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Frontiers in Bioengineering and... 2022The Haversian system is one of the most important pathways to repair bone defects, and it is the basic guarantee for the repair of bone defects, which means that the...
The Haversian system is one of the most important pathways to repair bone defects, and it is the basic guarantee for the repair of bone defects, which means that the formation of the Haversian system indicates repairing of the defects. The integration of structure and function for tissue engineering scaffolds is of great importance in mimicking native bone tissue. However, in contrast to the increasing demands, how to rapidly prepare various sizes of such Haversian system mimicking scaffolds in batch becomes a major challenge. In this study, we designed three types of platforms with different sizes in combination with the freeze-drying approach. Chitosan/type I collagen composite materials were used to study the structure, morphology, and performance of the production, and the effects of the controlled architecture on osteogenesis. Results showed that the physicochemical effects of the mass fabricated scaffolds of various sizes met the requirements of bone repair materials. In addition, the scaffolds had good cytocompatibility and excellent bone repair performance, which have potential clinical applications.
PubMed: 36304903
DOI: 10.3389/fbioe.2022.1013528 -
Bone Reports Dec 2022The differences in bone nanomechanical properties between cortical (Ct) and trabecular (Tb) bone remain uncertain, whereas knowing the respective contribution of each...
The differences in bone nanomechanical properties between cortical (Ct) and trabecular (Tb) bone remain uncertain, whereas knowing the respective contribution of each compartment is critical to understand the origin of bone strength. Our purpose was to compare bone mechanical and intrinsic properties of Ct and Tb compartments, at the bone structural unit (BSU) level, in iliac bone taken from a homogeneous untreated human population. Among 60 PMMA-embedded transiliac bone biopsies from untreated postmenopausal osteoporotic women (64 ± 7 year-old), >2000 BSUs were analysed by nanoindentation in physiological wet conditions [indentation modulus (elasticity), hardness, dissipated energy], by Fourier transform infrared (FTIRM) and Raman microspectroscopy (mineral and organic characteristics), and by X-ray microradiography (degree of mineralization of bone, DMB). BSUs were categorized based on tissue age, osteonal (Ost) and interstitial (Int) tissues location and bone compartments (Ct and Tb). Indentation modulus was higher in Ct than in Tb BSUs, both in Ost and Int. dissipated energy was higher in Ct than Tb, in Int BSUs. Hardness was not different between Ct and Tb BSUs. In Ost or Int BSUs, mineral maturity (conversion of non-apatitic into apatitic phosphates) was higher in Ct than in Tb, as well as for collagen maturity (Ost). Mineral content assessed as mineral/matrix (FTIRM and Raman) or as DMB, was lower in Ct than in Tb. Crystallinity (FTIRM) was similar in BSUs from Ct and Tb, and slightly lower in Ct than in Tb when measured by Raman, indicating that the crystal size/perfection was quite similar between Ct and Tb BSUs. The differences found between Ost and Int tissues were much higher than the difference found between Ct and Tb for all those bone material properties. Multiple regression analysis showed that Indentation modulus and dissipated energy were mainly explained by mineral maturity in Ct and by collagen maturity in Tb, and hardness by mineral content in both Ct and Tb. In conclusion, in untreated human iliac bone, Ct and Tb BSUs exhibit different characteristics. Ct BSUs have higher indentation modulus, dissipated energy (Int), mineral and organic maturities than Tb BSUs, without difference in hardness. Although those differences are relatively small compared to those found between Ost and Int BSUs, they may influence bone strength at macroscale.
PubMed: 36213624
DOI: 10.1016/j.bonr.2022.101623 -
Scientific Reports Oct 2022Osteoporosis is an age-related disorder that is characterized by reduced bone mass. Its prevention and treatment are important healthcare issues for maintaining social...
Osteoporosis is an age-related disorder that is characterized by reduced bone mass. Its prevention and treatment are important healthcare issues for maintaining social activity in aged societies. Although bone fractures mostly occur at sites of weakened cortical bone, pathophysiological and pharmacological evaluations of bone mass have tended to be predominantly assessed in trabecular bone. To statistically characterize cortical bone remodeling, we originally established multimode fluorescence imaging and artificial intelligence (AI)-driven morphometric analyses in six-month-old female rabbits with well-defined cortical remodeling, similar to that in humans. We evaluated three distinct administration frequencies of teriparatide [TPTD; human parathyroid hormone, hPTH (1-34)]: once (1/w), twice (2/w), and seven times (7/w) a week, with the same total dose (140 μg/kg/week). Our analyses revealed significant expansions of the osteocytic lacunar-canalicular system and Haversian canals accompanied by the development of cortical porosity and endosteal naïve bone formation induced by a frequent administration regimen (7/w) of TPTD; however, once-weekly (1/w) and twice-weekly (2/w) administration of TPTD showed little effect. These findings demonstrate a clear contrast between the effects of frequent and infrequent administration of TPTD on cortical bone metabolism and suggest that osteocytic bone remodeling is involved in the pharmacological action of PTH.
Topics: Aged; Animals; Artificial Intelligence; Bone Density; Bone Density Conservation Agents; Female; Fluorescence; Humans; Infant; Parathyroid Hormone; Rabbits; Teriparatide
PubMed: 36207444
DOI: 10.1038/s41598-022-20793-5 -
Molecules (Basel, Switzerland) Sep 2022Autologous bone is the gold standard in regeneration processes. However, there is an endless search for alternative materials in bone regeneration. Xenografts can act as... (Comparative Study)
Comparative Study
Autologous bone is the gold standard in regeneration processes. However, there is an endless search for alternative materials in bone regeneration. Xenografts can act as bone substitutes given the difficulty of obtaining bone tissue from patients and before the limitations in the availability of homologous tissue donors. Bone neoformation was studied in critical-size defects created in the parietal bone of 40 adult male Wistar rats, implanted with xenografts composed of particulate bovine hydroxyapatite (HA) and with blocks of bovine hydroxyapatite (HA) and Collagen, which introduces crystallinity to the materials. The Fourier-transform infrared spectroscopy (FTIR) analysis demonstrated the carbonate and phosphate groups of the hydroxyapatite and the amide groups of the collagen structure, while the thermal transitions for HA and HA/collagen composites established mainly dehydration endothermal processes, which increased (from 79 °C to 83 °C) for F2 due to the collagen presence. The xenograft's X-ray powder diffraction (XRD) analysis also revealed the bovine HA crystalline structure, with a prominent peak centered at 32°. We observed macroporosity and mesoporosity in the xenografts from the morphology studies with heterogeneous distribution. The two xenografts induced neoformation in defects of critical size. Histological, histochemical, and scanning electron microscopy (SEM) analyses were performed 30, 60, and 90 days after implantation. The empty defects showed signs of neoformation lower than 30% in the three periods, while the defects implanted with the material showed partial regeneration. InterOss Collagen material temporarily induced osteon formation during the healing process. The results presented here are promising for bone regeneration, demonstrating a beneficial impact in the biomedical field.
Topics: Amides; Animals; Bone Regeneration; Bone Substitutes; Cattle; Collagen; Durapatite; Heterografts; Humans; Male; Rats; Rats, Wistar
PubMed: 36144483
DOI: 10.3390/molecules27185745 -
Nanoscale Advances Aug 2021Hierarchical biological materials, such as osteons and plant cell walls, are complex structures that are difficult to mimic. Here, we combine liquid crystal systems and...
Hierarchical biological materials, such as osteons and plant cell walls, are complex structures that are difficult to mimic. Here, we combine liquid crystal systems and polymerization techniques within confined systems to develop complex structures. A single-domain concentric chiral nematic polymeric fiber was obtained by confining cellulose nanocrystals (CNCs) and hydroxyethyl acrylate inside a capillary tube followed by UV-initiated polymerization. The concentric chiral nematic structure continues uniformly throughout the length of the fiber. The pitch of the chiral nematic structure could be controlled by changing the CNC concentration. We tracked the formation of the concentric structure over time and under different conditions with variation of the tube orientation, CNC concentration, CNC type, and capillary tube size. We show that the inner radius of the capillary tube is important and a single-domain structure was only obtained inside small-diameter tubes. At low CNC concentration, the concentric chiral nematic structure did not completely cover the cross-section of the fiber. The highly ordered structure was studied using imaging techniques and X-ray diffraction, and the mechanical properties and structure of the chiral nematic fiber were compared to a pseudo-nematic fiber. CNC polymeric fibers could become a platform for many applications from photonics to complex hierarchical materials.
PubMed: 36132352
DOI: 10.1039/d1na00425e -
Bone Dec 2022Diabetes mellitus is a metabolic disease affecting bone tissue at different length-scales. Higher fracture risk in diabetic patients is difficult to detect with common...
Diabetes mellitus is a metabolic disease affecting bone tissue at different length-scales. Higher fracture risk in diabetic patients is difficult to detect with common clinical fracture risk assessment due to normal or high bone mineral density in diabetic patients. The observed higher fracture risk despite normal to high areal bone mineral density in diabetic patients points towards impaired bone material quality. Here, we analyze tibial bone from individuals with type 2 diabetes mellitus using a multiscale-approach, which includes clinical and laboratory-based bone quality measures. Tibial cortical bone tissue from individuals with type 2 diabetes mellitus (T2DM) and age-matched healthy controls (n = 15 each) was analyzed with in situ impact indentation, dual energy X-ray absorptiometry (DXA), high resolution peripheral microcomputed tomography (HR-pQCT), micro-computed tomography (microCT), cyclic indentation, quantitative backscattered electron microscopy (qBEI), vibrational spectroscopy (Raman), nanoindentation, and fluorescence spectroscopy. With this approach, a high cortical porosity subgroup of individuals with T2DM was discriminated from two study groups: individuals with T2DM and individuals without T2DM, while both groups were associated with similar cortical porosity quantified by means of microCT. The high porosity T2DM group, but not the T2DM group, showed compromised bone quality expressed by altered cyclic indentation properties (transversal direction) in combination with a higher carbonate-to-amide I ratio in endocortical bone. In addition, in the T2DM group with high cortical porosity group, greater cortical pore diameter was identified with HR-pQCT and lower tissue mineral density using microCT, both compared to T2DM group. Micromechanical analyses of cross-sectioned osteons (longitudinal direction) with cyclic indentation, qBEI, and nanoindentation showed no differences between the three groups. High tibial cortical porosity in T2DM can be linked to locally altered bone material composition. As the tibia is an accessible skeletal site for fracture risk assessment in the clinics (CT, indentation), our findings may contribute to further understanding the site-specific structural and compositional factors forming the basis of bone quality in diabetes mellitus. Refined diagnostic strategies are needed for a comprehensive fracture risk assessment in diabetic bone disease.
Topics: Humans; Tibia; Diabetes Mellitus, Type 2; X-Ray Microtomography; Porosity; Bone Density; Cortical Bone; Bone and Bones; Absorptiometry, Photon; Fractures, Bone; Amides
PubMed: 36113843
DOI: 10.1016/j.bone.2022.116546 -
International Journal of Legal Medicine Jan 2024Timing bone fractures is one of the main tasks of a forensic anthropologist, but still an uncertain diagnostic. In the literature, there are many macroscopic methods to...
Timing bone fractures is one of the main tasks of a forensic anthropologist, but still an uncertain diagnostic. In the literature, there are many macroscopic methods to distinguish perimortem from postmortem fractures, based on the distinct structural and mechanical properties of fresh and dry bones. However, this differentiation is still challenging, in particular when the bones are fragmented or still exhibit fresh properties. Although histologic analysis is often used as a complementary diagnostic tool in forensic pathology, its application in the evaluation of bone fractures is uncommon. The aim of this study was to investigate whether fractures of fresh bones reveal a distinct microcracking pattern compared to fractures of dry bones, in order to optimise the fracture timing. To this purpose, we histologically analysed perimortem and postmortem fractures in human humeri. The fresh bones were retrieved from traumatic autopsy cases, and the dry bones from donors which were experimentally fractured. Our results showed that the highest density and length of microcracks (MCKs) were found in the interstitial area of dry fractured bones, which may be considered a marker of postmortem damage. In fresh fractured bones, we generally observed a lower density of MCKs, but a higher proportion of osteonal MCKs, which may be considered a marker of perimortem trauma. In summary, the results of our exploratory study suggest that changes in intrinsic bone factors (mineral/organic components) result in a different microcracking pattern that can be used in fracture timing.
Topics: Humans; Fractures, Bone; Autopsy; Forensic Pathology; Haversian System; Humerus; Postmortem Changes
PubMed: 36066767
DOI: 10.1007/s00414-022-02875-1 -
Journal of Bone and Mineral Research :... Oct 2022Hypophosphatasia (HPP) is the inherited error-of-metabolism caused by mutations in ALPL, reducing the function of tissue-nonspecific alkaline phosphatase...
Hypophosphatasia (HPP) is the inherited error-of-metabolism caused by mutations in ALPL, reducing the function of tissue-nonspecific alkaline phosphatase (TNAP/TNALP/TNSALP). HPP is characterized by defective skeletal and dental mineralization and is categorized into several clinical subtypes based on age of onset and severity of manifestations, though premature tooth loss from acellular cementum defects is common across most HPP subtypes. Genotype-phenotype associations and mechanisms underlying musculoskeletal, dental, and other defects remain poorly characterized. Murine models that have provided significant insights into HPP pathophysiology also carry limitations including monophyodont dentition, lack of osteonal remodeling of cortical bone, and differing patterns of skeletal growth. To address this, we generated the first gene-edited large-animal model of HPP in sheep via CRISPR/Cas9-mediated knock-in of a missense mutation (c.1077C>G; p.I359M) associated with skeletal and dental manifestations in humans. We hypothesized that this HPP sheep model would recapitulate the human dentoalveolar manifestations of HPP. Compared to wild-type (WT), compound heterozygous (cHet) sheep with one null allele and the other with the targeted mutant allele exhibited the most severe alveolar bone, acellular cementum, and dentin hypomineralization defects. Sheep homozygous for the mutant allele (Hom) showed alveolar bone and hypomineralization effects and trends in dentin and cementum, whereas sheep heterozygous (Het) for the mutation did not exhibit significant effects. Important insights gained include existence of early alveolar bone defects that may contribute to tooth loss in HPP, observation of severe mantle dentin hypomineralization in an HPP animal model, association of cementum hypoplasia with genotype, and correlation of dentoalveolar defects with alkaline phosphatase (ALP) levels. The sheep model of HPP faithfully recapitulated dentoalveolar defects reported in individuals with HPP, providing a new translational model for studies into etiopathology and novel therapies of this disorder, as well as proof-of-principle that genetically engineered large sheep models can replicate human dentoalveolar disorders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Humans; Alkaline Phosphatase; Disease Models, Animal; Hypophosphatasia; Mutation; Sheep; Tooth Loss
PubMed: 36053890
DOI: 10.1002/jbmr.4666 -
Royal Society Open Science Aug 2022Lamellae are sheets of mineralized collagen 1-20 µm thick, extending over hundreds of µm in bone tissue, occupying bone's structural hierarchy at a level above... (Review)
Review
Lamellae are sheets of mineralized collagen 1-20 µm thick, extending over hundreds of µm in bone tissue, occupying bone's structural hierarchy at a level above collagen fibres and osteocytes, and below osteons and trabeculae. Osteons are tubular arrangements of lamellae surrounding central neurovascular canals. Lamellae in osteons are usually described as concentric cylinders based on their annular appearance in transverse section. In this review, I provide a perspective on current understanding of the relationship between geometry of the bone formation front and the shape of lamellae produced at it, reaching the conclusion that the 'closing cone' bone formation front in secondary osteonal remodelling must necessarily result in cone-shaped lamellae in the mature secondary osteon. Secondary osteons replace primary osteons through a tunnelling process of bone turnover, meaning that conical lamellae may become more common in older and damaged bone which is at greatest risk of fracture. Visualization and measurement of three-dimensional lamellar shape over hundreds of microns is needed to provide data for accurate micromechanical simulations. Treating secondary osteonal lamellae as a 'stack of cones' rather than 'nested cylinders' may have important implications for our appreciation of bone's function as a load-bearing tissue and of its behaviour in fracture.
PubMed: 35958092
DOI: 10.1098/rsos.220712 -
Journal of the Mechanical Behavior of... Oct 2022Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical...
Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs' jawbones, which is crucial for implant studies and a direct comparison to human tissue. In the present work, we demonstrate a multimodal framework to assess the jawbone quantity and quality for a minipig animal model that could be further extended to humans. Three minipig genotypes, commonly used in dental research, were examined: Yucatan, Göttingen, and Sinclair. Three animals per genotype were tested. Cortical bone samples were extracted from the premolar region of the mandible, opposite to the teeth growth. Global morphological, compositional, and mechanical properties were assessed using micro-computed tomography (micro-CT) together with Raman spectroscopy and nanoindentation measurements, averaged over the sample area. Local mineral-mechanical relationships were investigated with the site-matched Raman spectroscopy and micropillar compression tests. For this, a novel femtosecond laser ablation protocol was developed, allowing high-throughput micropillar fabrication and testing without exposure to high vacuum. At the global averaged sample level, bone relative mineralization demonstrated a significant difference between the genotypes, which was not observed from the complementary micro-CT measurements. Moreover, bone hardness measured by nanoindentation showed a positive trend with the relative mineralization. For all genotypes, significant differences between the relative mineralization and elastic properties were more pronounced within the osteonal regions of cortical bone. Site-matched micropillar compression and Raman spectroscopy highlighted the differences between the genotypes' yield stress and mineral to matrix ratios. The methods used at the global level (averaged over sample area) could be potentially correlated to the medical tools used to assess jawbone toughness and morphology in clinics. On the other hand, the local analysis methods can be applied to quantify compressive bone mechanical properties and their relationship to bone mineralization.
Topics: Animals; Cortical Bone; Humans; Jaw; Mandible; Swine; Swine, Miniature; X-Ray Microtomography
PubMed: 35947925
DOI: 10.1016/j.jmbbm.2022.105405