Browsing by Author "Checa Esteban, Sara"
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Publication without files A 3D in silico multi-tissue evolution model highlights the relevance of local strain accumulation in bone fracture remodeling(Frontiers Media SA, 2022-03-31) ;Perier-Metz, Camille ;Corté, Laurent ;Allena, RacheleSince 5–10% of all bone fractures result in non-healing situations, a thorough understanding of the various bone fracture healing phases is necessary to propose adequate therapeutic strategies. In silico models have greatly contributed to the understanding of the influence of mechanics on tissue formation and resorption during the soft and hard callus phases. However, the late-stage remodeling phase has not been investigated from a mechanobiological viewpoint so far. Here, we propose an in silico multi-tissue evolution model based on mechanical strain accumulation to investigate the mechanobiological regulation of bone remodeling during the late phase of healing. Computer model predictions are compared to histological data of two different pre-clinical studies of bone healing. The model predicted the bone marrow cavity re-opening and the resorption of the external callus. Our results suggest that the local strain accumulation can explain the fracture remodeling process and that this mechanobiological response is conserved among different mammal species. Our study paves the way for further understanding of non-healing situations that could help adapting therapeutic strategies to foster bone healing.Publicationtype: Journal ArticleCitation Publisher Version:Frontiers in Bioengineering and Biotechnology 10: 835094 (2022)Publisher DOI:10.3389/fbioe.2022.8350941 - Some of the metrics are blocked by yourconsent settings
Publication without files Age-related changes in the mechanical regulation of bone healing are explained by altered cellular mechanoresponse(Oxford University Press, 2019-10-01) ;Borgiani, Edoardo ;Figge, Christine ;Kruck, Bettina; ; Increasing age is associated with a reduced bone regeneration potential and increased risk of morbidities and mortality. A reduced bone formation response to mechanical loading has been shown with aging, and it remains unknown if the interplay between aging and mechanical stimuli during regeneration is similar to adaptation. We used a combined in vivo/in silico approach to investigate age-related alterations in the mechanical regulation of bone healing and identified the relative impact of altered cellular function on tissue patterns during the regenerative cascade. To modulate the mechanical environment, femoral osteotomies in adult and elderly mice were stabilized using either a rigid or a semirigid external fixator, and the course of healing was evaluated using histomorphometric and micro-CT analyses at 7, 14, and 21 days post-surgery. Computer models were developed to investigate the influence of the local mechanical environment within the callus on tissue formation patterns. The models aimed to identify the key processes at the cellular level that alter the mechanical regulation of healing with aging. Fifteen age-related biological alterations were investigated on two levels (adult and elderly) with a design of experiments setup. We show a reduced response to changes in fixation stability with age, which could be explained by reduced cellular mechanoresponse, simulated as alteration of the ranges of mechanical stimuli driving mesenchymal stem cell differentiation. Cellular mechanoresponse has been so far widely ignored as a therapeutic target in aged patients. Our data hint to mechanotherapeutics as a potential treatment to enhance bone healing in the elderly. © 2019 American Society for Bone and Mineral Research.Publicationtype: Journal ArticleCitation Publisher Version:Journal of Bone and Mineral Research 34 (10): 1923-1937 (2019)Publisher DOI:10.1002/jbmr.38017 - Some of the metrics are blocked by yourconsent settings
Publication without files Aging leads to a dysregulation in mechanically driven bone formation and resorption(Oxford University Press, 2015-10-01) ;Razi, Hajar ;Birkhold, Annette I.; ; ; Physical activity is essential to maintain skeletal mass and structure, but its effect seems to diminish with age. To test the hypothesis that bone becomes less sensitive to mechanical strain with age, we used a combined in vivo/in silico approach. We investigated how maturation and aging influence the mechanical regulation of bone formation and resorption to 2 weeks of noninvasive in vivo controlled loading in mice. Using 3D in vivo morphometrical assessment of longitudinal microcomputed tomography images, we quantified sites in the mouse tibia where bone was deposited or resorbed in response to controlled in vivo loading. We compared the (re)modeling events (formation/resorption/quiescent) to the mechanical strains induced at these sites (predicted using finite element analysis). Mice of all age groups (young, adult, and elderly) responded to loading with increased formation and decreased resorption, preferentially at high strains. Low strains were associated with no anabolic response in adult and elderly mice, whereas young animals showed a strong response. Adult animals showed a clear separation between strain ranges where formation and resorption occurred but without an intermediate quiescent "lazy zone". This strain threshold disappeared in elderly mice, as mechanically induced (re)modeling became dysregulated, apparent in an inability to inhibit resorption or initiate formation. Contrary to what is generally believed until now, aging does not shift the mechanical threshold required to initiate formation or resorption, but rather blurs its specificity. These data suggest that pharmaceutical strategies augmenting physical exercise should consider this dysfunction in the mechanical regulation of bone (re)modeling to more effectively combat age-related bone loss.Publicationtype: Journal ArticleCitation Publisher Version:Journal of Bone and Mineral Research 30 (10): 1864-1873 (2015)Publisher DOI:10.1002/jbmr.25285 - Some of the metrics are blocked by yourconsent settings
Publication without files Anatomic grooved stem mitigates strain shielding compared to established total hip arthroplasty stem designs in finite-element modelsAseptic loosening remains a major problem for uncemented femoral components in primary total hip arthroplasty (THA). Ideally, bone adaptation after THA manifests minimally and local bone density reduction is widely avoided. Different design features may help to approximate initial, post-THA bone strain to levels pre-THA. Strain-shielding effects of different SP-CL stem design features are systematically analyzed and compared to CLS Spotorno and CORAIL using finite element models and physiological musculoskeletal loading conditions. All designs show substantial proximal strain-shielding: 50% reduced medial surface strain, 40–50% reduction at lateral surface, >120 µm/m root mean square error (RMSE) compared to intact bone in Gruen zone 1 and >60 µm/m RMSE in Gruen zones 2, 6, and 7. Geometrical changes (ribs, grooves, cross sections, stem length, anatomic curvature) have a considerable effect on strain-shielding; up to 20%. Combinations of reduced stem stiffness with larger proximal contact area (anatomically curved, grooves) lead to less strain-shielding compared to clinically established implant designs. We found that only the combination of a structurally flexible stem with anatomical curvature and grooves improves strain-shielding compared to other designs. The clinical implications in vivo of this initial strain-shielding difference are currently under evaluation in an ongoing clinical analysis.Publicationtype: Journal ArticleCitation Publisher Version:Scientific Reports 9 (1): 482 (2019)Publisher DOI:10.1038/s41598-018-36503-z3 - Some of the metrics are blocked by yourconsent settings
Publication without files Biomechanical assessment of the validity of sheep as a preclinical model for testing mandibular fracture fixation devices(Frontiers Media SA, 2021-05-06); ; ; ; ; Mandibular fracture fixation and reconstruction are usually performed using titanium plates and screws, however, there is a need to improve current fixation techniques. Animal models represent an important step for the testing of new designs and materials. However, the validity of those preclinical models in terms of implant biomechanics remains largely unknown. In this study, we investigate the biomechanics of the sheep mandible as a preclinical model for testing the mechanical strength of fixation devices and the biomechanical environment induced on mandibular fractures. We aimed to assess the comparability of the biomechanical conditions in the sheep mandible as a preclinical model for human applications of fracture fixation devices and empower analyses of the effect of such defined mechanical conditions on bone healing outcome. We developed 3D finite element models of the human and sheep mandibles simulating physiological muscular loads and three different clenching tasks (intercuspal, incisal, and unilateral). Furthermore, we simulated fractures in the human mandibular body, sheep mandibular body, and sheep mandibular diastema fixated with clinically used titanium miniplates and screws. We compared, at the power stroke of mastication, the biomechanical environment (1) in the healthy mandibular body and (2) at the fracture sites, and (3) the mechanical solicitation of the implants as well as the mechanical conditions for bone healing in such cases. In the healthy mandibles, the sheep mandibular body showed lower mechanical strains compared to the human mandibular body. In the fractured mandibles, strains within a fracture gap in sheep were generally not comparable to humans, while similar or lower mechanical solicitation of the fixation devices was found between the human mandibular body fracture and the sheep mandibular diastema fracture scenarios. We, therefore, conclude that the mechanical environments of mandibular fractures in humans and sheep differ and our analyses suggest that the sheep mandibular bone should be carefully re-considered as a model system to study the effect of fixation devices on the healing outcome. In our analyses, the sheep mandibular diastema showed similar mechanical conditions for fracture fixation devices to those in humans.Publicationtype: Journal ArticleCitation Publisher Version:Frontiers in Bioengineering and Biotechnology 9: 672176 (2021)Publisher DOI:10.3389/fbioe.2021.6721763 - Some of the metrics are blocked by yourconsent settings
Publication 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 ArticleCitation Publisher Version:Computers in Biology and Medicine 168: 107817 (2024)Publisher DOI:10.1016/j.compbiomed.2023.1078172 - Some of the metrics are blocked by yourconsent settings
Publication without files Bone healing in mice : does it follow generic mechano-regulation rules?(University of Nis, 2015-12-01) ;Borgiani, Edoardo; ; Mechanical signals are known to influence bone healing progression. Previous studies have postulated inter-species differences in the mechanical regulation of the bone healing process. The aim of this study is to investigate whether mechanical “rules” explaining tissue formation patterns during bone healing in rat can be translated to a mouse model of bone regeneration. We have used an established mechano-biological computer model that uses finite element techniques to determine the mechanical conditions within the healing region and an agent-based approach to simulate cellular activity. The computer model is set up to simulate the course of bone healing in a femoral osteotomy model stabilized with an external fixator. Computer model predictions are compared to corresponding histological data. Generic mechano-regulation “rules” able to explain bone healing progression in the rat are not able to describe tissue formation over the course of healing in the mouse. According to the differentiation theory proposed by Prendergast, mechanical stimuli within the healing region immediately post-surgery are determined to be favorable for cartilage and fibrous tissue formation. In contrast, in vivo histological data showed initial intramembraneous bone formation at the periosteal side. These results suggest that in mice, bone does not require as much stability as is required in rat to reach timely healing. This finding emphasizes the need to further investigate the species-specific mechano-biological regulation of bone regeneration.Publicationtype: Journal ArticleCitation Publisher Version:Facta Universitatis, Series: Mechanical Engineering 13 (3): 217-227 (2015)6 - Some of the metrics are blocked by yourconsent settings
Publication without files Bone morphogenetic protein 2-induced cellular chemotaxis drives tissue patterning during critical-sized bone defect healing : an in silico study(Springer Nature, 2021-08-01) ;Borgiani, Edoardo; ; Critical-sized bone defects are critical healing conditions that, if left untreated, often lead to non-unions. To reduce the risk, critical-sized bone defects are often treated with recombinant human BMP-2. Although enhanced bone tissue formation is observed when BMP-2 is administered locally to the defect, spatial and temporal distribution of callus tissue often differs from that found during regular bone healing or in defects treated differently. How this altered tissue patterning due to BMP-2 treatment is linked to mechano-biological principles at the cellular scale remains largely unknown. In this study, the mechano-biological regulation of BMP-2-treated critical-sized bone defect healing was investigated using a multiphysics multiscale in silico approach. Finite element and agent-based modeling techniques were combined to simulate healing within a critical-sized bone defect (5 mm) in a rat femur. Computer model predictions were compared to in vivo microCT data outcome of bone tissue patterning at 2, 4, and 6 weeks postoperation. In vivo, BMP-2 treatment led to complete healing through periosteal bone bridging already after 2 weeks postoperation. Computer model simulations showed that the BMP-2 specific tissue patterning can be explained by the migration of mesenchymal stromal cells to regions with a specific concentration of BMP-2 (chemotaxis). This study shows how computational modeling can help us to further understand the mechanisms behind treatment effects on compromised healing conditions as well as to optimize future treatment strategies.Publicationtype: Journal ArticleCitation Publisher Version:Biomechanics and Modeling in Mechanobiology 20 (4): 1627-1644 (2021)Publisher DOI:10.1007/s10237-021-01466-02 - Some of the metrics are blocked by yourconsent settings
Publication without files Capillary network formation during tissue differentiation : a mechano-biological modelAngiogenesis, the formation of new capillaries from pre-existing vessels, plays a critical role during bone regeneration and repair. In addition to an appropriate mechanical environment, sufficient supply of oxygen and nutrients is critical for bone formation. Mechano-biological models have been previously used to predict the time course of the differentiation process with the mechanical environment as the only regulator of cell activity. Here we propose a mechano-biological model for tissue differentiation where cell activity is regulated by both the local mechanical environment and the local vascularity. Results show a significant effect of the morphology of the new capillary network on bone formation and heterogeneous distributions of cells similar to those seen in histological studies. © 2009 Springer Berlin Heidelberg.Publicationtype: Conference PaperCitation Publisher Version:4th European Conference of the International Federation for Medical and Biological Engineering : ECIFMBE 2008 23–27 November 2008 Antwerp, Belgium / edited by R. Magjarevic, J. H. Nagel, Jos Vander Sloten, Pascal Verdonck, Marc Nyssen, Jens Haueisen. - Berlin, Heidelberg : Springer Berlin Heidelberg, 2009.- S. 2195-2199Publisher DOI:10.1007/978-3-540-89208-3_5252 - Some of the metrics are blocked by yourconsent settings
Publication 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 ArticleCitation Publisher Version:Diagnostics 13 (4): 586 (2023)Publisher DOI:10.3390/diagnostics13040586 - Some of the metrics are blocked by yourconsent settings
Publication without files Comparative study of CAD/CAM reconstruction and miniplates for patient-specific fixation in LCL-type mandibular reconstruction(2024); ;Fenske, Jakob; ; ; ; ; ; ; 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 ArticleCitation Publisher Version:Frontiers in Oncology 14: 1438269 (2024)Publisher DOI:10.3389/fonc.2024.14382695 - Some of the metrics are blocked by yourconsent settings
Publication without files Computational analyses of different intervertebral cages for lumbar spinal fusion(Elsevier, 2015-09-18) ;Bashkuev, Maxim; ;Postigo, Sergio; Lumbar spinal fusion is the most common approach for treating spinal disorders such as degeneration or instability. Although this procedure has been performed for many years, there are still important challenges that must be overcome and questions that need to be addressed regarding the high rates of non-union. The present finite element model study aimed to investigate the influence of different cage designs on the fusion process. An axisymmetric finite element model of a spinal segment with an interbody fusion cage was used. The fusion process was based on an existing mechano-regulation algorithm for tissue formation. With this model, the following principal concepts of cage design were investigated: (1) different cage geometries with constant compressive stiffness and (2) cage designs optimized to provide the ideal mechanical stimulus for bone formation, first at the beginning of fusion and then throughout the entire fusion process. The cage geometry substantially influenced the fusion outcome. A cage that created an optimized initial mechanical stimulus did not necessarily lead to accelerated fusion, but rather resulted in delayed fusion or non-union. In contrast, a cage made of a degradable material produced a significantly higher amount of bone and resulted in higher segmental stiffness. However, different compressive loads (250, 500 and 1000. N) substantially affected the amount of newly formed bone tissue. The results of the present study suggest that aiming for an optimal initial mechanical stimulus may be misleading because the initial mechanical environment is not preserved throughout the bone modeling process.Publicationtype: Journal ArticleCitation Publisher Version:Journal of Biomechanics 48 (12): 7265 (2015)Publisher DOI:10.1016/j.jbiomech.2015.06.02417 - Some of the metrics are blocked by yourconsent settings
Publication without files Computational design and evaluation of the mechanical and electrical behavior of a piezoelectric scaffold : a preclinical study(Frontiers Media SA, 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 ArticleCitation Publisher Version:Frontiers in Bioengineering and Biotechnology 11: 1261108 (2024-01-11)Publisher DOI:10.3389/fbioe.2023.12611082 - Some of the metrics are blocked by yourconsent settings
Publication without files Computational modeling to quantify the contributions of VEGFR1, VEGFR2, and lateral inhibition in sprouting angiogenesisSprouting angiogenesis is a necessary process in regeneration and development as well as in tumorigenesis. VEGF-A is the main pro-angiogenic chemoattractant and it can bind to the decoy receptor VEGFR1 or to VEGFR2 to induce sprouting. Active sprout cells express Dll4, which binds to Notch1 on neighboring cells, in turn inhibiting VEGFR2 expression. It is known that the balance between VEGFR2 and VEGFR1 determines tip selection and network architecture, however the quantitative interrelationship of the receptors and their interrelated balances, also with relation to Dll4-Notch1 signaling, remains yet largely unknown. Here, we present an agent-based computer model of sprouting angiogenesis, integrating VEGFR1 and VEGFR2 in a detailed model of cellular signaling. Our model reproduces experimental data on VEGFR1 knockout. We show that soluble VEGFR1 improves the efficiency of angiogenesis by directing sprouts away from existing cells over a wide range of parameters. Our analysis unravels the relevance of the stability of the active notch intracellular domain as a dominating hub in this regulatory network. Our analysis quantitatively dissects the regulatory interactions in sprouting angiogenesis. Because we use a detailed model of intracellular signaling, the results of our analysis are directly linked to biological entities. We provide our computational model and simulation engine for integration in complementary modeling approaches.Publicationtype: Journal ArticleCitation Publisher Version:Frontiers in Physiology 10 (3): 288 (2019)Publisher DOI:10.3389/fphys.2019.002881 - Some of the metrics are blocked by yourconsent settings
Publication without files Computational models of tissue differentiationReaders of this chapter will learn about our approach to computer simulation of tissue differentiation in response to mechanical forces. It involves defining algorithms for mechanoregulation of each of following cell activities: proliferation, apoptosis, migration, and differentiation using a stimulus based on a combination of strain and fluid flow (Prendergast et al., J. Biomech., 1997)-algorithms are based on a lattice-modelling which also facilitates building algorithms for complex processes such as angiogenesis. The algorithms are designed to be collaboratable individually. They can be combined to create a computational simulation method for tissue differentiation, using finite element analysis to compute the mechanical stimuli in even quite complex biomechanical environments. Examples are presented of the simulation method in use. © 2010 Springer Science+Business Media B.V.Publicationtype: Book partCitation Publisher Version:In: Computational Modeling in Biomechanics / edited by Suvranu De, Farshid Guilak, Mohammad Mofrad R. K.. - Dordrecht : Springer Science+Business Media B.V, 2010. - S. 353-372Publisher DOI:10.1007/978-90-481-3575-2_123 - Some of the metrics are blocked by yourconsent settings
Publication without files Computational techniques for selection of biomaterial scaffolds for tissue engineering(Springer, 2011-01-01); ;Sandino, Clara ;Byrne, Damien P.; ; Prendergast, Patrick J.Computational tools are nowadays an indispensable tool for engineering design. Tissue engineering is an interdisciplinary field which so far has been mainly limited to experimental investigations. Here we present several examples of how computer models can be used in the design of tissue engineering scaffolds. Investigations of the effect of scaffold porosity, dissolution rate and/or scaffold material properties on processes such as cell differentiation, migration and angiogenesis are presented. Current limitations and future perspectives in the development and potential application of these models are described.Publicationtype: Conference PaperCitation Publisher Version:Computational Methods in Applied Sciences 20: 55-69 (2011)Publisher DOI:10.1007/978-94-007-1254-6_411 - Some of the metrics are blocked by yourconsent settings
Publication without files Computer-assisted preoperative planning of bone fracture fixation surgery : a state-of-the-art reviewBackground: Bone fracture fixation surgery is one of the most commonly performed surgical procedures in the orthopedic field. However, fracture healing complications occur frequently, and the choice of the most optimal surgical approach often remains challenging. In the last years, computational tools have been developed with the aim to assist preoperative planning procedures of bone fracture fixation surgery. Objectives: The aims of this review are 1) to provide a comprehensive overview of the state-of-the-art in computer-assisted preoperative planning of bone fracture fixation surgery, 2) to assess the clinical feasibility of the existing virtual planning approaches, and 3) to assess their clinical efficacy in terms of clinical outcomes as compared to conventional planning methods. Methods: A literature search was performed in the MEDLINE-PubMed, Ovid-EMBASE, Ovid-EMCARE, Web of Science, and Cochrane libraries to identify articles reporting on the clinical use of computer-assisted preoperative planning of bone fracture fixation. Results: 79 articles were included to provide an overview of the state-of-the art in virtual planning. While patient-specific geometrical model construction, virtual bone fracture reduction, and virtual fixation planning are routinely applied in virtual planning, biomechanical analysis is rarely included in the planning framework. 21 of the included studies were used to assess the feasibility and efficacy of computer-assisted planning methods. The reported total mean planning duration ranged from 22 to 258 min in different studies. Computer-assisted planning resulted in reduced operation time (Standardized Mean Difference (SMD): -2.19; 95% Confidence Interval (CI): -2.87, -1.50), less blood loss (SMD: -1.99; 95% CI: -2.75, -1.24), decreased frequency of fluoroscopy (SMD: -2.18; 95% CI: -2.74, -1.61), shortened fracture healing times (SMD: -0.51; 95% CI: -0.97, -0.05) and less postoperative complications (Risk Ratio (RR): 0.64, 95% CI: 0.46, 0.90). No significant differences were found in hospitalization duration. Some studies reported improvements in reduction quality and functional outcomes but these results were not pooled for meta-analysis, since the reported outcome measures were too heterogeneous. Conclusion: Current computer-assisted planning approaches are feasible to be used in clinical practice and have been shown to improve clinical outcomes. Including biomechanical analysis into the framework has the potential to further improve clinical outcome.Publicationtype: Review ArticleCitation Publisher Version:Frontiers in Bioengineering and Biotechnology 10: 1037048 (2022)Publisher DOI:10.3389/fbioe.2022.10370484 - Some of the metrics are blocked by yourconsent settings
Publication without files Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a lattice-modeling approachIt is well established that the mechanical environment modulates tissue differentiation, and a number of mechanoregulatory theories for describing the process have been proposed. In this study, simulations of an in vivo bone chamber experiment were performed that allowed direct comparison with experimental data. A mechanoregulation theory for mesenchymal stem cell differentiation based on a combination of fluid flow and shear strain (computed using finite element analysis) was implemented to predict tissue differentiation inside mechanically controlled bone chambers inserted into rat tibae. To simulate cell activity, a lattice approach with stochastic cell migration, proliferation, and selected differentiation was adopted; because of its stochastic nature, each run of the simulation gave a somewhat different result. Simulations predicted the load-dependency of the tissue differentiation inside the chamber and a qualitative agreement with histological data; however, the full variability found between specimens in the experiment could not be predicted by the mechanoregulation algorithm. This result raises the question whether tissue differentiation predictions can be linked to genetic variability in animal populations. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.Publicationtype: Journal ArticleCitation Publisher Version:Journal of Orthopaedic Research 27 (12): 1659-1666 (2009)Publisher DOI:10.1002/jor.209261 - Some of the metrics are blocked by yourconsent settings
Publication without files Cortical bone adaptation to a moderate level of mechanical loading in male Sost deficient mice(Springer Nature, 2020-12-01) ;Yang, Haisheng ;Büttner, Alexander ;Albiol, Laia ;Julien, Catherine ;Thiele, Tobias ;Figge, Christine ;Kramer, Ina ;Kneissel, Michaela; ; Loss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.Publicationtype: Journal ArticleCitation Publisher Version:Scientific Reports 10 (1): 22299 (2020)Publisher DOI:10.1038/s41598-020-79098-04 - Some of the metrics are blocked by yourconsent settings
Publication without files The decisive early phase of bone regeneration(Springer Nature, 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 ArticleCitation Publisher Version:Nature Reviews Rheumatology 19 (2): 78-95 (2023)Publisher DOI:10.1038/s41584-022-00887-07