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Item type:Publication, Access status: without files , Evaluation of angiogenic potential of silk fibroin fleece and membrane scaffolds using a co-culture system of huvecs and dpscs in fibrin gel(Elsevier, 2026-09-10); ; ; Gosau, MartinPublicationtype: Journal Article6 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Local mechanical stresses can explain the mechanoregulation of bone healing after mandibular reconstruction: an in silico studyObjectives: Recent advancements in mandibular reconstruction, including virtual surgical planning and patient-specific 3D-printed reconstruction plates, have improved surgical precision but have not yet fully optimized the mechanical environment for bone healing. This study aimed to investigate the level of mechanical signals that may promote bone regeneration in mandibular reconstruction with patient-specific plates. Materials and methods: A coupled finite‑element and agent‑based mechanobiological model for mandibular bone healing was developed to predict bone formation after mandibular reconstruction. A finite element model (FEM) of a monosegmental mandibular reconstruction with a patient-specific 3D-printed plate during unilateral clenching was coupled with a 3D agent-based model to simulate cellular activities at the osteotomy sites. Using an established mechano-regulation theory, tissue formation and resorption were simulated based on mechanical signals. The latter were systematically varied to identify thresholds matching clinical observations. Results: Increasing the ossification threshold from 0.15 MPa to 0.30 MPa improved agreement with clinical data, leading to 39% and 69% of bone formation in the anterior and posterior gaps, respectively, after 90 days. Conclusions: The model was able to predict levels of newly-formed bone as per clinical observations. Adaptation of the mechano-regulation theory to the mandibular environment suggested that mandibular bone regeneration might occur at a higher level of mechanical stress than in long bones. Clinical relevance: This study presented a computational framework that could, in the future, be incorporated into the clinical workflow during virtual surgical planning to support the mechanical optimization of patient-specific fixation devices and ultimately enhance the healing outcome.Publicationtype: Journal Article15 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Computer-aided scaffold design optimization towards enhanced bone regenerationLarge bone defects remain a clinical challenge, with a gold standard treatment - autologous bone graft - that presents many drawbacks. Design optimized scaffolds appear as a promising alternative [1]; however, bone scaffold design remains a trial and error approach where some specific properties (porosity, mechanical properties, etc) are individually optimized. Thus, the aim of this study was to develop a computer-aided scaffold design optimisation framework towards enhanced bone regeneration, taking into account the dynamics of the bone regeneration process. A computer model of scaffold-guided bone regeneration was developed and tested against different experimental setups that have used different scaffold designs for large bone defect healing in large animal models [2,3]. The model takes into account the scaffold design (architecture and material properties) as well as its interaction with different cellular processes (e.g. migration). Computer model predictions of bone tissue formation within the scaffold pores were compared against in vivo experimental data. The validated model was then used to develop a computer framework that allow us to optimize the scaffold design with the objective of achieving maximum bone regeneration. The computer model of scaffold-supported bone regeneration is able to explain experimental observations of bone tissue formation within a honeycomb titanium scaffold and a strut-based PCL-βTCP scaffold. In both experimental settings, scaffold surface guidance was predicted to play a key role on the regulation of cellular activity. Computer-aided optimization resulted in a scaffold design which was predicted to achieve almost complete bone regeneration within a large bone defect. We have developed a framework that allows 1) to investigate the mechanisms behind scaffold-supported bone regeneration and 2) to optimize the scaffold design to achieve maximum bone regeneration. Although, the computer model of bone regeneration has shown promising results in different experimental settings, further testing of the model and validation against experimental data is needed to ensure model robustness. The optimization framework allows shape optimization of specific scaffold designs. Future studies will focus on the validation of the optimization framework.Publicationtype: Conference Paper24 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Spatial variations in the osteocyte lacunocanalicular network density and analysis of the connectomic parametersOsteocyte lacuno-canalicular network (LCN) is comprised of micrometre-sized pores and submicrometric wide channels in bone. Accumulating evidence suggests multiple functions of this network in material transportation, mechanobiological signalling, mineral homeostasis and bone remodelling. Combining rhodamine staining and confocal laser scanning microscopy, the longitudinal cross-sections of six mouse tibiae were imaged, and the connectome of the network was quantified with a focus on the spatial heterogeneities of network density, connectivity and length of canaliculi. In-vivo loading and double calcein labelling on these tibiae allowed differentiating the newly formed bone from the pre-existing regions. The canalicular density of the murine cortical bone varied between 0.174 and 0.243 μm/μm3, and therefore is three times larger than the corresponding value for human femoral midshaft osteons. The spatial heterogeneity of the network was found distinctly more pronounced across the cortex than along the cortex. We found that in regions with a dense network, the LCN conserves its largely tree-like character, but increases the density by including shorter canaliculi. The current study on healthy mice should serve as a motivating starting point to study the connectome of genetically modified mice, including models of bone diseases and of reduced mechanoresponse.Publicationtype: Journal Article11 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Computational design and evaluation of the mechanical and electrical behavior of a piezoelectric scaffold : a preclinical study(Frontiers Media S.A., 2024-01-11); ; ; ; Piezoelectric scaffolds have been recently developed to explore their potential to enhance the bone regeneration process using the concept of piezoelectricity, which also inherently occurs in bone. In addition to providing mechanical support during bone healing, with a suitable design, they are supposed to produce electrical signals that ought to favor the cell responses. In this study, using finite element analysis (FEA), a piezoelectric scaffold was designed with the aim of providing favorable ranges of mechanical and electrical signals when implanted in a large bone defect in a large animal model, so that it could inform future pre-clinical studies. A parametric analysis was then performed to evaluate the effect of the scaffold design parameters with regard to the piezoelectric behavior of the scaffold. The designed scaffold consisted of a porous strut-like structure with piezoelectric patches covering its free surfaces within the scaffold pores. The results showed that titanium or PCL for the scaffold and barium titanate (BT) for the piezoelectric patches are a promising material combination to generate favorable ranges of voltage, as reported in experimental studies. Furthermore, the analysis of variance showed the thickness of the piezoelectric patches to be the most influential geometrical parameter on the generation of electrical signals in the scaffold. This study shows the potential of computer tools for the optimization of scaffold designs and suggests that patches of piezoelectric material, attached to the scaffold surfaces, can deliver favorable ranges of electrical stimuli to the cells that might promote bone regeneration.Publicationtype: Journal Article7 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Comparative study of CAD/CAM reconstruction and miniplates for patient-specific fixation in LCL-type mandibular reconstruction(2024); ; ; Objective: Miniplates offer superior clinical handling and facilitate postoperative removal after mandibular reconstruction but unfavorable load distribution under high stress has been shown. This study aimed to compare the clinical outcome of patient-specific 3D-printed (PS-3D) titanium miniplate with reconstruction plate fixation in three-segmental LCL-type reconstructions for the first time. Methods: Patients undergoing three-segmental LCL-type mandibular reconstruction after malignant tumor resection between April 2017 and July 2023 were analyzed in a retrospective single-center study. Inclusion criteria were primary reconstruction using a fibula free flap and PS-3D titanium mini- or reconstruction plate fixation. Complication rates were recorded and analyzed within 6 months after surgery using the N – 1 Chi2- and unequal variance t-test. Results: 38 patients (10 females, 28 males; mean age 61.4 ± 7.6 years) met the inclusion criteria. In 14 patients (36.8%) miniplates were used in the anterior region. Rates of fixation failure, plate exposure, incomplete osseous union, wound infection, soft tissue, and overall complications did not differ significantly between the two plate systems. Conclusion: Complication rates did not differ significantly between PS-3D mini- and reconstruction plates in three-segmental LCL-type mandibular reconstructions. Given their advantages in clinical handling and postoperative removal, PS-3D miniplates can be a viable alternative also in larger mandibular reconstructions.Publicationtype: Journal Article13 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Biomechanical evaluation of CAD/CAM magnesium miniplates as a fixation strategy for the treatment of segmental mandibular reconstruction with a fibula free flapTitanium patient-specific (CAD/CAM) plates are frequently used in mandibular reconstruction. However, titanium is a very stiff, non-degradable material which also induces artifacts in the imaging. Although magnesium has been proposed as a potential material alternative, the biomechanical conditions in the reconstructed mandible under magnesium CAD/CAM plate fixation are unknown. This study aimed to evaluate the primary fixation stability and potential of magnesium CAD/CAM miniplates. The biomechanical environment in a one segmental mandibular reconstruction with fibula free flap induced by a combination of a short posterior titanium CAD/CAM reconstruction plate and two anterior CAD/CAM miniplates of titanium and/or magnesium was evaluated, using computer modeling approaches. Output parameters were the strains in the healing regions and the stresses in the plates. Mechanical strains increased locally under magnesium fixation. Two plate-protective constellations for magnesium plates were identified: (1) pairing one magnesium miniplate with a parallel titanium miniplate and (2) pairing anterior magnesium miniplates with a posterior titanium reconstruction plate. Due to their degradability and reduced stiffness in comparison to titanium, magnesium plates could be beneficial for bone healing. Magnesium miniplates can be paired with titanium plates to ensure a non-occurrence of plate failure.Publicationtype: Journal Article12 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Reduced bone regeneration in rats with type 2 Diabetes Mellitus as a result of impaired stromal cell and osteoblast function : a computer modeling study(Wiley, 2023-11-01); ; ; Bone has the fascinating ability to self-regenerate. However, under certain conditions, such as type 2 diabetes mellitus (T2DM), this ability is impaired. T2DM is a chronic metabolic disease known by the presence of elevated blood glucose levels that is associated with reduced bone regeneration capability, high fracture risk, and eventual non-union risk after a fracture. Several mechanical and biological factors relevant to bone regeneration have been shown to be affected in a diabetic environment. However, whether impaired bone regeneration in T2DM can be explained due to mechanical or biological alterations remains unknown. To elucidate the relevance of either one, the aim of this study was to investigate the relative contribution of T2DM-related alterations on either cellular activity or mechanical stimuli driving bone regeneration. A previously validated in silico computer modeling approach that was capable of explaining bone regeneration in uneventful conditions of healing was further developed to investigate bone regeneration in T2DM. Aspects analyzed included the presence of mesenchymal stromal cells (MSCs), cellular migration, proliferation, differentiation, apoptosis, and cellular mechanosensitivity. To further verify the computer model findings against in vivo data, an experimental setup was replicated, in which regeneration was compared in healthy and diabetic after a rat femur bone osteotomy stabilized with plate fixation. We found that mechanical alterations had little effect on the reduced bone regeneration in T2DM and that alterations in MSC proliferation, MSC migration, and osteoblast differentiation had the highest effect. In silico predictions of regenerated bone in T2DM matched qualitatively and quantitatively those from ex vivo μCT at 12 weeks post-surgery when reduced cellular activities reported in previous in vitro and in vivo studies were included in the model. The presented findings here could have clinical implications in the treatment of bone fractures in patients with T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Publicationtype: Journal Article11 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , The decisive early phase of bone regeneration(Springer, 2023-02-01); ; ; ; Bone has a remarkable endogenous regenerative capacity that enables scarless healing and restoration of its prior mechanical function, even under challenging conditions such as advanced age and metabolic or immunological degenerative diseases. However — despite much progress — a high number of bone injuries still heal with unsatisfactory outcomes. The mechanisms leading to impaired healing are heterogeneous, and involve exuberant and non-resolving immune reactions or overstrained mechanical conditions that affect the delicate regulation of the early initiation of scar-free healing. Every healing process begins phylogenetically with an inflammatory reaction, but its spatial and temporal intensity must be tightly controlled. Dysregulation of this inflammatory cascade directly affects the subsequent healing phases and hinders the healing progression. This Review discusses the complex processes underlying bone regeneration, focusing on the early healing phase and its highly dynamic environment, where vibrant changes in cellular and tissue composition alter the mechanical environment and thus affect the signalling pathways that orchestrate the healing process. Essential to scar-free healing is the interplay of various dynamic cascades that control timely resolution of local inflammation and tissue self-organization, while also providing sufficient local stability to initiate endogenous restoration. Various immunotherapy and mechanobiology-based therapy options are under investigation for promoting bone regeneration.Publicationtype: Review Article29 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Clinical and technical validation of novel bite force measuring device for functional analysis after mandibular reconstruction(2023-02-01); ; ; ; Bite force measuring devices that are generally suitable for edentulous patients or patients undergoing mandibular reconstruction are missing. This study assesses the validity of a new bite force measuring device (prototype of loadpad®, novel GmbH) and evaluates its feasibility in patients after segmental mandibular resection. Accuracy and reproducibility were analyzed with two different protocols using a universal testing machine (Z010 AllroundLine, Zwick/Roell, Ulm, Germany). Four groups were tested to evaluate the impact of silicone layers around the sensor: no silicone (“pure”), 2.0 mm soft silicone (“2-soft”), 7.0 mm soft silicone (“7-soft”) and 2.0 mm hard silicone (“2-hard”). Thereafter, the device was tested in 10 patients prospectively who underwent mandibular reconstruction using a fibula free flap. Average relative deviations of the measured force in relation to the applied load reached 0.77% (“7-soft”) to 5.28% (“2-hard”). Repeated measurements in “2-soft” revealed a mean relative deviation of 2.5% until an applied load of 600 N. Maximum bite force decreased postoperatively by 51.8% to a maximum mean bite force of 131.5 N. The novel device guarantees a high accuracy and degree of reproducibility. Furthermore, it offers new opportunities to quantify perioperative oral function after reconstructive surgery of the mandible also in edentulous patients.Publicationtype: Journal Article4