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Journal of the Mechanical Behavior of... Nov 2022Severe bone fractures are often treated by appending internal fixations. In unhealthy or osteoporotic patients, post-implantation bone fractures can occur due to...
Severe bone fractures are often treated by appending internal fixations. In unhealthy or osteoporotic patients, post-implantation bone fractures can occur due to external impact (e.g. from a fall), day-to-day activities in highly-osteoporotic cases and mismatches in the stiffness of bone and the implant's biomaterial, since this causes stress concentrations. One approach to alleviating this problem is to use biomaterials that closely mimic the effective stiffness of real bone, thereby more seamlessly integrating the fixation. This requires to know the properties target (bone properties) and therefore, it highlights the relevance of the evaluation of the bone's mechanical properties which is impractical via direct measurement. This work presents a methodology (multistage homogenisation) for predicting the anisotropic stiffness of bone given the porosity and mineral fraction, both of which are more readily obtained than the mechanical properties themselves. Unlike previous work we: (i) account for finger-like morphology of the mineral phase at the nanoscale; (ii) use microscopy data to model the osteon geometry and its curvilinear anisotropy at the microscale, and (iii) use data to define the trabecular (microCT) and cortical (microscopy) bone geometries at the mesoscale. The predicts have been shown to agree favourably with experimental data in the literature as well as previous modelling works. The results are summarised in a database containing anisotropic stiffness tensors applicable to a broad range of degrees of bone health (e.g. mineral fractions and mesoscale porosities); thus, this work is a contribution towards being able to design more robust patient-specific bone implants in practice.
Topics: Biocompatible Materials; Bone and Bones; Fractures, Bone; Humans; Osteoporosis; X-Ray Microtomography
PubMed: 36084417
DOI: 10.1016/j.jmbbm.2022.105431 -
Methods and Protocols May 2022Raman spectroscopy has recently been used for quantitative analyses of cortical bone tissue and related materials, such as dentin and enamel. While those analyses have...
Raman spectroscopy has recently been used for quantitative analyses of cortical bone tissue and related materials, such as dentin and enamel. While those analyses have proven useful as potential diagnostic tools, the Raman spectrum of bone encrypts a wealth of additional molecular scale details about structure and crystal arrangement, which are yet to be unfolded. Such details directly link to both bone physiology and pathology. In this work, a triple monochromator spectrometer with high spectral resolution, employed in polarized light configurations, was used to extract quantitative details about the preferential crystallographic orientation of apatite and collagen components in a human proximal femoral cortical bone sample. This body of information was then used to model the bone structure at the nanometric scale through a methodology that could be key in assessments of bone structure in health and disease.
PubMed: 35645349
DOI: 10.3390/mps5030041 -
Medical & Biological Engineering &... Mar 2020Irreversible osteoporosis may occur in astronauts during long-term space flight. The flow field of tissue fluid in the lacunar-canalicular system (LCS) of osteon and the...
Irreversible osteoporosis may occur in astronauts during long-term space flight. The flow field of tissue fluid in the lacunar-canalicular system (LCS) of osteon and the mechanical response of osteocytes to the flow field under different gravity fields were studied by numerical simulation. This study is expected to explain how the decrease in liquid transmission within microgravity can be a cause of osteoporosis in astronauts from the perspective of biomechanics using a fundamental research approach. A 3D axisymmetric fluid-solid coupling finite element model of an osteon with a two-stage pore structure (Haversian canals and lacunar-canalicular network) and osteocytes was established. The model compared the influence of differences in pulsating pressure of arterioles in Haversian canal, from 33 mmHg to 45 mmHg within a microgravity field (0 g), Earth's gravity field (1 g), and a high G gravitational fields (2-8 g). The liquid flow velocity in the LCS within a microgravity field was less than that within a normal gravitational field, and the flow velocity increased with gravitational acceleration. There was a significant liquid pressure gradient in the osteocytes within a normal and higher gravitational field compared with in microgravity. A reduction in the fluid flow velocity and fluid shear stress on osteocytes in different zones in microgravity compared with Earth's gravitational field. For these reasons, possibly causing a decrease in mechanical conduction and biochemical function, even cell death, leads to increased osteoclast activity, eventually causing the loss of a large quantity of bone. Graphical abstract A 3D axisymmetric fluid-solid coupling finite element model of an osteon with a two-stage pore structure was established. The model compared the influence of magnitudes of gravity on liquid transmission in LCS and mechanical response of osteocytes. The mean flow velocity of liquid in various layers (shallow, middle, and deep) increased linearly as acceleration due to gravity increased, and there was a significant liquid pressure gradient in osteocytes within a normal gravitational field compared with in microgravity. In microgravity environment, the osteocytes were unable to experience the pressure difference compared to that of Earth, possibly causing a decrease in mechanical conduction and biochemical function, even cell death, leading to increased osteoclast activity, eventually causing the loss of a large quantity of bone.
Topics: Computer Simulation; Finite Element Analysis; Gravitation; Haversian System; Humans; Numerical Analysis, Computer-Assisted; Osteocytes; Pressure; Rheology; Stress, Mechanical; Weightlessness
PubMed: 31900816
DOI: 10.1007/s11517-019-02108-5 -
International Journal of Molecular... Mar 2023The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural...
The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural material composites. This study examines the in vitro osteo regenerative potential of polycaprolactone (PCL) tissue scaffolding, fabricated via a three-dimensional (3D) additive manufacturing technology, i.e., a pneumatic micro extrusion (PME) process. The objectives of this study were: (i) To examine the innate osteoinductive and osteoconductive potential of 3D-printed PCL tissue scaffolding and (ii) To perform a direct in vitro comparison of 3D-printed PCL scaffolding with allograft Allowash cancellous bone cubes with regards to cell-scaffold interactions and biocompatibility with three primary human bone marrow (hBM) stem cell lines. This study specifically examined cell survival, cell integration, intra-scaffold cell proliferation, and differentiation of progenitor cells to investigate the potential of 3D-printed PCL scaffolds as an alternative to allograft bone material for the repair of orthopedic injuries. We found that mechanically robust PCL bone scaffolds can be fabricated via the PME process and the resulting material did not elicit detectable cytotoxicity. When the widely used osteogenic model SAOS-2 was cultured in PCL extract medium, no detectable effect was observed on cell viability or proliferation with multiple test groups showing viability ranges of 92.2% to 100% relative to a control group with a standard deviation of ±10%. In addition, we found that the honeycomb infill pattern of the 3D-printed PCL scaffold allowed for superior mesenchymal stem-cell integration, proliferation, and biomass increase. When healthy and active primary hBM cell lines, having documented in vitro growth rates with doubling times of 23.9, 24.67, and 30.94 h, were cultured directly into 3D-printed PCL scaffolds, impressive biomass increase values were observed. It was found that the PCL scaffolding material allowed for biomass increase values of 17.17%, 17.14%, and 18.18%, compared to values of 4.29% for allograph material cultured under identical parameters. It was also found that the honeycomb scaffold infill pattern was superior to the cubic and rectangular matrix structures, and provided a superior microenvironment for osteogenic and hematopoietic progenitor cell activity and auto-differentiation of primary hBM stem cells. Histological and immunohistochemical studies performed in this work confirmed the regenerative potential of PCL matrices in the orthopedic setting by displaying the integration, self-organization, and auto-differentiation of hBM progenitor cells within the matrix. Differentiation products including mineralization, self-organizing "proto-osteon" structures, and in vitro erythropoiesis were observed in conjunction with the documented expression of expected bone marrow differentiative markers including CD-99 (>70%), CD-71 (>60%), and CD-61 (>5%). All of the studies were conducted without the addition of any exogenous chemical or hormonal stimulation and exclusively utilized the abiotic and inert material polycaprolactone; setting this work apart from the vast majority of contemporary investigations into synthetic bone scaffold fabrication In summary, this study demonstrates the unique clinical potential of 3D-printed PCL scaffolds for stem cell expansion and incorporation into advanced microstructures created via PME manufacturing to generate a physiologically inert temporary bony defect graft with significant autograft features for enhanced end-stage healing.
Topics: Humans; Bone Marrow Cells; Caproates; Osteogenesis; Polyesters; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds; Mesenchymal Stem Cells
PubMed: 36902373
DOI: 10.3390/ijms24054940 -
Journal of Biomechanics Nov 2020The microstructure of cortical bone is key for the tissue's high toughness and strength and efficient toughening mechanisms have been identified at the microscale, for...
The microstructure of cortical bone is key for the tissue's high toughness and strength and efficient toughening mechanisms have been identified at the microscale, for example when propagating cracks interact with the osteonal microstructure. Finite element models have been proposed as suitable tools for analyzing the complex link between the local tissue structure and the fracture resistance of cortical bone. However, previous models that could capture realistic crack paths in cortical bone were due to the required computational effort limited to idealized osteon geometries and small (<1 mm) model domains. The objective of this study was therefore to bridge the gap between experimental and numerical analysis of crack propagation in cortical bone by introducing image-based models at the mesoscale. Tissue orientation maps from high-resolution micro-CT images were used to define the distribution and orientation of weak interfaces in the models. Crack propagation was simulated using the extended finite element method in combination with an interface damage model, previously developed to simulate crack propagation in microstructural osteon models. The results showed that image-based mesoscale models can be used to capture interactions between cracks and microstructure. The simulated crack paths predicted the general trends seen in experiments with more irregular patterns for cracks propagating perpendicular compared to parallel to the osteon orientation. In all, the proposed method enabled an efficient description of the tissue level microstructure, which is a necessity to predict realistic crack paths in cortical bone and is an important step towards simulating crack propagation in bone models in 3D.
Topics: Bone and Bones; Cortical Bone; Fractures, Bone; Haversian System; Humans; Models, Biological; Stress, Mechanical
PubMed: 32980752
DOI: 10.1016/j.jbiomech.2020.110020 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: To study the role and place of bone grafting in the formation of bone stump after amputation.
OBJECTIVE
The aim: To study the role and place of bone grafting in the formation of bone stump after amputation.
PATIENTS AND METHODS
Materials and methods: 3 series of experiments were carried out on 44 rabbits with amputation of the thigh in the middle third and stump grafting using osteoplastic hermetic closure of the canal with a thin cortical plate (series I), closure of the canal with a spongy bone (series II), and loose closure of the canal with a cortical graft located at the entrance to the canal at an angle of 30° (ІІІ series). Observation period: 1, 3, 6 months. Histological examination method with vascular filling with 10% mascara-gelatin mixture.
RESULTS
Results: In series I, in the majority of observations, a stump of a cylindrical shape with a bone locking plate of an osteon-beam structure and normalization of intraosseous microcirculation was formed. A slight displacement of the graft caused a violation of microcirculation. In series II, organotypic stumps were formed in all observations. In series III, incomplete closure of the bone marrow cavity led to sharp microcirculatory disorders and the course of the reparative process with pathological bone remodeling.
CONCLUSION
Conclusions: The parameters of the favorable course of the reparative process and the formation of the organotypic bone stump are the safety of its cylindrical shape, the presence of a compact bone structure, normalization of intraosseous microcirculation.
Topics: Amputation, Surgical; Amputation Stumps; Animals; Filing; Microcirculation; Rabbits; Thigh
PubMed: 33813442
DOI: No ID Found -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2021Mammalian feeding behaviors are altered when mechanically challenging (e.g., tough, stiff) foods require large bite forces or prolonged mastication. Bony responses to...
Mammalian feeding behaviors are altered when mechanically challenging (e.g., tough, stiff) foods require large bite forces or prolonged mastication. Bony responses to high bite forces are well-documented for the mammalian skull, but osteogenesis due to cyclical loading, caused by repetitive chewing, is more poorly understood. Previous studies demonstrate that cyclical loading results in greater bone formation in the rabbit masticatory apparatus and in substantial Haversian remodeling in primate postcrania. Here we assess the relationship between cyclical loading and remodeling in the rabbit maxilla. Twenty male New Zealand white rabbits (Oryctolagus cuniculus) were raised on either an overuse or control diet (10 per group) for 48 weeks, beginning at weaning onset. The control group was raised on a diet of rabbit pellets (E = 29 MPa, R = 1031 J/m ), whereas the overuse group ate rabbit pellets and hay, which has high stiffness (E = 3336 MPa) and toughness (R = 2760 J/m ) properties. Hay requires greater chewing investment (475 chews/g) and longer chewing durations (568 s/g) than pellets (161 chews/g and 173 s/g), therefore causing cyclical loading of the jaws. Remodeling was measured as osteon population density (OPD), percent Haversian bone (%HAV), and osteon cross-sectional area (On.Ar). The only significant difference found was greater On.Ar in the alveolar region of the maxilla (p < 0.001) in the overuse group. The hypothesis that cyclical loading engenders Haversian remodeling in the developing maxilla is not supported. The continuation of modeling throughout the experimental duration may negate the need for remodeling as newly laid bone tends to be more compliant and resistant to crack propagation.
Topics: Animals; Bone Remodeling; Haversian System; Male; Mastication; Maxilla; Rabbits; Skull
PubMed: 33586861
DOI: 10.1002/ar.24599 -
International Journal of Legal Medicine Nov 2019Various methods are available for estimating age from skeletal remains, amongst them the use of histomorphometry. It is generally argued that age estimation standards...
Various methods are available for estimating age from skeletal remains, amongst them the use of histomorphometry. It is generally argued that age estimation standards are population specific, but this in itself creates problems as the reference samples used are often not large enough and/or lack substantial representation of all age cohorts. Traditional age methods have been shown to suffer from problems such as age mimicry. This paper aims at establishing histological age-at-death standards for the white South African population by supplementing the available sample (lacking an adequate number of young adults) with another sample of European descent to avoid over-estimation of age in younger individuals caused by age mimicry. Bone microstructures related to the number of osteons and fragments, osteon size and Haversian canal size that change with advancing age were used for the development of regression formulae. A histomorphometric assessment of the anterior cortex of the femur was done using stereology for the estimation of age at death. All sections were analysed using the optical fractionator and nucleator probes. A sample of 94 bone sections (n = 50 male, n = 44 females) of white South African individuals were used. A sample of Danish individuals (n = 14 males, n = 16 females) was combined with the South African sample to create a normal age distribution for the reference sample. Single and multiple regression equations were developed after randomly selecting a hold-out sample (n = 14) for validation. Osteon size (average length, surface area and volume) showed the highest correlation with age, followed by the number of osteons and fragments per grid area. Haversian canal size showed inconsistent changes with advancing age. Using the regression equations, predicted ages were obtained for the 14 individuals. RMSE values ranged between 14 and 17 years, which we deemed acceptable.
Topics: Adolescent; Adult; Age Determination by Skeleton; Aged; Aged, 80 and over; Female; Femur; Forensic Anthropology; Haversian System; Humans; Male; Middle Aged; Optical Imaging; Regression Analysis; South Africa; White People; Young Adult
PubMed: 31468135
DOI: 10.1007/s00414-019-02152-8 -
Journal of Biomedical Materials... May 2022The crosstalk between osteoblasts and endothelial cells is critical for bone vascularization and regeneration. Here, we used a coaxial 3D bioprinting method to directly...
The crosstalk between osteoblasts and endothelial cells is critical for bone vascularization and regeneration. Here, we used a coaxial 3D bioprinting method to directly print an osteon-like structure by depositing angiogenic and osteogenic bioinks from the core and shell regions of the coaxial nozzle, respectively. The bioinks were made up of gelatin, gelatin methacryloyl (GelMA), alginate, and hydroxyapatite (HAp) nanoparticles and were loaded with human umbilical vascular endothelial cells (HUVECs) and osteoblasts (MC3T3) in the core and shell regions, respectively. Conventional monoaxial 3D bioprinting was used as a control method, where the hydrogels, HAp nanoparticles, MC3T3 cells, and HUVECs were all mixed in one bioink and printed from the core nozzle. As a result, the bioprinted scaffolds were composed of cell-laden fibers with either a core-shell or homogenous structure, providing a non-contact (indirect) or contact (direct) co-culture of MC3T3 cells and HUVECs, respectively. Both structures supported the 3D culture of HUVECs and osteoblasts over a long period. The scaffolds also supported the expression of osteogenic and angiogenic factors. However, the gene expression was significantly higher for the core-shell structure than the homogeneous structure due to the well-defined distribution of osteoblasts and endothelial cells and the formation of vessel-like structures in the co-culture system. Our results indicated that the coaxial bioprinting technique, with the ability to create a non-contact co-culture of cells, can provide a more efficient bioprinting strategy for printing highly vascularized and bioactive bone structures.
Topics: Bioprinting; Coculture Techniques; Endothelial Cells; Gelatin; Humans; Hydrogels; Methacrylates; Polymers; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 35025130
DOI: 10.1002/jbm.a.37354 -
Frontiers in Bioengineering and... 2021The regeneration of load-bearing segmental bone defects remains a significant clinical problem in orthopedics, mainly due to the lack of scaffolds with composition and...
The regeneration of load-bearing segmental bone defects remains a significant clinical problem in orthopedics, mainly due to the lack of scaffolds with composition and 3D porous structure effective in guiding and sustaining new bone formation and vascularization in large bone defects. In the present study, biomorphic calcium phosphate bone scaffolds (GreenBone™) featuring osteon-mimicking, hierarchically organized, 3D porous structure and lamellar nano-architecture were implanted in a critical cortical defect in sheep and compared with allograft. Two different types of scaffolds were tested: one made of ion-doped hydroxyapatite/β-tricalcium-phosphate (GB-1) and other made of undoped hydroxyapatite only (GB-2). X-ray diffraction patterns of GB-1 and GB-2 confirmed that both scaffolds were made of hydroxyapatite, with a minor amount of β-TCP in GB-1. The chemical composition analysis, obtained by ICP-OES spectrometer, highlighted the carbonation extent and the presence of small amounts of Mg and Sr as doping ions in GB-1. SEM micrographs showed the channel-like wide open porosity of the biomorphic scaffolds and the typical architecture of internal channel walls, characterized by a cell structure mimicking the natural parenchyma of the rattan wood used as a template for the scaffold fabrication. Both GB-1 and GB-2 scaffolds show very similar porosity extent and 3D organization, as also revealed by mercury intrusion porosimetry. Comparing the two scaffolds, GB-1 showed slightly higher fracture strength, as well as improved stability at the stress plateau. In comparison to allograft, at the follow-up time of 6 months, both GB-1 and GB-2 scaffolds showed higher new bone formation and quality of regenerated bone (trabecular thickness, number, and separation). In addition, higher osteoid surface (OS/BS), osteoid thickness (OS.Th), osteoblast surface (Ob.S/BS), vessels/microvessels numbers, as well as substantial osteoclast-mediated implant resorption were observed. The highest values in OS.Th and Ob. S/BS parameters were found in GB-1 scaffold. Finally, Bone Mineralization Index of new bone within scaffolds, as determined by micro-indentation, showed a significantly higher microhardness for GB-1 scaffold in comparison to GB-2. These findings suggested that the biomorphic calcium phosphate scaffolds were able to promote regeneration of load-bearing segmental bone defects in a clinically relevant scenario, which still represents one of the greatest challenges in orthopedics nowadays.
PubMed: 34646817
DOI: 10.3389/fbioe.2021.734486