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

After en bloc resection of primary pelvic bone tumours, orthopaedic oncologists usually try to perform reconstruction in order to achieve limb salvage. Reconstruction after these types of resections is challenging. Especially when the total ilium and parts of the sacrum needs to be removed. One of the reconstructive options is endoprosthetic fixation to sacral bone with the LUMiC prosthesis, but using the LUMiC prosthesis in the sacrum resulted in poor clinical results. Emerging new production techniques such as 3D printing provide for customised prostheses that could be an adequate reconstructive option in these cases and could complement the LUMiC prosthesis to enable sacral anchoring of the LUMiC prosthesis. One of the challenges of customised prostheses is that they are not ‘off the shelf’ and therefore are all different in terms of geometry and, thus, performance. Therefore, these implants cannot be subjected to stringent regulations and registrations used in conventional arthroplasty. In order to ensure maximal safety of these implants we must perform biomechanical testing before implantation. Unfortunately, the bone models for biomechanical testing currently available are not validated on implant fixation and thus unreliable for prosthesis testing. Therefore, in this thesis a new prosthesis that enables sacral anchoring of the cup of the LUMiC prosthesis is designed and two strategies are developed in order to mechanically evaluate this newly designed prosthesis for the sacral anchoring of the LUMiC cup. First strategy is using Finite element modelling to develop a model of the sacrum with implanted prosthesis. Second strategy is the development of 3D bone models of the sacrum using 3D printing together with performing experiments to mechanically evaluate the newly designed prosthesis. Four different mechanical bone models with different shell thickness and infill density were developed and compared to the FE model. Results showed that the new prosthesis design performed better in terms of micromotions between implant and bone compared to the use of the old LUMiC stem in the FE model. Furthermore, a 3D printed mechanical bone model with shell thickness of 1mm and infill structure of 20% showed most comparable results in terms of micromotions between implant and bone compared to the developed FE model. There could be concluded that the FE model and the development of 3D printed mechanical bone models together with the experiments are good starting points in the development of a protocol to in vitro evaluate newly designed 3D printed patient specific prosthesis for the sacrum after tumour resection. The mechanical bone model with shell thickness 1mm and infill structure 20% is the best option in terms of mimicking real bone. Furthermore, the newly designed prosthesis for sacral anchoring of the LUMiC cup showed promising results and could be considered as a improved alternative for the old LUMiC prosthesis stem. In future research cadaver tests should be performed to further validate the found results.

Bone defects are a common problem in healthcare today. When the damage is too extensive, the human body is not able to heal itself. Different solutions are available, but they all have limitations. Therefore, the search for a solution to overcome these limitations is important. In this theses a way to create a scaffold out of seperate crumpled elements is explored. Mechanical and morphological properties are examined.

With the aging population growing, the increasing prevalence of osteoarthritis (OA) seems inevitable. As a result, the number of joint replacements is expected to grow substantially within the next decade. Today’s hip replacements have the potential to function for more than 20 years, but due to risk factors such as aseptic loosening, the younger patients will most certainly outlive their prostheses. Aseptic loosening refers to the mechanical failure of the implant-bone interface, which may arise as the end result of stress shielding or improper design. In places where the bone is understressed for prolonged periods of time, bone resorption will set in, which can eventually lead to implant failure. Optimization of this bone-implant interface is therefore of utter importance to increase the implant’s longevity. Recent advances in additive manufacturing (AM) have enabled the fabrication of highly-complex micro-architectures, which can be designed to exhibit novel mechanical properties at the macroscale. The development of these mechanical metamaterials has paved the way for personalized, life-lasting implants. This explorative study aimed to investigate the mechanical properties of 3D AM (hybrid) mechanical metamaterials and their potential to improve the mechanical fixation of off-axially loaded AM meta-implants, using the mechanical responsiveness of bone. The mechanical properties of six different 3D AM mechanical metamaterials were assessed during axial compression, with the help of Digital Image Correlation (DIC). Combinations of mechanical metamaterials were made to obtain novel 3D hybrid mechanical metamaterials, for which the expansions and initiated strain distributions were determined using DIC, upon off-axial compression. Finally, five different meta-implants (femoral stems) were designed. A compression was applied at the femoral head to examine the strain distributions in the surrounding, bone-mimicking foam blocks. Hybrid meta-implant Type 2 showed the most continuous compressive strain distribution, with a considerably different lateral strain profile compared to the current generation of femoral stems. These studies therefore demonstrate the potential of applying hybrid mechanical metamaterials in off-axially loaded meta-implants, such as the femoral stem, to initiate bilateral strains and potentially stimulate osseointegration at the bone-implant interface.