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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 -
BioMed Research International 2022This study was conducted to better understand the specific behavior of the intraosseous fluid flow. We calculated the number and distribution of bone canaliculi around...
This study was conducted to better understand the specific behavior of the intraosseous fluid flow. We calculated the number and distribution of bone canaliculi around the osteocytes based on the varying shapes of osteocytes. We then used these calculated parameters and other bone microstructure data to estimate the anisotropy permeability of the lacunar-canalicular network. Poroelastic finite element models of the osteon were established, and the influence of the osteocyte shape on the fluid flow properties of osteons under an axial displacement load was analyzed. Two types of boundary conditions (BC) that might occur in physiological environments were considered on the cement line of the osteon. BC1 allows free fluid passage from the outer elastic restraint boundary, and BC2 is impermeable and allows no free fluid passage from outer displacement constrained boundary. They both have the same inner boundary conditions that allow fluid to pass through. Changes in the osteocyte shape altered the maximum value of pressure gradient (PG), pore pressure (PP), fluid velocity (FV), and fluid shear stress (FSS) relative to the reference model (spherical osteocytes). The maximum PG, PP, FV, and FSS in BC2 were nearly 100% larger than those in BC1, respectively. It is found that the BC1 was closer to the real physiological environment. The fluid flow along different directions in the elongated osteocyte model was more evident than that in other models, which may have been due to the large difference in permeability along different directions. Changes in osteocyte shape significantly affect the degrees of anisotropy of fluid flow and porous media of the osteon. The model presented in this study can accurately quantify fluid flow in the lacunar-canalicular network.
Topics: Bone and Bones; Haversian System; Osteocytes; Porosity; Stress, Mechanical
PubMed: 35677099
DOI: 10.1155/2022/3935803 -
Bone Reports Jun 2022Antlers are paired deciduous bony cranial appendages of deer that undergo a regular cycle of growth, death and casting, and constitute the most rapidly growing bones in...
Antlers are paired deciduous bony cranial appendages of deer that undergo a regular cycle of growth, death and casting, and constitute the most rapidly growing bones in mammals. Antler growth occurs in an appositional mode and involves a modified form of endochondral ossification. In endochondral bones, calcified cartilage is typically a transient tissue that is eventually completely replaced by bone tissue. We studied the distribution and characteristics of calcified cartilage in hard antlers from three deer species (, , ), i.e., in antlers from which the skin (velvet) had been shed. Remnants of calcified cartilage were regularly present as part of the trabecular framework in the late formed, distal antler portions in all three species, whereas this tissue was largely or completely missing in the more proximal antler portions. The presence of calcified cartilage remnants in the distal antler portions is attributed to the limited antler lifespan of only a few months, which is also the reason for the virtual lack of bone remodeling in antlers. The calcified cartilage matrix was more highly mineralized than the antler bone matrix. Mineralized deposits were observed in some chondrocyte lacunae and occasionally also in osteocyte lacunae, a phenomenon that has not previously been reported in antlers. Using synchrotron radiation-induced X-ray fluorescence (SR-XRF) mapping, we further demonstrated increased zinc concentrations in cement lines, along the inner borders of incompletely formed primary osteons, along the walls of partly or completely mineral-occluded chondrocyte and osteocyte lacunae, and in intralacunar mineralized deposits. The present study demonstrates that antlers are a promising model for studying the mineralization of cartilage and bone matrices and the formation of mineralized deposits in chondrocyte and osteocyte lacunae.
PubMed: 35519288
DOI: 10.1016/j.bonr.2022.101571 -
Journal of the Mechanical Behavior of... Feb 2023The transverse tensile strength of a naturally fallen red deer antler (Cervus Elaphus) was determined through indirect Brazilian tests using dry disc-shape specimens at...
The transverse tensile strength of a naturally fallen red deer antler (Cervus Elaphus) was determined through indirect Brazilian tests using dry disc-shape specimens at quasi-static and high strain rates. Dynamic Brazilian tests were performed in a compression Split-Hopkinson Pressure Bar. Quasi-static tensile and indirect Brazilian tests were also performed along the osteon growth direction for comparison. The quasi-static transverse tensile strength ranged 31.5-44.5 MPa. The strength increased to 83 MPa on the average in the dynamic Brazilian tests, proving a rate sensitive transverse strength. The quasi-static tensile strength in the osteon growth direction was however found comparably higher, 192 MPa. A Weibull analysis indicated a higher tensile ductility in the osteon growth direction than in the transverse to the osteon growth direction. The microscopic analysis of the quasi-static Brazilian test specimens (tensile strain along the osteon growth direction) revealed a micro-cracking mechanism operating by the crack deflection/twisting at the lacunae in the concentric lamellae region and at the interface between concentric lamellae and interstitial lamellae. On the other side, the specimens in the transverse direction fractured in a more brittle manner by the separation/delamination of the concentric lamellae and pulling of the interstitial lamellae. The detected increase in the transverse strength in the high strain rate tests was further ascribed to the pull and fracture of the visco-plastic collagen fibers in the interstitial lamellae. This was also confirmed microscopically; the dynamically tested specimens exhibited flatter fracture surfaces.
Topics: Animals; Haversian System; Antlers; Brazil; Deer; Fractures, Bone
PubMed: 36610280
DOI: 10.1016/j.jmbbm.2023.105648 -
Frontiers in Bioengineering and... 2022Femoral neck fracture (FNF) is the most serious bone disease in the elderly population. The multiscale mechanical response is a key to predicting the strength of the...
Femoral neck fracture (FNF) is the most serious bone disease in the elderly population. The multiscale mechanical response is a key to predicting the strength of the femoral neck, assessing the risk of FNF, and exploring the role of mechanosensation and mechanotransmission in bone remodeling, especially in the context of aging bone. Multiscale finite element (FE) models of the proximal femur for both young and elderly people were developed. The models included organ scale (proximal femur), tissue scale (cortical bone), tissue element scale (osteon), and cell scale [osteocyte lacuna-canalicular network (LCN) and extracellular matrix (ECM), OLCEM]. The mechanical responses of cortical bone and osteocytes in the mid-femoral neck and the differences in mechanical responses between these two scales were investigated. The mechanical responses of cortical bone and osteocyte showed significant differences between the elderly and the young. The minimum principal strains and mean SEDs of cortical bone in the elderly were 2.067-4.708 times and 3.093-14.385 times of the values in the young, respectively; the minimum principal strains and mean SEDs of osteocyte in the elderly were 1.497-3.246 times and 3.044-12 times of the values in the young, respectively; the amplification factors of minimum principal strain in the inferior (Inf), anterior (Ant), and posterior (Post) quadrants in the young were 1.241-1.804 times of the values in the elderly, but the amplification factor of minimum principal strain in the superior (Sup) quadrant was 87.4% of the value in the elderly; the amplification factors of mean SED in the young were 1.124-9.637 times of the values in the elderly. The mass and bone mineral density (BMD) of cortical bone in the femoral neck is closely related to the mechanical response of osteocytes, which provides a new idea for improving cortical bone quality. Perhaps cortical bone quality could be improved by stimulating osteocytes. Quadrantal differences of bone quality in the mid-femoral neck should be considered to improve fracture risk prediction in the future.
PubMed: 35600894
DOI: 10.3389/fbioe.2022.893337 -
Journal of the Mechanical Behavior of... Sep 2023This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To...
This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers, which represented osteons and interstitial tissue, loaded in uniaxial tension. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber "families." Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created by modeling aging via the following changes to the input parameters: (i) increasing porosity from 5% to 15%, (ii) increasing the ratio of the number of osteon fibers relative to interstitial fibers from 40% to 50%, and (iii) changing the fiber material properties from representing mature bone samples to representing elderly bone samples (i.e., increased strength and decreased toughness of interstitial fibers together with decreased toughness of osteon fibers). To understand the respective contributions of these changes, additional models isolating one or two of each of these were also created. From the computed stress-strain curve for the fiber bundle, the yield point (ϵ, σ), ultimate point (ϵ, σ), and toughness (U) for the bundle as a whole were measured. We found that changes to all three input parameters were required for the model to capture the aging-related decline in cortical bone mechanical properties consistent with those previously reported in the literature. In both mature and elderly bundles, rupture of the interstitial fibers drove the initial loss of strength following the ultimate point. Plasticity and more gradual rupture of the osteons drove the remainder of the response. Both the onset and completion of interstitial fiber rupture occurred at lower strains in the elderly vs. mature case. These findings point to the importance of studying microstructural changes beyond porosity, such as the area fraction of osteons and the material properties of osteon and interstitial tissue, in order to further understanding of aging-related changes in bone.
Topics: Humans; Aged; Porosity; Bone and Bones; Cortical Bone; Aging; Models, Theoretical; Haversian System
PubMed: 37499524
DOI: 10.1016/j.jmbbm.2023.106029 -
Journal of Bone and Mineral Metabolism May 2020The composite nature of bone as a material governs its structure and mechanical behavior. How the collagenous matrix mineralizes, in terms of both mineral deposition and...
INTRODUCTION
The composite nature of bone as a material governs its structure and mechanical behavior. How the collagenous matrix mineralizes, in terms of both mineral deposition and structure of the mineral crystals, is highly interesting when trying to elucidate the complex structural changes that occur during bone growth and maturation. We have previously looked at mineral deposition and structural evolution of the collagenous matrix, linking both to changes in mechanics. The purpose of this study was to provide specific information on changes in crystal size and organization as a function of growth and maturation.
MATERIALS AND METHODS
Using micro-computed tomography (µCT) and micro-focused scanning small-angle X-ray scattering (SAXS) we investigated cortical bone in two orthogonal directions relative to the long axis of the humeri of New Zealand White rabbits spanning from new-born to 6-months of age. We also investigated the changes with tissue age by looking at radial profiles of osteonal structures in the 6-months old rabbits. The findings were compared to our previous compositional, structural and mechanical data on the same sample cohort.
RESULTS
µCT showed a continuous mineral deposition up until 3-months of age, whilst the SAXS data showed an increase in both crystal thickness and degree of orientation up until 6-months of age. The osteonal profiles showed no statistically significant changes in crystal thickness.
CONCLUSIONS
Comparison to previously collected mechanical data suggests that changes are not only explained by amount of mineral in the tissue but also by the crystal dimensions.
Topics: Aging; Animals; Bone Density; Calcification, Physiologic; Cortical Bone; Female; Imaging, Three-Dimensional; Rabbits; Scattering, Small Angle; X-Ray Microtomography
PubMed: 31807903
DOI: 10.1007/s00774-019-01068-y -
Ultrasound in Medicine & Biology Mar 2021The goal of this study was to evaluate whether ultrasonic velocities in cortical bone can be considered as a proxy for mechanical quality of cortical bone tissue...
The goal of this study was to evaluate whether ultrasonic velocities in cortical bone can be considered as a proxy for mechanical quality of cortical bone tissue reflected by porosity and compression strength. Micro-computed tomography, compression mechanical testing and resonant ultrasound spectroscopy were used to assess, respectively, porosity, strength and velocity of bulk waves of both shear and longitudinal polarisations propagating along and perpendicular to osteons, in 92 cortical bone specimens from tibia and femur of elderly human donors. All velocities were significantly associated with strength (r = 0.65-0.83) and porosity (r = -0.64 to -0.77). Roughly, according to linear regression models, a decrease in velocity of 100 m/s corresponded to a loss of 20 MPa in strength (which is approximately 10% of the largest strength value) and to an increase in porosity of 5%. These results provide a rationale for the in vivo measurement of one or several velocities for the diagnosis of bone fragility.
Topics: Aged; Aged, 80 and over; Compressive Strength; Cortical Bone; Female; Femur; Humans; Male; Porosity; Tibia; Ultrasonic Waves
PubMed: 33341302
DOI: 10.1016/j.ultrasmedbio.2020.11.012 -
Biology Apr 2023Cortical bone microstructure assessment in biological and forensic anthropology can assist with the estimation of age-at-death and animal-human differentiation, for...
Cortical bone microstructure assessment in biological and forensic anthropology can assist with the estimation of age-at-death and animal-human differentiation, for example. Osteonal structures within cortical bone are the key feature under analysis, with osteon frequency and metric parameters providing crucial information for the assessment. Currently, the histomorphological assessment consists of a time-consuming manual process for which specific training is required. Our work investigates the feasibility of automatic analysis of human bone microstructure images through the application of deep learning. In this paper, we use a U-Net architecture to address the semantic segmentation of such images into three classes: intact osteons, fragmentary osteons, and background. Data augmentation was used to avoid overfitting. We evaluated our fully automatic approach using a sample of 99 microphotographs. The contours of intact and fragmentary osteons were traced manually to provide ground truth. The Dice coefficients were 0.73 for intact osteons, 0.38 for fragmented osteons, and 0.81 for background, giving an average of 0.64. The Dice coefficient of the binary classification osteon-background was 0.82. Although further refinement of the initial model and tests with larger datasets are needed, this study provides, to the best of our knowledge, the first proof of concept for the use of computer vision and deep learning for differentiating both intact and fragmentary osteons in human cortical bone. This approach has the potential to widen and facilitate the use of histomorphological assessment in the biological and forensic anthropology communities.
PubMed: 37106819
DOI: 10.3390/biology12040619 -
Knee Surgery, Sports Traumatology,... Apr 2024The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert...
PURPOSE
The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert opinion to improve indications, decision-making and administration-related aspects when using blood-derived orthobiologics (for simplicity indicated as PRP-platelet-rich plasma-with PRP being the most common product) for the management of knee osteoarthritis (OA).
METHODS
Leading European expert clinicians and scientists were divided into a steering group, a rating group and a peer review group. The steering group prepared 28 question-statement sets divided into three sections: PRP rationale and indications, PRP preparation and characterisation and PRP protocol. The quality of the statements received grades of recommendation ranging from A (high-level scientific support) to B (scientific presumption), C (low-level scientific support) or D (expert opinion). The question-statement sets were then evaluated by the rating group, and the statements scored from 1 to 9 based on their degree of agreement with the statements produced by the steering group. Once a general consensus was reached between the steering and rating groups, the document was submitted to the peer review group who evaluated the geographic adaptability and approved the document. A final combined meeting of all the members of the consensus was held to produce the official document.
RESULTS
The literature review on the use of blood-derived products for knee OA revealed that 9 of 28 questions/statements had the support of high-level scientific literature, while the other 19 were supported by a medium-low scientific quality. Three of the 28 recommendations were grade A recommendations: (1) There is enough preclinical and clinical evidence to support the use of PRP in knee OA. This recommendation was considered appropriate with a strong agreement (mean: 8). (2) Clinical evidence has shown the effectiveness of PRP in patients for mild to moderate degrees of knee OA (KL ≤ 3). This recommendation was considered appropriate with a strong agreement (mean: 8.1). (3) PRP injections have been shown to provide a longer effect in comparison to the short-term effect of CS injections. They also seem to provide a safer use profile with less potential related complications. This recommendation was considered appropriate with a very strong agreement (mean: 8.7). Six statements were grade B recommendations, 7 were grade C and 12 were grade D. The mean rating score was 8.2 ± 0.3.
CONCLUSIONS
The consensus group reached a high level of agreement on all the questions/statements despite the lack of clear evidence for some questions. According to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first-line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1-3.
LEVEL OF EVIDENCE
Level II.
Topics: Humans; Osteoarthritis, Knee; Consensus; Platelet-Rich Plasma; Arthroscopy; Treatment Outcome; Injections, Intra-Articular
PubMed: 38436492
DOI: 10.1002/ksa.12077