Bone Response Research Articles

The effects of endurance trainability phenotype, sex, and interval running training on bone collagen synthesis in adult rats

Bone is influenced by many factors such as genetics and mechanical loading, but the short-term physiological effects of these factors on bone (re)modelling are not well characterised. This study investigated the effects of endurance trainability phenotype, sex, and interval running training (7-week intervention) on bone collagen formation in rats using a deuterium oxide stable isotope tracer method. Bone samples of the femur diaphysis, proximal tibia, mid-shaft tibia, and distal tibia were collected after necropsy from forty-six 9 ± 3-month male and female rats selectively bred for yielding low (LRT) or high (HRT) responses to endurance training. Bone collagen proteins were isolated and hydrolysed, and fractional synthetic rates (FSRs) were determined by the incorporation of deuterium into protein-bound alanine via GC-pyrolysis-IRMS. There was a significant large main effect of phenotype at the femur site (p < 0.001; η2g = 0.473) with HRT rats showing greater bone collagen FSRs than LRT rats. There was a significant large main effect of phenotype (p = 0.008; η2g = 0.178) and a significant large main effect of sex (p = 0.005; η2g = 0.196) at the proximal site of the tibia with HRT rats showing greater bone collagen FSRs than LRT rats, and male rats showing greater bone collagen FSRs compared to female rats. There was a significant large main effect of training at the mid-shaft site of the tibia (p = 0.012; η2g = 0.159), with rats that underwent interval running training having greater bone collagen FSRs than control rats. Similarly, there was a significant large main effect of training at the distal site of the tibia (p = 0.050; η2g = 0.156), with rats in the interval running training group having greater bone collagen FSRs compared to rats in the control group. Collectively, this evidence highlights that bone responses to physiological effects are site-specific, indicating that interval running training has positive effects on bone collagen synthesis at the tibial mid-shaft and distal sites, whilst genetic factors affect bone collagen synthesis at the femur diaphysis (phenotype) and proximal tibia (phenotype and sex) in rats.

An Opinion on the Interpretation of Bone Turnover Markers Following Acute Exercise or Nutrition Intervention and Considerations for Applied Research.

It is important for athlete and public health that we continue to develop our understanding of the effects of exercise and nutrition on bone health. Bone turnover markers (BTMs) offer an opportunity to accelerate the progression of bone research by revealing a bone response to exercise and nutrition stimuli far more rapidly than current bone imaging techniques. However, the association between short-term change in the concentration of BTMs and long-term bone health remains ambiguous. Several other limitations also complicate the translation of acute BTM data to applied practice. Importantly, several incongruencies exist between the effects of exercise and nutrition stimuli on short-term change in BTM concentration compared with long-term bone structural outcomes to similar stimuli. There are many potential explanations for these inconsistencies, including that short-term study designs fail to encompass a full remodeling cycle. The current article presents the opinion that data from relatively acute studies measuring BTMs may not be able to reliably inform applied practice aiming to optimize bone health. There are important factors to consider when interpreting or translating BTM data and these are discussed.

Multifaceted bone response to immunomodulatory magnesium implants: Osteopromotion at the interface and adipogenesis in the bone marrow

Orthopedic implants made of biodegradable magnesium (Mg) provide an alternative to nondegradable implants for fracture repair. Widely reported to be pro-osteogenic, Mg implants are also believed to be anti-inflammatory and anti-osteoclastic, but this is difficult to reconcile with the early clinical inflammation observed around these implants. Here, by surveying implant healing in a rat bone model, we determined the cellular responses and structural assembly of bone correlated with the surface changes of Mg implants inherent in degradation. We show that, compared to titanium, both high-purity (99.998 %) and clinical-grade, rare earth-alloyed (MgYREZr) Mg implants create an initial, transient proinflammatory environment that facilitates inducible nitric oxide synthase-mediated macrophage polarization, osteoclastogenesis, and neoangiogenesis programs. While this immunomodulation subsequently reinforces reparative osteogenesis at the surface of both Mg implants, the faster degradation of high-purity Mg implants, but not MgYREZr implants, elicits a compositional alteration in the interfacial bone and a previously unknown proadipogenic response with persistent low-grade inflammation in the surrounding bone marrow. Beyond the need for rigorous tailoring of Mg implants, these data highlight the need to closely monitor osseointegration not only at the immediate implant surface but also in the peri-implant bone and adjacent bone marrow.

Periosteum response to static forces stimulates cortical drifting: A new orthopedic target

The mechanism of cortical bone adaptation to static forces is not well understood. This is an important process because static forces are applied to the cortical bone in response to the growth of soft tissues and during Orthodontic and Orthopedic corrections. The aim of this study was to investigate the cortical bone response to expanding forces applied to the maxilla. Overall, 375 adult Sprague-Dawley rats were divided into three groups: 1) static force group, 2) static force plus stimulation group, and 3) sham group. In addition to static force across the maxilla, some animals were exposed to anti-inflammatory medication. Samples were collected at different time points and evaluated by micro-computed tomography, fluorescence microscopy, immunohistochemistry, and gene and protein analyses. The application of expansion forces to the maxilla increased inflammation in the periosteum and activated osteoclasts on the surface of the cortical plate. This activation was independent of the magnitude of tooth movement but followed the pattern of skeletal displacement. Bone formation on the surface of the cortical plate occurred at a later stage and resulted in the relocation of the cortical boundary of the maxilla and cortical drifting. This study demonstrates that cortical bone adaptation to static forces originates from the periosteum, and it is an inflammatory-based phenomenon that can be manipulated by the clinician. Our findings support a new theory for cortical adaptation to static forces and an innovative clinical approach to promote cortical drifting through periosteal stimulation. Being able to control cortical drift can have a significant impact on clinical orthodontic and dentofacial orthopedics by allowing corrections of severe deformities without the need for maxillofacial surgery.

The role of Clec11a in bone construction and remodeling.

Bone is a dynamically active tissue whose health status is closely related to its construction and remodeling, and imbalances in bone homeostasis lead to a wide range of bone diseases. The sulfated glycoprotein C-type lectin structural domain family 11 member A (Clec11a) is a key factor in bone mass regulation that significantly promotes the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts and stimulates chondrocyte proliferation, thereby promoting longitudinal bone growth. More importantly, Clec11a has high therapeutic potential for treating various bone diseases and can enhance the therapeutic effects of the parathyroid hormone against osteoporosis. Clec11a is also involved in the stress/adaptive response of bone to exercise via mechanical stimulation of the cation channel Pieoz1. Clec11a plays an important role in promoting bone health and preventing bone disease and may represent a new target and novel drug for bone disease treatment. Therefore, this review aims to explore the role and possible mechanisms of Clec11a in the skeletal system, evaluate its value as a potential therapeutic target against bone diseases, and provide new ideas and strategies for basic research on Clec11a and preventing and treating bone disease.

Three-dimensional-printed femoral diaphysis for biomechanical testing-Optimization and validation.

Polylactic acid (PLA) models of normal human femoral diaphyses were designed using three-dimensional (3D) printing technology to create inexpensive, accessible, and reproducible specimens for flexural biomechanical studies. These models were subjected to three-point bending and their response to loading was characterized. The anisotropic mechanical behavior of the 3D-printed femurs and the influence of printing orientations, infill density, wall layers, resolution, and other printing parameters were explored to develop a design space. The objective of the design space was set to emulate the flexural biomechanical response of the normal human femur bones. Results show the 3D-printed PLA diaphyseal femurs with 5% infill density, two-four wall layers, and a resolution of 200 µm resulted in a flexural strength of 184.8 ± 8.18 MPa. Models with 20% infill density and six wall layers resulted in a flexural modulus of 18.54 ± 0.543 GPa. These results emulate the biomechanical response of the normal human femur, as determined by historical target values derived from prior cadaveric and 3D printing data. With further research, inclusive of modeling the proximal and distal femur and more comprehensive biomechanical testing, 3D-printed femurs may ultimately serve as a cheap, accessible biomechanical resource for surgeons and researchers.

Analysis of the milling response of an artificial temporal bone developed for otologic surgery in comparison with human cadaveric samples

Temporal-bone milling is a delicate process commonly performed during otologic surgery to gain access to the middle and inner ear structures. Because of the numerous at-risk structures of this anatomic area, extensive surgeon training is required. Artificial temporal bones offer an interesting alternative to cadaveric training. However, the evaluation of such simulators has not been systematic, with an absence of objective validation of their milling response, especially in a surgical context.By measuring the milling forces obtained during the classical steps of otologic surgery on six 3D-printed and three cadaveric temporal bones, this work aims at evaluating the ability of the OTOtwin® synthetic temporal bone to reproduce human bone behavior.A better repeatability was obtained for artificial bones than for cadaveric ones. However, the level of forces recorded during artificial bone milling was close to the one measured with cadaveric samples. The effects of both surgical phase and irrigation on milling force levels were also quantified. The experiments conducted in this study confirmed the suitability of OTOtwin® temporal bone model for both otologic surgery training and research purposes. Valuable insights were also gained from this study regarding the understanding of the otologic milling process.

Analysis of synovitis patterns in early RA supports the importance of joint-specific factors

BackgroundRheumatoid arthritis (RA) is classically considered a systemic disorder, but the role of local factors in driving synovial inflammation is increasingly being recognized. These joint-specific factors may consequently modulate disease phenotype. ObjectivesOur goal was to study the spatial distribution of swelling, tenderness and erosions in a large cohort of early RA (ERA) patients, to assess for patterns of simultaneously-involved joint clusters. We also aimed to investigate the link between arthritis localization and phenotypic features such as bone erosions and response to methotrexate therapy. MethodsDMARD-naive patients from the ERA UCLouvain Brussels cohort were included. Forty-four joints were clinically assessed for swelling and tenderness before treatment, and 6 months later for methotrexate-treated patients. Clusters of joints were identified using Principal component analysis and Cramer's correlation coefficients. Frequency of bone erosions and joint-specific response to methotrexate were compared across different clusters. Results452 ERA patients were included. Analysis of the spatial distribution of swelling and tenderness allowed for the identification of 3 joint clusters that showed significant simultaneous involvement: (i) MTP1–5 joints, (ii) hand joints (MCPs and PIPs), and (iii) larger joints. These clusters were associated with different susceptibility to bone erosions and distinct clinical features, but similar local response (joint swelling resolution) to methotrexate. ConclusionThis is the first study investigating the spatial distribution of arthritis in a large cohort of early RA using an unbiased approach. We identify clusters of simultaneously involved joints, supporting the importance of local factors in driving synovitis in RA.

Investigating adhesion of primary human gingival fibroblasts and osteoblasts to orthodontic mini-implants by scanning electron microscopy

Miniscrews offer controlled anchorage and thus optimize tooth movement in orthodontic treatment. Nevertheless, failures such as soft tissue problems, instability due to loosening, partial osseointegration, or even device fracture can occur. While clinical technique can play a role in some of these problems, the manufacturer’s design and material choice influence how the implant interacts with the surrounding tissue. In some cases, the design and material may trigger unwanted bone and soft tissue responses. This in vitro study investigates how the implant surface affects cell adhesion and growth of human primary fibroblasts and osteoblasts on commercially available orthodontic TiAl6V4 miniscrews from three producers: tomas-pin SD N 08 (Dentaurum), OrthoEasy Pin (Forestadent), and Dual Top G2 (Promedia, Jeil Medical). Cell–implant interaction at the top, neck, and drilling part of the screws was assessed qualitatively by scanning electron microscopy. While both cell types adhered to and grew on all products, subtle differences in cell shape and spreading were detected, depending on the microstructure of the implant surface. This indicates that cell adhesion to implant surfaces can be controlled by manipulating the machining conditions.

Disparate effects of sclerostin deletion on alveolar bone and cellular cementum in mice.

Cellular cementum (CC) includes cementocytes, cells suspected to regulate CC formation or resorption as osteocytes do in bone. Sclerostin (SOST) is a secreted negative regulator of Wnt/β-catenin signaling expressed by osteocytes andcementocytes. Osteocyte SOST expression reduces bone formation. We investigated the functional importance of SOST in CC compared with alveolar bone (AB) using a Sost knockout (Sost-/-) mouse model to better understand the role of cementocytes in CC. Mandibles and femurs of Sost-/- and wild-type (WT) mice were analyzed at 42 and 120 days postnatal (dpn). Maxillary first molars were bilaterally extracted at 42 dpn and both AB healing (maxillary molar sockets) and CC apposition (mandibular first molars) were examined at 21 days post-procedure. Analyses included micro-computed tomography, histology, and immunohistochemistry. Femur cortical and trabecular bone and mandibular bone volumes were similarly increased in Sost-/- versus WT mice at 42 and/or 120 dpn. In contrast to previous reports, CC was not increased by Sost-/- at either age. We conducted challenge experiments on AB and CC to explore tissue-specific responses. Post-extraction AB healing was improved by Sost deletion. In contrast, experimentally-induced apposition in molars failed to stimulate increased CC formation in Sost-/- versus WT mice. Wnt pathway markers AXIN2 and DKK1, which were increased in Sost-/- versus WT AB osteocytes, were unchanged in cementocytes. These data indicate CC is less responsive than AB to SOST deletion. Within the study limitations, these results do not support cementocytes as critical for directing increased CC formation. Sclerostin is a protein known to inhibit bone formation, and removing sclerostin leads to more bone formation. Cementum is the thin layer that covers the surface of the tooth's root. Previous studies suggest that inhibiting sclerostin can similarly increase the amount of cementum. We wanted to compare the response of cementum and bone when sclerostin is absent to understand similarities and differences between these two tissues. In this study, we removed the Sost gene (the gene which produces sclerostin) in mice. We found that mice without sclerostin have more bone in their legs and jaws. Moreover, mice without sclerostin also healed better after tooth removal compared with normal mice. Surprisingly, unlike previous studies, we found that the amount of cementum was not different in mice without sclerostin compared with normal mice. Additionally, we challenged the cementum by taking out the opposing tooth to cause the first mandibular molar to move up by building more cementum. Even with this challenge, we found no difference in the amount of cementum in mice lacking sclerostin compared with normal mice. Therefore, we conclude here that cementum is less sensitive to the absence of sclerostin compared with bone.

Metabolic bone imaging and its relationship with biomechanics

ObjectiveThis mini review delves into the mechanisms of [18F]Sodium Fluoride positron emission tomography ([18F]NaF PET), which, by interrogating areas of newly mineralizing bone, provides a valuable tool to study the joint response to loading and areas of altered whole-joint function in osteoarthritis (OA). DesignThe review consolidates and discusses findings from both preclinical and clinical studies that utilize [18F]NaF PET to evaluate the bone response to various loading paradigms. It also briefly reviews technical considerations for PET imaging and discusses its strong potential as a tool in the quest to understand bone metabolism in the context of loading and osteoarthritis. ResultsWhile considering previous studies, technical considerations and potential new applications of this methodology are also discussed. [18F]NaF PET/MRI reveals localized, load-related bone responses after exercise, providing insights into early OA progression. In human studies, significant increases in tracer uptake are observed in areas affected by OA pathology, driven by bone perfusion and blood volume. Future work to examine the relationship between metabolic bone response to exercise and the bone loading environment is needed. ConclusionsIntegrating [18F]NaF PET/MRI with advanced biomechanical modeling holds promise for guiding clinical management of OA, primarily by examining the relationship between bone, soft tissues of the joint, and loading forces.

Mesoscale characterization of osseointegration around an additively manufactured genistein-coated implant

Given the hierarchical nature of bone and bone interfaces, osseointegration, namely the formation of a direct bone-implant contact, is best evaluated using a multiscale approach. However, a trade-off exists between field of view and spatial resolution, making it challenging to image large volumes with high resolution. In this study, we combine established electron microscopy techniques to probe bone-implant interfaces at the microscale and nanoscale with plasma focused ion beam-scanning electron microscopy (PFIB-SEM) tomography to evaluate osseointegration at the mesoscale. This characterization workflow is demonstrated for bone response to an additively manufactured Ti-6Al-4V implant which combines engineered porosity to facilitate bone ingrowth and surface functionalization via genistein, a phytoestrogen, to counteract bone loss in osteoporosis. SEM demonstrated new bone formation at the implant site, including in the internal implant pores. At the nanoscale, scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the gradual nature of the bone-implant interface. By leveraging mesoscale analysis with PFIB-SEM tomography that captures large volumes of bone-implant interface with nearly nanoscale resolution, the presence of mineral ellipsoids varying in size and orientation was revealed. In addition, a well-developed lacuno-canalicular network and mineralization fronts directed both towards the implant and away from it were highlighted.

Elastic response of trabecular bone under compression calculated using the firm and floppy boundary lattice element method

Micro-Finite Element analysis (μFEA) has become widely used in biomechanical research as a reliable tool for the prediction of bone mechanical properties within its microstructure such as apparent elastic modulus and strength. However, this method requires substantial computational resources and processing time. Here, we propose a computationally efficient alternative to FEA that can provide an accurate estimation of bone trabecular mechanical properties in a fast and quantitative way. A lattice element method (LEM) framework based on the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) open-source software package is employed to calculate the elastic response of trabecular bone cores. A novel procedure to handle pore-material boundaries is presented, referred to as the Firm and Floppy Boundary LEM (FFB-LEM). Our FFB-LEM calculations are compared to voxel- and geometry-based FEA benchmarks incorporating bovine and human trabecular bone cores imaged by micro Computed Tomography (μCT). Using 14 computer cores, the apparent elastic modulus calculation of a trabecular bone core from a μCT-based input with FFB-LEM required about 15 min, including conversion of the μCT data into a LAMMPS input file. In contrast, the FEA calculations on the same system including the mesh generation, required approximately 30 and 50 min for voxel- and geometry-based FEA, respectively. There were no statistically significant differences between FFB-LEM and voxel- or geometry-based FEA apparent elastic moduli (+24.3% or +7.41%, and +0.630% or -5.29% differences for bovine and human samples, respectively).

Clinical spectrum of rare bone fragility disorders and response to bisphosphonate treatment: a retrospective study.

Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by brittle bones. Though genetic mutations in COL1A1 and COL1A2 account for approximately 85-90% of OI cases, there are now more than twenty genes described, responsible for rare forms of OI. Treatment is based on the use of bisphosphonates and though it is well established that they increase lumbar spine (LS) bone mineral density (BMD), the clinical impact on fracture reduction is still debated.In this study, we investigated the clinical characteristics of 38 patients with a bone fragility disorder that had variants in non-COL1A1/COL1A2 genes in order to study genotype-phenotype correlations, as the natural history of these rare forms is still not well known. We then studied the usefulness of bisphosphonate treatment by evaluating the effects on LS BMD, annual non-vertebral fracture rate, bone turnover markers and height. This study enabled us to better define the natural history of patients with non-COL1 pathogenic variants. Patients with CRTAP and TMEM38B variants consistently had a prenatal presentation with a short (<3rd p) and bowed femur. Importantly, this prenatal involvement does not predict the postnatal severity of the disease. Regarding treatment by bisphosphonates, all patients showed a significant increase in LS BMD while treated and this increase was dependent on the dose received. The increase in LS BMD also translated in a reduction of fracture rate during treatment. Finally, our study showed that the earlier bisphosphonates are initiated, the greater the fracture rate is reduced.

Biphasic bone substitutes coated with PLGA incorporating therapeutic ions Sr2+ and Mg2+: cytotoxicity cascade and in vivo response of immune and bone regeneration.

The incorporation of bioactive ions into biomaterials has gained significant attention as a strategy to enhance bone tissue regeneration on the molecular level. However, little knowledge exists about the effects of the addition of these ions on the immune response and especially on the most important cellular regulators, the macrophages. Thus, this study aimed to investigate the in vitro cytocompatibility and in vivo regulation of bone remodeling and material-related immune responses of a biphasic bone substitute (BBS) coated with metal ions (Sr2+/Mg2+) and PLGA, using the pure BBS as control group. Initially, two cytocompatible modified material variants were identified according to the in vitro results obtained following the DIN EN ISO 10993-5 protocol. The surface structure and ion release of both materials were characterized using SEM-EDX and ICP-OES. The materials were then implanted into Wistar rats for 10, 30, and 90days using a cranial defect model. Histopathological and histomorphometrical analyses were applied to evaluate material degradation, bone regeneration, osteoconductivity, and immune response. The findings revealed that in all study groups comparable new bone formation were found. However, during the early implantation period, the BBS_Sr2+ group exhibited significantly faster regeneration compared to the other two groups. Additionally, all materials induced comparable tissue and immune responses involving high numbers of both pro-inflammatory macrophages and multinucleated giant cells (MNGCs). In conclusion, this study delved into the repercussions of therapeutic ion doping on bone regeneration patterns and inflammatory responses, offering insights for the advancement of a new generation of biphasic calcium phosphate materials with potential clinical applicability.

Aging alters the subchondral bone response 7 days after noninvasive traumatic joint injury in C57BL/6JN mice.

Posttraumatic osteoarthritis (PTOA) commonly develops following anterior cruciate ligament (ACL) injuries, affecting around 50% of individuals within 10-20 years. Recent studies have highlighted early changes in subchondral bone structure after ACL injury in adolescent or young adult mice, which could contribute to the development of PTOA. However, ACL injuries do not only occur early in life. Middle-aged and older patients also experience ACL injuries and PTOA, but whether the aged subchondral bone also responds rapidly to injury is unknown. This study utilized a noninvasive, single overload mouse injury model to assess subchondral bone microarchitecture, turnover, and material properties in both young adults (5 months) and early old age (22 months) female C57BL/6JN mice at 7 days after injury. Mice underwent either joint injury (i.e., produces ACL tears) or sham injury procedures on both the loaded and contralateral limbs, allowing evaluation of the impacts of injury versus loading. The subchondral bone response to ACL injury is distinct for young adult and aged mice. While 5-month mice show subchondral bone loss and increased bone resorption postinjury, 22-month mice did not show loss of bone structure and had lower bone resorption. Subchondral bone plate modulus increased with age, but not with injury. Both ages of mice showed several bone measures were altered in the contralateral limb, demonstrating the systemic skeletal response to joint injury. These data motivate further investigation to discern how osteochondral tissues differently respond to injury in aging, such that diagnostics and treatments can be refined for these demographics.

ESMAC Best Paper Award 2023: Increased knee flexion in participants with cerebral palsy results in altered stresses at the distal femoral growth plate compared to a typically developing cohort

IntroductionFemoral deformities are highly prevalent in children with cerebral palsy (CP) and can have a severe impact on patients’ gait abilities. While the mechanical stress regime within the distal femoral growth plate remains underexplored, understanding it is crucial given bone's adaptive response to mechanical stimuli. We quantified stresses at the distal femoral growth plate to deepen our understanding of the relationship between healthy and pathological gait patterns, internal loading, and femoral growth patterns. MethodsThis study included three-dimensional motion capture data and magnetic resonance images of 13 typically developing children and twelve participants with cerebral palsy. Employing a multi-scale mechanobiological approach, integrating musculoskeletal simulations and subject-specific finite element analysis, we investigated the orientation of the distal femoral growth plate and the stresses within it. Limbs of participants with CP were grouped depending on their knee flexion kinematics during stance phase as this potentially changes the stresses induced by knee and patellofemoral joint contact forces. ResultsDespite similar growth plate orientation across groups, significant differences were observed in the shape and distribution of growth values. Higher growth rates were noted in the anterior compartment in CP limbs with high knee flexion while CP limbs with normal knee flexion showed high similarity to the group of healthy participants. DiscussionResults indicate that the knee flexion angle during the stance phase is of high relevance for typical bone growth at the distal femur. The evaluated growth rates reveal plausible results, as long-term promoted growth in the anterior compartment leads to anterior bending of the femur which was confirmed for the group with high knee flexion through analyses of the femoral geometry. The framework for these multi-scale simulations has been made accessible on GitHub, empowering peers to conduct similar mechanobiological studies. Advancing our understanding of femoral bone development could ultimately support clinical decision-making.

Development of bone surrogates by material extrusion-based additive manufacturing to mimic flexural mechanical behaviour and fracture prediction via phase-field approach

Background and objectiveThe limited availability of human bone samples for investigation leads to the demand for alternatives. Bone surrogates are crucial in promoting research on the intricate mechanics of osseous tissue. However, solutions are restricted to commercial brands, which frequently fail to faithfully replicate the mechanical response of bone, or oversimplified customised simulants designed for a specific application. The manufacturing and assessment of reliable bone surrogates made of polylactic acid via material extrusion-based additive manufacturing are presented in this work. MethodsAn experimental and numerical study with 3D-printed dog-bone and prismatic specimens was carried out to characterise the polymeric feedstock and analyse the influence of process parameters under three-point bending and quasi-static conditions. Besides, three porcine rib samples were considered as a reference for the development of the artificial bones. Bone surrogates were manufactured from the 3D-scanned real bone geometries. In order to reproduce the trabecular and cortical bone, a lattice structure for the infill and a compact shell surrounding the core were employed. Infill density and shell thickness were evaluated through different printing configurations. Additionally, a computational analysis based on the phase-field approach was conducted to simulate the experimental tests and predict fracture. The modelling considered homogenisation of the infill material. ResultsOutcomes demonstrated the potential of the presented methodology. Maximum force and flexural stiffness were compared to real bone properties to find the optimal printing configuration, replicating the flexural mechanical behaviour of bone tissue. Certain configurations accurately reproduce the studied properties. Regarding the numerical model, strength and stiffness prediction was validated with experimental results. ConclusionsThe presented methodology enables the manufacturing of artificial bones with accurate geometries and tailored mechanical properties. Furthermore, the described modelling strategy offers a powerful tool for designing bone surrogates.

Functional modularity and mechanical stress shape plastic responses during fish development.

The adaptive potential of plastic phenotypes relies on combined developmental responses. We investigated how manipulation of developmental conditions related to foraging mode in the fish Megaleporinus macrocephalus induces plastic responses at different levels: (a) functional modularity of skull bones, (b) biomechanical properties of the chondrocranium using finite element models, (c) bmp4 expression levels, used as a proxy for molecular pathways involved in bone responses to mechanical load. We identified new modules in experimental groups, suggesting increased integration in specific head bone elements associated with the development of subterminal and upturned mouths, which are major features of Megaleporinus plastic morphotypes released in the lab. Plastic responses in head shape involved differences in the magnitude of mechanical stress, which seem restricted to certain chondrocranium regions. Three bones represent a "mechanical unit" related to changes in mouth position induced by foraging mode, suggesting that functional modularity might be enhanced by the way specific regions respond to mechanical load. Differences in bmp4 expression levels between plastic morphotypes indicate associations between molecular signaling pathways and biomechanical responses to load. Our results offer a multilevel perspective of epigenetic factors involved in plastic responses, expanding our knowledge about mechanisms of developmental plasticity that originate novel complex phenotypes.

The Effect of Implant Length and Bone Quality on the Biomechanical Responses of Dental Implant and Surrounding Bone – A Three-Dimensional Finite Element Analysis

The robustness of dental implant systems in the context of occlusal restoration relies significantly on biomechanical factors associated with the imposition of excessive loads. These factors encompass the macro geometries of the implants, bone qualities, parafunctional oral habits, and specific materials employed. The choice of different implant lengths in different bone qualities may give rise to distinct effects on the way loads are distributed across the interface between the implant and the adjacent bone. As of now, the influence of implant length and bone quality on the surrounding tissues and the stability of implant structure continues to be a matter of debate and uncertainty, particularly in situations involving the possibility of implant failure. This study employed three-dimensional finite element analysis to investigate five distinct implant lengths (4, 6, 10, 13, and 15 mm) in two types of bone quality (type II and III). The bone tissues were characterized through the utilization of computed tomography image datasets and then underwent processing within the SolidWorks software. All geometric configurations were transformed into finite element models, which were subjected to analysis within the ANSYS software. Anisotropic and isotropic properties were attributed to the bone and implant models, respectively. A dynamic occlusal loading quantified at 300 N was applied to the implant body, accompanied by a pre-tension force of 20 N on the screw component. The longer implants exhibited decreased stress magnitudes in type II bone (87.86 – 36.66 MPa) and increased stress magnitudes in type III bone (80.5 – 2128.9 MPa) within the surrounding bone tissue, in comparison to the shorter implants. However, stress within the implant body was generally elevated with the use of longer implants in both bone types (type II: 505.32 – 625.35 MPa; type III: 500.45 – 2186.7 MPa). Irrespective of bone quality, the longer implants predominantly led to lower bone strain levels (type II: 0.006828 – 0.003328; type III: 0.054250 – 0.021678) and overall deformation of the implant-abutment assembly (type II: 0.1458 – 0.1348 μm; type III: 0.1754 – 0.1492 μm) compared to their shorter counterparts. Among all the assessed findings, type III bone displayed a more pronounced adverse impact on the biomechanical responses of the dental implant and neighbouring bone except for the implant stresses under the applied physiological loading.