Structure Of Osteons Research Articles

Legg – Calve – Perthes disease: Modification of the experimental design and its morphological criteria

Legg – Calve – Perthes disease (LCPD) is the most common femoral head osteonecrosis in children. Until now, the knowledge of etiology, pathogenesis and clinical signs is partial and does not provide a coherent view of the disease. Despite modern advances in understanding and diagnosing of the disease, surgical interventions and stress release remain the standard treatment methods. Now there is a need to develop both new strategies for studying the pathogenesis of the disease and choosing methods of its treatment.The aim. Reproduction and development of morphological criteria for the early stage of Legg – Calve – Perthes disease (stages 1–2 by the modified Waldenström classification system).Materials and methods. The research involved 6 young gray giant rabbits (Flandres) aged 3–4 months. The early stages of LCPD were simulated by the pathophysiological model of Kuzhelivsky I.I. et al. (2016) with paraarticular adrenaline injections along with physical activity. We modified the physical activity regime for the subjects by daily free range for 1.5–3 hours.Results. The experiment confirmed the validity of the modified simulation and designed its morphological criteria. The osteochondropathy process was verified histologically, we also revealed the classic signs of damage to subchondral bone and hyaline cartilage as well as abnormal vascularization of cartilage sites and pathological neoangiogenesis.Conclusion. The technique of non-traumatic osteonecrosis simulation in young rabbits featured initial results in reproducing the pathological links of osteonecrosis process. The cartilage tissue featured the loss of isogeneity in chondrocytes structure and their column-like arrangement; its delamination and replacement with fibrous tissue, including fibroblast-like cells and collagen fibers; cartilage neovascularization and persistent mixed hyperemia. In the bone marrow, only the activation of the red blood cell line was noted. The bone tissue featured the abnormality of osteon structure with a mosaic arrangement of trabeculae as well as lacunar resorption, and osteoblast degeneration.

Correlative Raman spectroscopy and electron microscopy identifies glycogen rich deposits correlated with local structural defects in long bones of type IV osteogenesis imperfecta patients

Osteogenesis imperfecta (OI) is a genetic bone disease occurring in approximately 1 in 10,000 births, usually as a result of genetic mutation. OI patients suffer from increased fracture risk and – depending on the severity of the disease – deformation of the limbs, which can even lead to perinatal death.Despite extensive studies, the way in which the genetic mutation is translated into structural and compositional anomalies of the tissue is still an open question. Different observations have been reported, ranging from no structural (or chemical) differences to completely chaotic bone structure and composition.Here, we investigated bone samples from two adolescent OI-IV patients, focusing on the bone structure and chemistry in naturally occurring fractures. The exposed fracture plane allows the investigation of the structure and composition of the weakest bone plane. We do so by combining scanning electron microscopy (SEM) imaging with chemical information from Raman microscopy.The exposed fracture planes show different regions within the same tissue, displaying normal osteonal structures next to disorganized osteons and totally disordered structures, while the collagen mineralization in all cases is similar to that of a healthy bone.In addition, we also detected significant amounts of depositions of glycogen-rich, organic, globules of 250–1000 nm in size. These depositions point to a role of cellular disfunction in the disorganization of the collagen in qualitative OI.Overall, our results unite multiple, sometimes contradicting views from the literature on qualitative OI.

The Gross Anatomical and Histological Features of the Humerus in African Green Monkeys (Chlorocebus sabaeus) from Saint Kitts and Nevis, West Indies

This paper presents a detailed gross description of all anatomical elements of the humerus in the African green monkey and provides comparative and differential elements on monkey osteology. The osteometric investigation adds value to the gross morphological investigation, adjoining metric data to the gross descriptive data set. An in-depth investigation of the microstructural aspects of the humeral bone tissue is provided, with qualitative and quantitative details and potential for diagnostic applications. Of the gross morphological elements described, several unique features specific to this species include the humeral head shape that presents with distinctive low convexity and caudal placement, the shape of the intertubercular groove, the less developed greater tubercle, and the disposition of the rotator cuff muscle insertion. Furthermore, the overall cranio-lateral curvature of the bone shaft was found to have a distinctive 154–155 degree of angulation of the diaphysis, and the well-developed medial epicondyle was observed with its distinctive medio-caudal retroflexion. The histological investigation was more indicative of a typical non-primate organization of the bone tissue, with laminar vascular and avascular structures combined with the presence of the secondary Haversian system involving a mixture of scattered and dense unorganized secondary osteonal structures. The histomorphometric investigation yielded metrical data for the secondary osteonal structures in terms of area (20,331 ± 5105 µm2), perimeter, and vascular canal area (64,769 ± 257 µm2).

A 3-Dimensional Scaffolding System Recapitulates the Hierarchical Osteon Structure.

The bone is composed of solid cortical bone and honeycomb-like trabecular bone. Although the cortical bone provides the substantial mechanical strength of the bone, few studies have focused on its regeneration. As the structural and functional units of the cortical bone, osteons play critical roles in bone turnover. Composed of osteocytes, lamellae, lacunocanalicular network, and Haversian canals, osteons exhibit a delicate and hierarchical architecture. Studies have attempted to reconstruct the osteonal structure with artificial approaches; however, hardly the four elements were recapitulated simultaneously. In this work, a series of bioengineering techniques, including electrospinning, micropatterning, and laser-directed microfabrication, were employed to develop a three-dimensional scaffolding system, which successfully recapitulated the osteon structure in vitro. The physiological morphology and bioactivity of osteocytes were emulated, the intercellular communications between osteocytes were identified, and the concentric lamellae and Haversian canals were simulated as well. This work constructed an in vivo-like platform for osteon study, providing convenience for exploring the interaction among the osteonal elements.

Increased AGE Cross-Linking Reduces the Mechanical Properties of Osteons

The osteon is the primary structural component of bone, contributing significantly to its unique toughness and strength. Despite extensive research on osteonal structure, the properties of osteons have not been fully investigated, particularly within the context of bone fragility diseases like type 2 diabetes mellitus (T2DM). This study aims to isolate osteons from bovine bone, simulate the effects of increased advanced glycation end-products (AGEs) in T2DM through ribosylation, and evaluate the mechanical properties of isolated osteons. Osteons extracted from the posterior section of bovine femur mid-diaphysis were processed to achieve a sub-millimeter scale for microscale imaging. Subsequently, synchrotron radiation micro-computed tomography was employed to precisely localize and isolate the osteon internally. While comparable elastic properties were observed between control and ribosylated osteons, the presence of AGEs led to decreased strain to failure. Young’s modulus was quantified (9.9 ± 4.9 GPa and 8.7 ± 3 GPa, respectively), aligning closely with existing literature. This study presents a novel method for the extraction and isolation of osteons from bone and shows the detrimental effect of AGEs at the osteonal level.

Polyhydroxybutyrate-based osteoinductive mineralized electrospun structures that mimic components and tissue interfaces of the osteon for bone tissue engineering.

Scaffolds for bone tissue engineering should enable regeneration of bone tissues with its native hierarchically organized ECM and multiple tissue interfaces. To achieve this, inspired by the structure and properties of bone osteon, we fabricated polyhydroxybutyrate-based mineralized electrospun fibrous scaffolds. After studying multiple polyhydroxybutyrate (PHB)-based fibers, we chose 7%PHB/1%Gelatin fibers (PG) to fabricate mineralized fibers that mimic mineralized collagen fibers in bone. The mineralized PG (mPG) surface had a rough, hydrophilic layer of low crystalline calcium phosphate which was biocompatible to BMSCs, induced their proliferation and was osteoinductive. Subsequently, by modulating the electrospinning process, we fabricated mPG-based novel higher order fibrous scaffolds that mimic the macroscale geometries of osteons of bone ECM. Inspired by the aligned collagen fibers in bone lamellae, we fabricated mPG scaffolds with aligned fibers that could direct anisotropic elongation of mBMSCs. Further, we fabricated electrospun mPG-based osteoinductive tubular constructs which can mimic cylindrical bone components like osteons or lamellae or be used as long bone analogues based on their dimensions. Finally, to regenerate tissue interfaces in bone, we introduced a novel bi-layered scaffold-based approach. An electrospun bi-layered tubular construct that had PG in the outer layer and 7%PHB/0.5%Polypyrrole fibers (PPy) in the inner layer was fabricated. The bi-layered tubular construct underwent preferential surface mineralization only on its outer layer. This outer mineralized layer supported osteogenesis while the inner PPy layer could support neural cell growth. Thus, the bi-layered tubular construct may be used to regenerate haversian canal in the osteons which hosts nerve fibers. Overall, the study introduced novel techniques to fabricate biomimetic structures that can regenerate components of bone osteon and its multiple tissue interfaces. The study lays foundation for the fabrication of a modular scaffold that can regenerate bone with its hierarchical structure and complex tissue interfaces.

Biomimetic Nacre-like Hydroxyapatite/Polymer Composites for Bone Implants.

One of the most ambitious goals for bone implants is to improve bioactivity, incapability, and mechanical properties; to reduce the need for further surgery; and increase efficiency. Hydroxyapatite (HA), the main inorganic component of bones and teeth, has high biocompatibility but is weak and brittle material. Cortical bone is composed of 70% calcium phosphate (CaP) and 30% collagen and forms a complex hierarchical structure with anisotropic and lamellar microstructure (osteons) which makes bone a light, strong, tough, and durable material that can support large loads. However, imitation of concentric lamellar structure of osteons is difficult to achieve in fabrication. Nacre from mollusk shells with layered structures has now become the archetype of the natural "model" for bio-inspired materials. Incorporating a nacre-like layered structure into bone implants can enhance their mechanical strength, toughness, and durability, reducing the risk of implant catastrophic failure or fracture. The layered structure of nacre-like HA/polymer composites possess high strength, toughness, and tunable stiffness which matches that of bone. The nacre-like HA/polymer composites should also possess excellent biocompatibility and bioactivity which facilitate the bonding of the implant with the surrounding bone, leading to improved implant stability and long-term success. To achieve this, a bi-directional freeze-casting technique was used to produce elongated lamellar HA were further densified and infiltrated with polymer to produce nacre-like HA/polymer composites with high strength and fracture toughness. Mechanical characterization shows that increasing the ceramic fractions in the composite increases the density of the mineral bridges, resulting in higher flexural and compressive strength. The nacre-like HA/(methyl methacrylate (MMA) + 5 wt.% acrylic acid (AA)) composites with a ceramic fraction of 80 vol.% showed a flexural strength of 158 ± 7.02 MPa and a Young's modulus of 24 ± 4.34 GPa, compared with 130 ± 5.82 MPa and 19.75 ± 2.38 GPa, in the composite of HA/PMMA, due to the higher strength of the polymer and the interface of the composite. The fracture toughness in the composition of 5 wt.% PAA to PMMA improves from 3.023 ± 0.98 MPa·m1/2 to 5.27 ± 1.033 MPa·m1/2 by increasing the ceramic fraction from 70 vol.% to 80 vol.%, respectively.

Automatic Segmentation of Osteonal Microstructure in Human Cortical Bone Using Deep Learning: A Proof of Concept.

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.

Research on biomimetic design and impact characteristics of periodic multilayer helical structures.

Osteons are composed of concentric lamellar structure, the concentric lamellae are composed of periodic thin and thick sub-lamellae, and every 5 sub-lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four biomimetic models with different fiber helix angles were established and fabricated according to the micro-nano structure of osteon. The effects of the fiber periodic helical structure on impact characteristic and energy dissipation of multi-layer biomimetic composite were investigated. The calculation results indicated that the stress distribution, contact characteristics and fiber failur during impact, and energy dissipation of the composite are affected by the fiber helix angle. The stress concentration of composite materials under external impact can be effectively improved by adjusting the fiber helix angle when the material composition and material performance parameters are same. Compared with the sample30, the maximum stress of sample60 and sample90 increases by 38.1% and 69.8%, respectively. And the fiber failure analysis results shown that the model with a fiber helix angle of 30° has a better resist impact damage. The drop-weight test results shown that the impact damage area of the specimen with 30° helix angle is smallest among the four types of biomimetic specimens. The periodic helical structure of mineralized collagen fibers in osteon can effectively improve the impact resistance of cortical bone. The research results can provide useful guidance for the design and manufacture of high-performance, impact-resistant biomimetic composite materials.

Biologic Bone Behavior During the Osseointegration Process: Histologic, Histomorphometric, and SEM-EDX Evaluations.

This study evaluated bone behavior during dynamic osseointegration. A total of 12 implants were placed in sheep tibia and analyzed at 15, 30, 60, and 90 days. Quantitative and qualitative bone behaviors were evaluated with histologic, histomorphometric, Alizarin Red S, and SEM-EDX (scanning electron microscopy with energy-dispersive x-ray spectroscopy) analysis. Twenty microanalyses were performed in chambers 1, 3, and 5 (a chamber is the distinctive space/bone volume between two coils of the implant screw) in distinctive zones: the titanium-bone interface (zone A), the middle chamber-bone front (zone B), the bone-surgical threading interface (zone C), and native bone (zone D; used as a control). The dynamic osseointegration index (DOI) and bone quality index (BQI) with calcium/phosphorus (Ca/P) content were detected to evaluate the osseointegration quality, bone-to-implant contact (BIC), and bone density around implants. At 15 days, initial bone formation with osteoid matrix deposition and different color intensities were observed (means: BIC = 23.3% ± 3.9%; DOI = 1.55). SEM-EDX analysis showed low mineralized bone/bone marrow with a very low Ca/P mean value. At 30 days, high new bone deposition with higher color intensity in the crestal portion was recorded (BIC = 77.3% ± 0.4%; DOI = 2.58). At 90 days, tight BIC to the middle and apical implant portions were detected, as well as several osteon structures in the crestal portion (BIC = 86.4% ± 0.6%; DOI = 0.96). During all observed time periods, the BQI showed 25% more Ca/P in zone A. Greater maturation degree and lower BQI were seen at zone A compared to the other zones. After 15 and 30 days, zones B and C (except for P in zone B) showed BQIs slightly over 50% and around 75%, respectively, confirming a progressively higher degree of bone maturation that proceeds with the osseointegration process. After 90 days, the BQI values of zones B and C (greater than 70% in zone B and around 90% in zone C) confirmed the bone mineralization and maturation process and an acceleration of implant osseointegration, while a lower BQI value (25%) was recorded in zone A. This study shows osseointegration as a variable dynamic process with a higher bone deposition in contact with the implant surface during the early phase, while in the active and later osseointegration times, the bone quality maturation showed higher values only "at distance" (growth of native bone to the implant surface, observed later in the osseointegration process). After 3 months (before loading), the BQI evaluation was lower (25%) in zone A, confirming that the healing and maturation process of the bone cannot be considered complete.

Bionic design based on micro-nano structure of osteon and its low-velocity impact damage behavior

It is found that the osteon is composed of thin and thick lamellae which are periodic and approximately concentric, every 5 lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four bionic composite models with different fiber helix angles were established and fabricated according to the microstructure of mineralized collagen fibers in osteon. Based on the impact analysis of four kinds of bionic composite models, the effects of the fiber periodic spiral structure on the impact resistance and energy dissipation of multi-layer bionic composite were investigated. The analysis results show that the fiber helix angle affects the impact damage resistance and energy dissipation of multi-layer fiber reinforced composites. Among the 4 kinds of multi-layer composite models, the composite model with helix angle of 30° has better comprehensive ability to resist impact damage. The test results show that the impact damage area of the specimen with 30° helix angle is smallest among the 4 types of bionic specimens, which is consistent with the results of finite-element impact analysis. Furthermore, in the case of without impact damage, the smaller the fiber helix angle is, the more uniform the stress distribution is and more energy is dissipated in the impact process. The periodic spiral structure of mineralized collagen fibers in osteon are the result of natural selection of biological evolution. This structure can effectively improve the ability of cortical bone to resist external impact. The research results can provide useful guidance for the design and manufacture of high-performance and strong impact resistant bionic composites.Graphical

Phase field models of interface failure for bone application - evaluation of open-source implementations

Bone is a composite material where tubular osteon structures surrounded by thin interfaces reinforce the tissue at the microscale. These interfaces provide alternative weak paths for crack growth and give rise to potent extrinsic toughening mechanisms. Numerical models can help to gain a deeper understanding of fracture resistance in bone, however, capturing the interface mechanics is key. For this purpose, the phase field method for fracture is appealing due to its capability of capturing complex cracking phenomena. Still, it is far from well-established in the field of biomechanics. In this study, we evaluated a selection of recent open-source implementations of the phase field method to find the best approach for simulating crack growth in bone tissue. We also proposed a new method for correcting the interface fracture toughness in a phase field model. The selected implementations were compared using benchmark tests, including single edge notched tensile specimens with and without interfaces, as well as models representing typical bone geometries. We found the quasi-Newton monolithic solvers to be superior both in terms of computational speed and robustness compared to the evaluated staggered solvers. We also showed that correcting the fracture toughness of the interface is key for simulating crack patterns that are consistent with analytical predictions from linear elastic fracture mechanics.

MULTI-SCALE MECHANICAL BEHAVIOR ANALYSIS ON FLUID–SOLID COUPLING FOR OSTEONS IN VARIOUS GRAVITATIONAL FIELDS

Background: Compact bone mainly consists of cylindrical osteon structures. In microgravity, the change in the mechanical microenvironment of osteocytes might be the root cause of astronauts’ bone loss during space flights. Methods: A multi-scale three-dimensional (3D) fluid–solid coupling finite element model of osteons with a two-stage pore structure was developed using COMSOL software based on the natural structure of osteocytes. Gradients in gravitational fields of [Formula: see text]1, 0, 1, 2.5, and 3.7[Formula: see text]g were used to investigate the changes in the mechanical microenvironment on osteocyte structure. The difference in arteriole pulsating pressure and static compression stress caused by each gravity gradient was investigated. Results: The mechanical response of osteocytes increased with the value of g, compared with the Earth’s gravitational field. For instance, the fluid pressure of osteocytes and the von Mises stress of bone matrix near lacunae decreased by 31.3% and 99.9%, respectively, in microgravity. Under static loading, only about 16.7% of osteocytes in microgravity and 58.3% of osteocytes in the Earth’s gravitational field could reach the fluid shear stress threshold of biological reactions in cell culture experiments. Compared with the Earth’s gravitational field, the pressure gradient inside osteocytes severely decreased in microgravity. Conclusion: The mechanical microenvironment of osteocytes in microgravity might cause significant changes in the mechanical microenvironment of osteocytes, which may lead to disuse osteoporosis in astronauts.

Evaluation of Streptococcus oralis adhesion and biofilm formation on laser-processed titanium

Abstract To prevent implant-associated infections, surface modifications need to be developed that prevent bacterial colonisation and biofilm formation. In the present study, titanium surfaces were processed by nanosecond-pulsed laser ablation to generate a variety of different structures (anatase, rutile, Osteon, as well as Osteon additionally coated with silver and clove nanoparticles). Analysis of adhesion and biofilm formation of the oral pioneer bacterium Streptococcus oralis could demonstrate antibacterial properties of anatase surfaces. For clinical translation, the effect should be enhanced by further adaption and combined with the osseointegrative Osteon structure

New Bone Formation in the Whole Decellularized Cortical Bone Scaffold Using the Model of Revitalizing a Haversian System.

Decellularized allogeneic bone chips act as scaffolds for bone tissue regeneration. Owing to their lack of osteogenic potentials compared to autologous bone graft, decellularized bone scaffolds (DBSs) have applied only to small partial bone defects in clinical settings. Furthermore, only decellularized cancellous bone chips have been limitedly used for the purpose of bone regeneration. The cortical bone has less porosity and less osteogenic materials such as bone morphogenetic proteins in comparison with cancellous bone. In this study, we tried to accelerate new bone formation within the decellularized cortical bone scaffold using a vascular pedicle as an in vivo bioreactor.Forty DBSs were divided into 4 groups with different conditionings (DBS+ demineralized bone matrix [DBM], DBS+DBM+me+mesenchymal stem cells, DBS+DBM+vascular pedicle, and DBS+DBM+vascular pedicle+mesenchymal stem cells) and implanted into the back of 5 rabbits. Half of the DBSs were examined at 8 weeks and the other half at 16 weeks to determine vascularization level and osteogenesis within each group. New bone formation and bone-forming cells related to osteogenesis were observed via histological staining. Inclusion of the vascular pedicle resulted in larger areas of bone regeneration. With time, osteon structures became more prominent in groups containing the vascular pedicle.In summary, vascularized DBSs combined with a vascular pedicle have shown promising results for bone regeneration, thereby representing potential therapeutic alternatives for autologous bone grafts or bone tissue free transfer in large or segmental bone defects. In addition, demineralized whole cortical bone matrix along with vascular pedicle and various bone inductive materials, such as DBM and recombinant human bone morphogenetic protein-2, may be an additional new option of an ideal osteoinductive system.

From rose petal to bone scaffolds: Using nature to fabricate osteon-like scaffolds for bone tissue engineering applications

In this study, rose petal was used to fabricate osteon-like scaffolds for bone tissue engineering applications. Rose petal was coupled with nanocrystalline forsterite colloid to mimic the lamellar structure of porous osteons. The microstructures on the surface of the petals were utilized as template for pores and lacuna spaces which are suitable for cell attachment. On the other hand, rolling the petals allowed us to form the osteon structure with haversian canal and lacuna spaces on the body of the samples. After trying different temperatures, the results showed that samples annealed at 1100 °C closely mimicked the lacuna spaces, haversian canal, and lamellar structures of osteons. These scaffolds had the pore diameter in the range of about 13–20 μm and presented good bioactivity and biocompatibility. It was found that red rose petal is a good candidate to be used as a template for designing scaffolds for bone tissue engineering applications.

Osteon: Structure, Turnover, and Regeneration.

Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone, there are few studies focusing on cortical bone repair or regeneration. Osteons (the Haversian system) form structural and functional units of cortical bone. In recent years, emerging evidences have shown that the osteon structure (including osteocytes, lamellae, lacunocanalicular network, and Haversian canals) plays critical roles in bone mechanics and turnover. Therefore, reconstruction of the osteon structure is crucial for cortical bone regeneration. This article provides a systematic summary of recent advances in osteons, including the structure, function, turnover, and regenerative strategies. First, the hierarchical structure of osteons is illustrated and the critical functions of osteons in bone dynamics are introduced. Next, the modeling and remodeling processes of osteons at a cellular level and the turnover of osteons in response to mechanical loading and aging are emphasized. Furthermore, several bioengineering approaches that were recently developed to recapitulate the osteon structure are highlighted. Impact statement This review provides a comprehensive summary of recent advances in osteons, especially the roles in bone formation, remodeling, and regeneration. Besides introducing the hierarchical structure and critical functions of osteons, we elucidate the modeling and remodeling of osteons at a cellular level. Specifically, we highlight the bioengineering approaches that were recently developed to mimic the hierarchical structure of osteons. We expect that this review will provide informative insights and attract increasing attentions in orthopedic community, shedding light on cortical bone regeneration in the future.

FGF7-induced E11 facilitates cell-cell communication through connexin43.

Fibroblast growth factors (FGFs) include a large family of growth factors that play a critical role in maintaining bone homeostasis, but the specific role of its members such as FGF7 does not well understand. Osteoblasts are a kind of major cells essential for bone formation. Osteoblasts interact with one another to create the unique structure of osteons. The well-connected osteons constitute the cortical bone. As an early osteocyte marker that triggers actin cytoskeleton dynamics, E11 is essential for osteoblasts' dendrites formation. However, the upstream which regulates E11 is mainly unknown. The purpose of this study was to examine the influence of FGF7 on the expression and the distribution of E11 in osteoblasts, which mediated osteoblasts' processes formation and gap junctional intercellular communication (GJIC) partly through connexin43 (Cx43). We first demonstrated that FGF7 increased the expression of E11 in osteoblasts. We then showed that FGF7 promoted osteoblasts' dendrites elongation and functional gap junctions formation. Furthermore, E11 interacted directly with Cx43 in primary osteoblasts. MAPK pathway and PI3K-AKT pathway were involved in the effect of FGF7. Our results shed light on the unique role of FGF7 on osteoblasts, which may indicate that FGF7 plays a more significant role in the later stages of bone development and homeostasis.

Manipulating Air-Gap Electrospinning to Create Aligned Polymer Nanofiber-Wrapped Glass Microfibers for Cortical Bone Tissue Engineering.

Osteons are the repeating unit throughout cortical bone, consisting of canals filled with blood and nerve vessels surrounded by concentric lamella of hydroxyapatite-containing collagen fibers, providing mechanical strength. Creating a biodegradable scaffold that mimics the osteon structure is crucial for optimizing cellular infiltration and ultimately the replacement of the scaffold with native cortical bone. In this study, a modified air-gap electrospinning setup was exploited to continuously wrap highly aligned polycaprolactone polymer nanofibers around individual 1393 bioactive glass microfibers, resulting in a synthetic structure similar to osteons. By varying the parameters of the device, scaffolds with polymer fibers wrapped at angles between 5–20° to the glass fiber were chosen. The scaffold indicated increased cell migration by demonstrating unidirectional cell orientation along the fibers, similar to recent work regarding aligned nerve and muscle regeneration. The wrapping decreased the porosity from 90% to 80%, which was sufficient for glass conversion through ion exchange validated by inductively coupled plasma. Scaffold degradation was not cytotoxic. Encapsulating the glass with polymer nanofibers caused viscoelastic deformation during three-point bending, preventing typical brittle glass fracture, while maintaining cell migration. This scaffold design structurally mimics the osteon, with the intent to replace its material compositions for better regeneration.

BIOCHEMICAL, HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL EVALUATION OF ALTERATIONS IN BLOOD AND TIBIAL BONE TISSUES OF OVARIECTOMIZED RATS IN THE ACUTE PHASE

AMAÇ: Menopoz sonrası meydana gelen osteoporoz, kemik kütlesinde azalma ve kemik dokunun yapısında bozulma ile sonuçlanır. Ovariektomi sonrası, osteoporoz bulgularına rastlanmakta ve kemik yıkımı kemik oluşumundan fazla olduğundan kemik kaybına neden olmaktadır. ADAMs transmembran proteinleri ekstrasellüler matriksin yeniden yapılandırılmasında ve embriyonik gelişim, hücre göçü, adezyon, anjiyogenez olmak üzere birçok fizyolojik süreçte rol alırlar. Çalışmamızın amacı, ovariektomi oluşturulan sıçanlarda kan ve kemik dokusunda akut dönemde meydana gelen değişikleri biyokimyasal, histopatolojik ve immünohistokimyasal yöntemlerle araştırmaktır.GEREÇ VE YÖNTEM: Sağlıklı ve dişi 20 adet erişkin Wistar albino sıçan kontrol (n:10) ve bilateral ovariektomi uygulanan grup (n:10) olmak üzere 2 gruba ayrıldı. Anestezi altında yumurtalık rahim boynu kısmından 2 cm'lik kesi yapılarak, iki dorsolateral insizyon ile uterus apeksinden çift taraflı yumurtalıklar ipek iplikle çıkarıldı. Ovariektomi den 1 hafta sonra, deney hayvanları feda edildi. Serum östrojen, kalsiyum ve alkalin fosfat değerlerini ölçmek için her hayvandan kan örnekleri alındı, tibia kemikleri çıkarılarak formalin çözeltisine alınarak tespit edildikten sonra, dekalsifiye etme işlemine tabi tutuldu ve rutin histolojik işlemlerin ardından parafin blokları hazırlandı, yarı-ince kesitleri alınarak histopatolojik incelemeler için Hematoksilen Eozin boyası ile boyandı. İmmünohistokimyasal analiz için, antijen retrival işlemini uygulamak üzere sitrat tamponuna alındıktan sonra hidrojen peroksit ile muamele edildi. Kesitlere anti-ADAMTS-1 primer antikoru uygulandı, ışık mikroskobunda değerlendirildi.BULGULAR: Kontrol grubunda radiyal tarzda dağılmış havers kanalları ve volkman kanalları izlenirken, kollajen lifler birbirine paralel ve düzenliydi. Ovariektomi grubunda ise kemik matriksinde dejeneratif değişiklikler, lamelli kemik yapısında bozulma izlendi. ADAMTS-1 ekspresyonu açısından, kontrol grubu osteoblast ve osteosit hücrelerinde ve kemik matriksindeki ince kollajen liflerde ekspresyon pozitifti. Ovariektomi grubunda, dejeneratif alanda yer alan osteoklast hücrelerinde ADAMTS-1 ekspresyonunda artış, osteon yapılarında, endotel hücrelerinde ADAMTS-1 pozitif ekspresyonu izlendi. Kanda östrojen değerleri açısından, ovariektomi grubunda kontrol grubuna göre anlamlı bir düşüş gözlendi. Kalsiyum değerlerinde ise kontrol ve ovariektomi gruplarının değerleri birbirine yakındı. Alkalen fosfataz değerlerinin ovariektomi grubunda yükseldiği görüldü(p=0,01).SONUÇ: Çalışmamız sonucu elde ettiğimiz veriler ışığında, osteoporoz tedavisine ADAMTS-1 proteinlerinin dahil edilmesinin yeni tedavi yöntemlerini destekleyebileceği düşüncesindeyiz.