined requirements. Human Eschar fibroblasts and dermal fibroblasts were cultured on custom made silicone culture wells. Cross-linked gelatin-A coating and vitamin C-supplemented culture medium were selected for optimal cell culturing results. A clinically relevant stretching regimen was chosen, given the paucity of available evidence in literature. A pilot study to test the feasibility of the model indicated that both dynamic and static stretching of eschar fibroblasts show a trend towards thicker, denser collagen matrices compared to unstretched conditions. These collagen fibers also showed a greater degree of alignment. However, no definitive conclusions can be drawn since sample size is limited. Conclusion. The model presented in this work constitutes a practical framework to test mechanotransducive processes in burn scars on a cellular and molecular level. A pilot study using this model showed excellent feasibility

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine that can be treated by wearing a correctional rigid brace. The goal of brace treatment is prevention of curve progression, and in some cases the curve even decreases. The current problem concerning treatment of AIS lays in the design decisions made during manufacturing of the brace. Correctional forces are applied through static pressure pads added to the inside of the brace. Evaluation of the correct positioning and size of these forces is done through radiographic imaging which allows limited feedback intervals as cumulative exposure to ionizing radiation increases the risk of cancer development. The design of scoliotic braces is currently suboptimal as the manufacturing remains an inefficient process. Moreover, it was hypothesized that the corrective forces show decreasing time dependant behaviour due to viscoelastic properties of the human body adapting to the load.
The objectives of this study were therefore to increase the effectiveness of brace treatment, by determination of the time dependant behaviour and accurate positioning and sizing of correctional forces.
A dynamic brace was developed containing pressure regulated cuffs creating a three-point-bending system on the spine. A healthy (non-scoliotic) test subject wore the brace with the goal of creating a spinal curvature. The cuffs were tested on stress relaxation behaviour, which was needed to determine if possible changes in pressure were due to viscoelasticity of the cuffs or the body. The tests showed that pressure stayed constant over time, which excludes viscoelasticity of the cuffs. Moreover, compression tests were executed on a cuff to determine the relationship between external loads and internal pressures.
Ultrasound (US) imaging was used to evaluate the effect of the three-point-bending system on the spine. The images showed a curvature, but the results varied too much to draw conclusions from, as this imaging technique works best for large scoliotic curves. BoneMRI has higher imaging accuracy and adds an extra dimension, however supine positioning decreases the spinal curvature. The boneMRI results show a subtle curvature after applying pressure. The cuffs lengthened the spine and caused mechanical torsion. After one hour the lengthening remained equal but the mechanical torsion decreased to its starting value. Lengthening of the spine could be useful in brace treatment to create more space between vertebrae and facilitate vertebral realignment.
This research served as a proof of concept which can be further developed by testing on a scoliotic patient with a moderate spinal curvature. This could result in a dynamic brace used as a method to enhance the positioning and sizing of pressure pads for a static brace, or the dynamic brace design needs adjustment to use it as a daily worn brace which keeps correctional forces constant by adjusting pressures automatically.

Background: Patients who suffer from acetabular bone defects are often subjected to a decreased mobility and a loss of independence. To treat these bone defects, standard hemispherical acetabular implants offer in most cases the solution. However, when these defects are large, a custom triflange acetabular implant is needed. Although this type of implant performs well in general, it also has some drawbacks. These include higher costs and a longer design- and development cycle, since every implant is custom-made to the patient. In addition, it is expected that the triflange implant causes more stress-shielding (loss in bone-mineral-density (BMD) due to insufficient loads) than the standard implant. However, the evidence for this last statement is quite weak, since studies on both cups use different parameters,materials and environments. Objective: The objective of this study is to determine if the custom triflange cup causes indeed more stress-shielding than the standard hemispherical cup. Furthermore, the goal is to find a solution for this and the other above-mentioned drawbacks of the custom triflange cup. Therefore, the goal is to study the potential of a deformable acetabular cup, which in theory should solve these issues of the triflange cup. Methods: First a statistical shape model (SSM) of the human pelvis was developed to find patterns in defects of the pelvis, which could eliminate the need for customization. Next, a Finite Element (FE) Model with a bone-remodelling algorithm was developed to determine the difference in stress-shielding between the standard and the triflange cup. Furthermore, a FE model of a deformable implant is developed which is pressed into multiple defected pelvises. Finally, a machine-algoirthm is trained to predict the optimal deformable cup parameters, based on the type of defects. Results: Several modes of deformation were found with the SSM, which were utilised in creating damaged pelvises for the Finite Element Model. Furthermore, it was found that the custom triflange cup decreases the BMD of the pelvis by 28.6% compared to pelvis without cup. With a deformable implant, this decrease can be reduced to 7.1%, which is in the similair range as the standard hemispherical cup. Finally, it was found that the machine-learning algorithm can successfully predict the optimal cup parameters, based on the type and size of defects.

Cartilage repair remains a major challenge and treatment of osteochondral defects generally results in inferior quality fibrous repair tissue. This study aims to elaborate on the work of Korthagen et al. who developed a thermoplastic polyurethane and polyetherketoneketone implant to treat osteochondral defects. Although promising results were found, Korthagen et al. encountered difficulties binding the neo-tissue to the elastomer part of the implant. The goal of this study is therefore to test potential solutions to improve cell binding properties of the elastomer in vitro, and to optimize the elastomers mechanical properties to mimic native articular cartilage. The newly produced elastomer showed encouraging cell binding properties with multiple cells types. In addition, 3D printing and punching holes in the elastomer part of the implant both have great potential in creating porosity to physically anchor the neo-tissue. The optimal diameter of vertically aligned punched holes was found to be 319 $\mu$m. Not only provides this diameter optimal circumstances for cartilage to grow into, it also optimizes anchoring potential. Besides that, 3D printing efforts were found to be promising in creating both excellent cell facilitating properties as well as mechanical properties mimicking that of native articular cartilage. Both punched and 3D printed elastomer samples were tested for toxicity and immune response. Both tests delivered excellent results and no sign of toxicity or adverse immune response was detected. These results combined with the excellent cell binding properties of the elastomer strengthens our confidence in favorable future in vivo outcomes.

Prosthetic failure due to implant-associated infections remains a big problem, despite the extensive use of implants and number of researches performed on this topic. A new problem arises with the development of additively manufactured complex orthopedic metal implants. In spite of the advantages that come with patient specific implants to cure the most critical orthopedic situations, these implants are inherent to infection susceptibility. Currently, no study has shown deposition on such complex implants, therefore this research aims to make the first steps towards an antibacterial coating deposited on additively manufactured complex implants to fight peri implant infections. This is facilitated by means of electrophoretic deposition. In order to develop homogeneous deposition of a chitosan/gelatin based coating loaded with vancomycin or gentamicin on titanium implants, a state-of-the-art setup was used, containing a cylindrical counter electrode surrounding the complex specimen. After parameter optimization, in vitro release behaviour, cell viability assays and antibacterial tests were performed, in order to investigate the biological behaviour of the coating. The release behaviour, which was dependent on coating degradation, showed a burst release after one day followed by sustained release up to day seven. Specimen including antibiotics showed antibacterial effect against S. Aureus. While all planktonic bacteria where eradicated, biofilm formation by adherent bacteria was significantly decreased, however not prevented. Cell viability assay showed bacterial adherence and growth, with an increased rate in the gentamicin samples, potentially caused by the high hydrophilicity of this drug. While an in vivo study is suggested to obtain more in-depth insights in the biological behaviour of the coating, this method is suggested to be a successful way to create a homogeneous coating against peri implant infections on complex implants, preventing peri implant infections, to reduce the change of patient specific implant revision.

BACKGROUND: Knee problems are the most common complaints of the lower extremity in the Netherlands. Osteoarthritis has the highest prevalence of all knee complaints. Knee osteoarthritis is likely to start at the patellofemoral joint and is associated with the aggravation of pain. Mechanical overloading is hypothesized to contribute to the development and progression of patellofemoral osteoarthritis (PFOA). Several studies have explored the mechanical loading pattern of the patellofemoral joint. Because different biomechanical models were used, vastly different estimations of the patellofemoral joint contact force (PFJCF) were concluded. This diversity prevents a clear understanding of the role of mechanical overloading in PFOA, since it is unknown how different biomechanical models affect the PFJCF estimation. OBJECTIVES: This study will explore how different biomechanical models of the patellofemoral joint affect the estimated PFJCF for common weight-bearing activities. METHODS: Ten healthy participants were included in this study. Common weight-bearing activities (walking, stair ascending, stair descending, sit-to-stand and stand-to-sit) were performed in the motion lab. Marker trajectory data and force plate data were collected. The data were input to biomechanical models used to estimate the quadriceps muscle force and subsequently the PFJCF. The quadriceps muscle force was estimated using the inverse dynamics and static optimization method. From there on, the PFJCF was estimated using three PFJCF to quadriceps muscle force ratios (P2QFRs), each based on a different patellofemoral joint model (i.e. van Eijden’s model, Yamaguchi’s model and Gill’s model). For each weight-bearing activity, the peak PFJCF was obtained and the magnitude of the difference among the biomechanical models was explored. RESULTS: The static optimization method resulted in a significantly higher peak PFJCF compared to the inverse dynamics method in walking (largest effect size was 0.10 BW). However, for stair descending, sit-to-stand and stand-to-sit, the inverse dynamics method resulted in a significantly higher peak PFJCF compared to the static optimization method (largest effect size was 0.45 BW, 1.17 BW, 1.25 BW, respectively). No significantly difference was found for stair ascending. For walking, Yamaguchi’s model resulted in a significantly higher peak PFJCF compared to van Eijden’s model and Gill’s model, and van Eijden’s model resulted in a significantly higher peak PFJCF compared to Gill’s model (largest effect size was 0.06 BW). For stair ascending, stair descending, sit-to-stand and stand-to-sit, Gill’s model resulted in a significantly higher peak PFJCF compared to van Eijden’s model and Yamaguchi’s model. For stair descending the van Eijden’s model resulted in a significantly higher peak PFJCF compared to Yamaguchi’s model. The largest effect size was 0.15 BW, 0.32 BW, 0.72 BW and 0.72 BW, for respectively stair ascending, stair descending, sit-to-stand and stand-to-sit. CONCLUSION: The choice of a biomechanical model has a critical effect on the estimation of the magnitude of the PFJCF. Its differences might reach half the clinical size effects when comparing control to symptomatic PF pain patients.

It has been observed that fractured bones which are stabilized with a titanium fracture fixation plate, once healed, often refracture at an edge of the plate. This is believed to be caused by stress concentrations in the bone that take place at the location of the edges of the plate. Various implant parameters are known to affect these concentrations of stress, but we further hypothesized that the material of the plate has the most significant influence in reducing these concentrations, here referred to as ‘peak stresses’. Moreover, it was reasoned, based on relevant literature, that minimizing the peak stresses was not the only criteria that should be considered for the design of an optimal implant, the effect of the Interfragmentary strain on the healing outcome in the early stages after implantation is also crucial for the success of the implant. Otherwise the bone will never heal in the first place.

Thus, by assuming that different regions of the plate have a different influence in the peak stresses, it was suggested that a stiffness graded plate could minimize the peak stresses while still allowing for an acceptable interfragmentary strain at the early stages of healing, through an optimization. In order to prove or disprove all the hypotheses mentioned above, a Finite Element model of a fracture fixation construct was developed. For the selection of many of the modelling assumptions, a literature study was carried out. For the selection of the contact properties to be used, a graphical comparison study was done. For choosing an appropriate mesh, a mesh study was implemented.

Using this Finite Element model, it was possible firstly to show that while the material properties of the plate do in fact appear to be very influential in reducing the peak stresses, the thickness seems to be even more influential. For the latter a parametric study was carried out using the Taguchi method. Secondly, it was shown that different regions of the fracture fixation plate do have a different influence in the peak stresses of the bone. The outer most sections of the plate seem to always be the most influential. Lastly, optimisations were carried out in three different ways and although they all reduced the peak stresses, the method thought to be the simplest, yielded the most useful results. This consisted of dividing the plate only into three sections and assigning one material to the outer sections and another to the inner section.

Knowledge of the influence of loading directions on trabecular bone remodeling in spine is of significant value in understanding the development of spine deformities and vertebral bone quality across different scales. Information on the constitution of a preferred trabecular orientation and mechanical properties of trabecular bone are important indicators in this respect. The current thesis aimed at exploring these aspects across multiple length scales in the spine. The thesis is divided in two parts. The influence of loadings less dominant than compression, i.e. shear, on the constitution of a preferred trabecular orientation in the spine on the macro-tissue level (>10 mm) was investigated in the first part (Part I). This influence was related to mechanical characteristics of trabecular structures on the micro-tissue scale (1-10 mm) in the second part (Part II). In Part I, primary trabecular orientations (PTOsmacro) near the superior and inferior vertebral endplates of L1 and L5 of 6 human spine cadavers were determined on the macro level using micro computed tomography imaging (voxel size = 120 m3), by calculating the dominant fabric principal vector. Their relative deviations to the axial compression vectors in the spines, quantified by the normals to the endplate (NEs), were determined afterwards. The average deviation between the PTOmacro and NEs was 6.24⁰ (±4.34⁰). The PTOsmacro did not show a preference towards the anterior or posterior direction relative to the NE. From the deviations, it was concluded that trabecular bone in the spine predominantly adapts to compression loads. However, secondary loading directions, such as shear, are of additional influence. In Part II, 13 small cubes (6.0x6.0 mm) from the volumes of interest in Part I were analysed on the micro level with regard to elasticity. Components, component ratios and primary elastic orientations (PEOmicro) of elasticity tensors, computed by the simulation of mechanical tests in finite element (FE) models, were calculated. PTOs of the cubes (PTOsmicro) were compared to the PEOsmicro and related to the PTOsmacro and NEs (Part I) qualitatively. Elasticity tensor components were within a reasonable range (approximately 1-250 MPa, excluding outliers) and no material symmetry was found, i.e. the structures were mechanically anisotropic. PTOsmicro deviated 13.90⁰ (±8.04⁰) with respect to the PEOsmicro on average. 10 out of 13 PEOsmicro had similar anterior or posterior tendencies as the PTOsmacro with respect to the NEs. 11 out of 13 PTOsmicro had similar anterior or posterior tendencies as PTOsmacro with respect to the NEs. Elastic properties of typical trabecular structures in the vertebral bodies were successfully determined. Due to a relatively low resolution, PEOsmicro deviated strongly with the PTOsmicro. Such deviations could function as indicators for bone quality in skeletal disease diagnostics using low resolution imaging. PTOsmicro and PEOsmicro agreed relatively well to the PTOsmacro on the macro-tissue level, in terms of anteriorly or posterior tendencies relative to axial loading in the spine. This outcome shows promise for multi-scalar biomechanical analysis of trabecular bone.

Osteogenesis imperfecta (OI), also known as brittle bone disease, affects 1 in 10.000 births. This disease is characterized by skeletal dysplasias, bone fragility and many secondary health issues. It is a heritable disorder affecting collagen type I, which is an essential protein in bone tissue. Post-translational overmodifications in collagen biosynthesis disturb the collagen packing and alter the mineralization process. This results in bone with poor structural parameters and inferior mechanical properties. In the current study, we have tested the hypothesis that the structural and mechanical properties in bone samples from OI patients are related to altered post-translational modifications in the collagen molecules.Hydroxylysine (Hyl) and the crosslinks hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) in bone samples from OI patients were measured with liquid chromatography. Bone quantity, in terms of volumetric bone mineral density (vBMD) and volumetric tissue mineral density (vTMD), was measured with micro-computed tomography. Hardness and Young’s moduli were derived from indentation experiments. Lysine was overhydroxylated in OI bone (p < 0.001), which led to increased HP values (p < 0.001) and higher HP/LP ratios (p = 0.013) compared to controls. OI tissue mineral density was more heterogeneously distributed, although average vTMD values were similar in both groups. The vBMD was significantly higher in controls compared to OI bone samples. Elevated Hyl levels were significantly related to decreased vBMD and vTMD in bone samples from OI patients. In both OI and control samples, an increase in LP crosslinks was associated with elevated vTMD values. Indentation with a spherical tip (r = 0.25mm) showed no altered mechanical properties in OI compared with controls. Unfortunately, we could not determine if impaired overmodifications in collagen are related to the poor mechanical properties of OI bone. Young’s moduli and hardness were not related to HP levels or HP/LP ratios. In control bone samples a negative correlation between Hyl residues and mechanical properties is observed. More mechanical experiments are necessary to address the hypothesis appropriately.

Massive acetabular bone defects are difficult to treat with the currently available implants. Advances in additive manufacturing create new design possibilities, which allow the production of patient specific implants. These endless possibilities will enable to tune the mechanical properties of porous implants and to distribute the loads in such a way that it mimics the natural load distribution. This technique will therefore be used in the design of a new type of implant, which is a deformable acetabular implant that will fully fit in a massive acetabular defect after plastic deformation. In this way, all remaining bone will be loaded, and the physiological load distribution will be restored to maximally reduce stress shielding and to prevent further loss of bone stock. To design this new implant, more information is required on the mechanical properties of the titanium porous structures. Therefore, the aim of this study is to examine the mechanical properties and deformation behaviour of highly porous pure titanium (grade 1) structures. The diamond unit cell was used to design three types of structures with different porosities (> 95%). A static compression test was performed on cylindrical samples. In addition, push-in and pull-out tests were performed on hemispherical shaped samples. The samples were compressed into specially designed moulds, which represent the acetabulum with defects, to test how these structures deform according to their surrounding shape. Micro-CT images were made during and after the test to analyse the deformation. The cylindrical samples continuously deformed during compression and large plastic strains were measured (> 57%). The hemispherical samples deformed conform the surrounding mould and even penetrated into the holes. The push-in and pull-out forces are positively correlated, and these forces are lower for more porous structures. The micro-CT scans show that all unit cells within the structure do not equally deform under compression, but show a gradual, layer-by-layer deformation. This study is a first step towards the design of a deformable implant. The results are quite promising and can function as a basis for future work.