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Frontiers in Immunology 2020Osteoporosis stems from an unbalance between bone mineral resorption and deposition. Among the numerous cellular players responsible for this unbalance bone marrow (BM)... (Review)
Review
Osteoporosis stems from an unbalance between bone mineral resorption and deposition. Among the numerous cellular players responsible for this unbalance bone marrow (BM) monocytes/macrophages, mast cells, T and B lymphocytes, and dendritic cells play a key role in regulating osteoclasts, osteoblasts, and their progenitor cells through interactions occurring in the context of the different bone compartments (cancellous and cortical). Therefore, the microtopography of immune cells inside trabecular and compact bone is expected to play a relevant role in setting initial sites of osteoporotic lesion. Indeed, in physiological conditions, each immune cell type preferentially occupies either endosteal, subendosteal, central, and/or perisinusoidal regions of the BM. However, in the presence of an activation, immune cells recirculate throughout these different microanatomical areas giving rise to a specific distribution. As a result, the trabeculae of the cancellous bone and endosteal free edge of the diaphyseal case emerge as the primary anatomical targets of their osteoporotic action. Immune cells may also transit from the BM to the depth of the compact bone, thanks to the efferent venous capillaries coursing in the Haversian and Volkmann canals. Consistently, the innermost parts of the osteons and the periosteum are later involved by their immunomodulatory action, becoming another site of mineral reabsorption in the course of an osteoporotic insult. The novelty of our updating is to highlight the microtopography of bone immune cells in the cancellous and cortical compartments in relation to the most consistent data on their action in bone remodeling, to offer a mechanist perspective useful to dissect their role in the osteoporotic process, including bone damage derived from the immunomodulatory effects of endocrine disrupting chemicals.
Topics: Animals; Bone Remodeling; Bone and Bones; Endocrine Disruptors; Humans; Immune System; Immunologic Factors; Osteoporosis
PubMed: 33013826
DOI: 10.3389/fimmu.2020.01737 -
Biofabrication Mar 2019Bone tissue engineers are facing a daunting challenge when attempting to fabricate bigger constructs intended for use in the treatment of large bone defects, which is...
Bone tissue engineers are facing a daunting challenge when attempting to fabricate bigger constructs intended for use in the treatment of large bone defects, which is the vascularization of the graft. Cell-based approaches and, in particular, the use of in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) has been one of the most explored options. We present in this paper an alternative method to mimic the spatial pattern of HUVECs and hMSCs found in native osteons based on the use of extrusion-based 3D bioprinting (3DP). We developed a 3DP biphasic osteon-like scaffold, containing two separate osteogenic and vasculogenic cell populations encapsulated in a fibrin bioink in order to improve neovascularization. To this end, we optimized the fibrin bioink to improve the resolution of printed strands and ensure a reproducible printing process; the influence of printing parameters on extruded strand diameter and cell survival was also investigated. The mechanical strength of the construct was improved by co-printing the fibrin bioink along a supporting PCL carrier scaffold. Compressive mechanical testing showed improved mechanical properties with an average compressive modulus of 131 ± 23 MPa, which falls in the range of cortical bone. HUVEC and hMSC laden fibrin hydrogels were printed in osteon-like patterns and cultured in vitro. A significant increase in gene expression of angiogenic markers was observed for the biomimetic scaffolds. Finally, biphasic scaffolds were implanted subcutaneously in rats. Histological analysis of explanted scaffolds showed a significant increase in the number of blood vessels per area in the 3D printed osteon-like scaffolds. The utilization of these scaffolds in constructing biomimetic osteons for bone regeneration demonstrated a promising capacity to improve neovascularization of the construct. These results indicates that proper cell orientation and scaffold design could play a critical role in neovascularization.
Topics: Animals; Bioprinting; Cattle; Cell Line; Fibrin; Haversian System; Human Umbilical Vein Endothelial Cells; Humans; Ink; Mesenchymal Stem Cells; Mice; Neovascularization, Physiologic; Rats, Sprague-Dawley; Swine; Tissue Scaffolds
PubMed: 30769337
DOI: 10.1088/1758-5090/ab078a -
Medicina (Kaunas, Lithuania) Jun 2022Background and Objectives: The gold standard for a successful prosthetic approach is the osseointegration of an implant. However, this integration can be a problem in...
Background and Objectives: The gold standard for a successful prosthetic approach is the osseointegration of an implant. However, this integration can be a problem in cases where the implant needs to be removed. Removing the implant with minimal damage to the surrounding tissues is important. Osteocytes cannot survive below −2 °C, but epithelial cells, fibroblasts, and other surrounding tissue cells can. Remodeling can be triggered by cryotherapy at temperatures that specifically affect osteocyte necrosis. In this study, we aimed to develop a method for reversing the osseointegration mechanism and for protecting the surrounding tissues by bone remodeling induced by CO2 cryotherapy. Materials and Methods: In this study, eight 2.8 mm diameter, one-piece mini implants were used in New Zealand rabbit tibias. Two control and six implants were tested in this study. After 2 months of osseointegration, a reverse torque force method was used to remove all osseointegrated implants at 5, 10, 20, and 30 Ncm. The osseointegration of the implants was proven by periotest measurements. Changes in bone tissue were examined in histological sections stained with toluidine blue after rabbit sacrifice. The number of lacunae with osteocyte, empty lacunae, and lacunae greater than 5 µm and the osteon number in a 10,000 µm2 area were calculated. Cryotherapy was applied to the test implants for 1 min, 2 min, and 5 min. Three implants were subjected to cryotherapy at −40 °C, and the other implants were subjected to cryotherapy at −80 °C. Results: Empty lacunae, filled osteocytes, lacunae >5 µm, and the osteon count around the implant applied at −40 °C were not significantly different from the control implants. The application of −40 °C for 1 min was found to cause minimal damage to the bone cells. The implants, which were applied for 1 min and 2 min, were successfully explanted on the 2nd day with the 5 Ncm reverse torque method. Test implants, which were applied cold for 5 min, were explanted on day 1. Tissue damage was detected in all test groups at −80 °C. Conclusions: The method of removing implants with cryotherapy was found to be successful in −40 °C freeze−thaw cycles applied three times for 1 min. To prove implant removal with cryotherapy, more implant trials should be conducted.
Topics: Animals; Dental Implants; Osseointegration; Rabbits; Tibia; Titanium; Torque
PubMed: 35888569
DOI: 10.3390/medicina58070849 -
Frontiers in Endocrinology 2020Bone possesses a highly complex hierarchical structure comprised of mineral (~45% by volume), organic matrix (~35%) and water (~20%). Water exists in bone in two forms:... (Review)
Review
Bone possesses a highly complex hierarchical structure comprised of mineral (~45% by volume), organic matrix (~35%) and water (~20%). Water exists in bone in two forms: as bound water (BW), which is bound to bone mineral and organic matrix, or as pore water (PW), which resides in Haversian canals as well as in lacunae and canaliculi. Magnetic resonance (MR) imaging has been increasingly used for assessment of cortical and trabecular bone. However, bone appears as a signal void on conventional MR sequences because of its short T2. Ultrashort echo time (UTE) sequences with echo times (TEs) 100-1,000 times shorter than those of conventional sequences allow direct imaging of BW and PW in bone. A series of quantitative UTE MRI techniques has been developed for bone evaluation. UTE and adiabatic inversion recovery prepared UTE (IR-UTE) sequences have been developed to quantify BW and PW. UTE magnetization transfer (UTE-MT) sequences have been developed to quantify collagen backbone protons, and UTE quantitative susceptibility mapping (UTE-QSM) sequences have been developed to assess bone mineral.
Topics: Animals; Bone Density; Cortical Bone; Echo-Planar Imaging; Humans; Magnetic Resonance Imaging; Time Factors; Water; X-Ray Microtomography
PubMed: 33071975
DOI: 10.3389/fendo.2020.567417 -
Acta Biomaterialia May 2023Bone fragility is a profound complication of type 1 diabetes mellitus (T1DM), increasing patient morbidity. Within the mineralized bone matrix, osteocytes build a...
Bone fragility is a profound complication of type 1 diabetes mellitus (T1DM), increasing patient morbidity. Within the mineralized bone matrix, osteocytes build a mechanosensitive network that orchestrates bone remodeling; thus, osteocyte viability is crucial for maintaining bone homeostasis. In human cortical bone specimens from individuals with T1DM, we found signs of accelerated osteocyte apoptosis and local mineralization of osteocyte lacunae (micropetrosis) compared with samples from age-matched controls. Such morphological changes were seen in the relatively young osteonal bone matrix on the periosteal side, and micropetrosis coincided with microdamage accumulation, implying that T1DM drives local skeletal aging and thereby impairs the biomechanical competence of the bone tissue. The consequent dysfunction of the osteocyte network hampers bone remodeling and decreases bone repair mechanisms, potentially contributing to the enhanced fracture risk seen in individuals with T1DM. STATEMENT OF SIGNIFICANCE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that causes hyperglycemia. Increased bone fragility is one of the complications associated with T1DM. Our latest study on T1DM-affected human cortical bone identified the viability of osteocytes, the primary bone cells, as a potentially critical factor in T1DM-bone disease. We linked T1DM with increased osteocyte apoptosis and local accumulation of mineralized lacunar spaces and microdamage. Such structural changes in bone tissue suggest that T1DM speeds up the adverse effects of aging, leading to the premature death of osteocytes and potentially contributing to diabetes-related bone fragility.
Topics: Humans; Osteocytes; Diabetes Mellitus, Type 1; Aging; Bone and Bones; Apoptosis
PubMed: 36878337
DOI: 10.1016/j.actbio.2023.02.037 -
Journal of Maxillofacial and Oral... Jun 2022Osteomyelitis is inflammation of medullary cavities, haversian system and adjacent cortex of bone. It is devastating to patients when invasive.
BACKGROUND
Osteomyelitis is inflammation of medullary cavities, haversian system and adjacent cortex of bone. It is devastating to patients when invasive.
AIM
The purpose of this study is to retrospectively review patients diagnosed with diabetic maxillary osteomyelitis and evaluate factors relating infection & diabetes.
METHODOLOGY
Case records of patients diagnosed with diabetic maxillary osteomyelitis were studied. Patient's demographic data, predisposing factors, etiology, clinical features, culture sensitivity reports, microbiology, treatment and complications were studied. Diabetic status was confirmed by glycosylated hemoglobin (HbA1c) test. Duration of diabetes and anti-diabetic medication adherence was also studied.
RESULTS
There were 28 patients diagnosed with diabetic maxillary osteomyelitis, (23-male; 5-female). Majority of the patients (60.7%) belonged to fourth & fifth decades. Twenty (71.4%) patients had poorly controlled diabetes (HbA1c > 8%). All patients reported with random blood sugar > 200 mg/dl. Thirteen patients (46.4%) were diagnosed for diabetes on admission and 11 patients (39.3%) had poor anti-diabetic medication adherence. Predominant etiology was odontogenic infection (50%). Cases of bacterial osteomyelitis (50%) were more frequent than those of fungal osteomyelitis (32.1%). Recurrence was observed in three cases.
CONCLUSION
Non-cognizance about diabetes mellitus can prove devastating for maxillofacial region and may prove fatal for the patient.
PubMed: 35712438
DOI: 10.1007/s12663-020-01371-6 -
Journal of Anatomy Jun 2019Bone can adapt to its habitual load history at various levels of its hierarchical structural and material organization. However, it is unclear how strongly a bone's...
Collagen fiber orientation pattern, osteon morphology and distribution, and presence of laminar histology do not distinguish torsion from bending in bat and pigeon wing bones.
Bone can adapt to its habitual load history at various levels of its hierarchical structural and material organization. However, it is unclear how strongly a bone's structural characteristics (e.g. cross-sectional shape) are linked to microstructural characteristics (e.g. distributions of osteons and their vascular canals) or ultrastructural characteristics [e.g. patterns of predominant collagen fiber orientation (CFO)]. We compared the cross-sectional geometry, microstructure and ultrastructure of pigeon (Columba livia domestica) humeri, and third metacarpals (B3M) and humeri of a large bat (Pteropus poliocephalus). The pigeon humerus is habitually torsionally loaded, and has unremodeled ('primary') bone with vessels (secondary osteons are absent) and high 'laminarity' because a large majority of these vessels course circularly with respect to the bone's external surface. In vivo data show that the bat humerus is also habitually torsionally loaded; this contrasts with habitual single-plane bending of the B3M, where in vivo data show that it oscillates back and forth in the same direction. In contrast to pigeon humeri where laminar bone is present, the primary tissue of these bat bones is largely avascular, but secondary osteons are present and are usually in the deeper cortex. Nevertheless, the load history of humeri of both species is prevalent/predominant torsion, producing diffusely distributed shear stresses throughout the cross-section. We tested the hypothesis that despite microstructural/osteonal differences in these pigeon and bat bones, they will have similar characteristics at the ultrastructural level that adapt each bone for its load history. We postulate that predominant CFO is this characteristic. However, even though data reported in prior studies of bones of non-flying mammals suggest that CFO would show regional variations in accordance with the habitual 'tension regions' and 'compression regions' in the direction of unidirectional habitual bending, we hypothesized that alternating directions of bending within the same plane would obviate these regional/site-specific adaptations in the B3M. Similarly, but for other reasons, we did not expect regional variations in CFO in the habitually torsionally loaded bat and pigeon humeri because uniformly oblique-to-transverse CFO is the adaptation expected for the diffusely distributed shear stresses produced by torsion/multidirectional loads. We analyzed transverse sections from mid-diaphyses of adult bones for CFO, secondary osteon characteristics (size, shape and population density), cortical thickness in quadrants of the cortex, and additional measures of cross-sectional geometry, including the degree of circular shape that can help distinguish habitual torsion from bending. Results showed the expected lack of regional CFO differences in quasi-circular shaped, and torsionally loaded, pigeon and bat humeri. As expected, the B3M also lacked CFO variations between the opposing cortices along the plane of bending, and the quasi-elliptical cross-sectional shape and regional microstructural/osteonal variations expected for bending were not found. These findings in the B3M show that uniformity in CFO does not always reflect habitual torsional loads. Osteon morphology and distribution, and presence of laminar histology also do not distinguish torsion from bending in these bat and pigeon wing bones.
Topics: Adaptation, Physiological; Animals; Biomechanical Phenomena; Chiroptera; Collagen; Columbidae; Haversian System; Stress, Mechanical; Wings, Animal
PubMed: 30924933
DOI: 10.1111/joa.12981 -
Surgical and Radiologic Anatomy : SRA Aug 2020The aim of this study is to describe the number and location of the nutrient foramina in human scapulae which can minimize blood loss during surgery.
PURPOSE
The aim of this study is to describe the number and location of the nutrient foramina in human scapulae which can minimize blood loss during surgery.
METHODS
30 cadaveric scapulae were macerated to denude the skeletal tissue. The nutrient foramina of 0.51 mm and larger were identified and labeled by adhering glass beads. CT scans of these scapulae were segmented resulting in a surface model of each scapula and the location of the labeled nutrient foramina. All scapulae were scaled to the same size projecting the nutrient foramina onto one representative scapular model.
RESULTS
Average number of nutrient foramina per scapula was 5.3 (0-10). The most common location was in the supraspinous fossa (29.7%). On the costal surface of the scapula, most nutrient foramina were found directly inferior to the suprascapular notch. On the posterior surface, the nutrient foramina were identified under the spine of the scapula in a somewhat similar fashion as those on the costal surface. Nutrient foramina were least present in the peri-glenoid area.
CONCLUSION
Ninety percent of scapulae have more than one nutrient foramen. They are located in specific areas, on both the posterior and costal surface.
Topics: Adult; Aged; Aged, 80 and over; Blood Loss, Surgical; Cadaver; Dissection; Female; Fiducial Markers; Haversian System; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Scapula; Tomography, X-Ray Computed
PubMed: 32112283
DOI: 10.1007/s00276-020-02441-7 -
Canadian Journal of Surgery. Journal... Aug 1998Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint... (Review)
Review
Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis.
Topics: Animals; Arthritis, Rheumatoid; Bone Diseases; Bone Remodeling; Bone Resorption; Bone and Bones; Cartilage, Articular; Diphosphonates; Humans; Osteoblasts; Osteoclasts
PubMed: 9711159
DOI: No ID Found -
BoneKEy Reports 2015Microdamage resulting from fatigue or 'wear and tear' loading contributes to bone fragility; however, the full extent of its influence is not completely understood.... (Review)
Review
Microdamage resulting from fatigue or 'wear and tear' loading contributes to bone fragility; however, the full extent of its influence is not completely understood. Linear microcracks (∼50-100 μm) and diffuse damage (clusters of sublamellar-sized cracks) are the two major bone microdamage types, each with different mechanical and biological consequences. Healthy bone, due to its numerous microstructural interfaces and its ability to affect matrix level repair, deals effectively with microdamage. From a material standpoint, healthy bone behaves much like engineering composites like carbon-fiber reinforced plastics. Both materials allow matrix damage to form during fatigue loading and use microstructural interfaces to dissipate energy and limit microcrack propagation to slow fracture. The terms fracture toughness and 'toughening mechanism', respectively, describe mechanical behavior and microstructural features that prevent crack growth and make it harder to fracture a material. Critically, toughness is independent of strength. In bone, primary toughening features include mineral and collagen interfaces, lamellae and tissue heterogeneity among osteons. The damage tolerance of bone and other composites can be overcome with sustained loading and/or matrix changes such that the microstructure no longer limits microcrack propagation. With reduced remodeling due to aging, disease or remodeling suppression, microdamage accumulation can occur along with loss of tissue heterogeneity. Both contribute additively to reduced fracture toughness. Thus, the answer to the key question for bone fragility of how much microdamage is too much is extremely complex. It ultimately depends on the interplay between matrix damage content, internal repair and effectiveness of matrix-toughening mechanisms.
PubMed: 25848533
DOI: 10.1038/bonekey.2015.11