Mature Bone Research Articles

Osteoid containing breast masses: A rad-path correlation

Objectives: Breast cancer is very common, of which the most common subtype is invasive ductal cancer (IDC). However, there are some rare types that also occur and manifest radiologically in a different manner. Our article aims to emphasize a rare type of breast neoplasm, which shows osteoid matrix on pathology, and to correlate their imaging findings, thus enabling differentiation from usual carcinoma and aiding in further pathology typing. Material and Methods: A retrospective audit of breast masses with osteoid matrix was done from 2008 to 2021. The cases were retrieved from pathology archives. Twenty-five such cases were found with histopathology reports mentioning the osteoid matrix. Eight patients from these 25 had pre-operative mammograms as well as histopathology available for review. We evaluated these with mammograms with multiple parameters. The project was approved by the Institutional Ethics Committee. Waiver of consent was obtained since there was no direct contact between the researcher and the participants. Results: Most cases of eccentric coarse calcification seen on mammography showed type IV matrix, in turn meaning that these cases had mature bone formation with tumor cell rimming type on histopathology. Three tumors produced an osteoid matrix in our study, namely, Metaplastic carcinoma, primary osteosarcoma, and malignant phyllodes tumor. Coarse calcification mostly indicates metaplastic carcinoma with osteosarcoma element. The preoperative diagnosis can guide pathology sampling. Conclusion: When eccentric, large, and coarse calcifications are visible within a mass on a mammogram, it raises suspicion of mature bone formation with tumor cell rimming within the tumor matrix.

Effect of electroacupuncture at "Jiaji" (EX-B2) on senescence of nucleus pulposus cells of degenerated lumbar intervertebral disc in rabbits.

To observe the effect of electroacupuncture (EA) at "Jiaji"(EX-B2) on body mass, motor function, expression of caveolin-1 (Cav-1) in nucleus pulposus cells and annulus fibrosus tissue, telomerase activi-ty, relative telomere length and different cell cycle ratio of nucleus pulposus cells in rabbits with intervertebral disc degeneration(IVDD), so as to investigate its mechanism underlying delaying senescence of the degenerated lumbar intervertebral disc nucleus pulposus cells. Twenty-five male New Zealand rabbits with mature bones were divided into control, sham operation, model, EA, and acupuncture groups, with 5 rabbits in each group. The IVDD model was established by inserting kirschner wires to the vertebral bone surface between the lumbar (L)4 and L5 vertebrae, followed by applying continuous axial pressure for 28 d. EA (2 Hz/15 Hz, 1-2 mA) or acupuncture (only insertion of acupuncture needles into bilateral EX-B2, but without electrical stimulation) was applied to bilateral EX-B2 for 20 min, once daily, 6 times a week for 4 weeks. The hindlimb locomotor function (locomotor score) was assessed by using Faden's and colleagues' methods. The general conditions of rabbits in each group were observed, and their body weight changes were measured every week. Nucleus pulposus cells were isolated using enzyme digestion method. After the treatment, the Cav-1 positive cell counts in nucleus pulposus cells and annulus fibrosus tissues were detected by immunohistochemistry, and the telomerase activity of nucleus pulposus cells was detected by PCR-ELISA. The relative telomere length of nucleus pulposus cells was measured by real-time quantitative polymerase chain reaction (real-time qPCR), and the cell cycle of nucleus pulposus was detected by flow cytometry. Compared with the sham operation group, the body mass from 4 to 11 week, locomotor score at 4, 7 and 11 week, telomerase activity, relative telomere length and the proportion of cells in G2/M phase of nucleus pulposus cells were significantly decreased (P<0.01), while Cav-1 positive cell counts of nucleus pulposus and annulus fibrosus tissue, and the proportion of nucleus pulposus cells in the G0/G1 phase considerably increased (P<0.01) in the model group. Relevant to the model group, the EA group rather than the acupuncture group had an increase in the body mass from 8 to 11 week, locomotor score at 11 week, telomerase activity, relative telomere length of nucleus pulposus cells, and the proportion of nucleus pulposus cells in G2/M phase (P<0.01), and a decrease in the Cav-1 positive cell counts of nucleus pulposus and annulus fibrosus tissue and the proportion of cells in G0/G1 phase (P<0.01). No significant differences were found between the model and acupuncture groups in all the indexes mentioned above. EA at EX-B2 has a bene-ficial effect in improving motor function in rabbits with IVDD, which may be related to its functions in reducing the expression of Cav-1 in nucleus pulposus cells and annulus fibrosus, improving cycle arrest, enhancing the telomerase activity and the relative telomere length of nucleus pulposus cells, delaying the senescence of nucleus pulposus cells of the degenerated lumbar intervertebral discs.

Tracheobronchopathia osteochondroplastica: a case report highlighting the importance of clinico-radiologic correlation

Tracheobronchopathia osteochondroplastica (TBPO) is a rare and benign idiopathic disease of the tracheobronchial tree, characterized by osseous, and/or cartilaginous submucosal nodules involving the anterior and lateral walls of the airways with sparing of the posterior wall. We present a case of a 51-year-old non-smoker female, presenting with a 2-year history of gradually enlarging anterior neck mass with foreign body sensation, frequent throat clearing, and occasional hoarseness. She was initially diagnosed with recurrent respiratory papillomatosis due to the presence of nodules on flexible laryngoscopy. A plain neck and chest CT then showed irregularity of the tracheal walls with calcified nodules projecting into the lumen, sparing the posterior wall, consistent with TBPO. Fiberoptic bronchoscopy with biopsy was also done which confirmed the inferior extent of the nodules down to the level of the carina, and the presence of fragments of mature bone tissue within the nodules.

Effect of in vivo implantation sites on the graft-to-bone osteointegration induced by gradient nanofibrous scaffolds

Gradient nanofibrous scaffolds hold great promise as viable ligament grafts to enhance graft-to-bone integration for long-term reconstruction of damaged anterior cruciate ligaments. However, the effect of in vivo implantation sites on graft-to-bone osteointegration induced by gradient scaffolds remains largely unexplored. Here, we systematically investigated the effects of nanofibrous scaffolds with fiber organization and nanoHA/BMP-2 gradients on graft-to-bone osteointegration by implanting them into tibial and femoral bone tunnels, respectively. The nanofibrous scaffolds were fabricated to possess gradient regions and uniform regions at two ends, and the gradient regions were implanted into femoral tunnels and tibial tunnels as two experimental groups. The biomechanical test showed that the ligament grafts broke in the intraarticular zone at 12 and 24 weeks of implantation, confirming a good biofixation between the grafts and bone tissues at both implantation sites of the tibial and femoral tunnels. Additionally, the gradient region of the ligament graft was found to enhance osteointegration and promote the formation of more secure graft-to-bone interfaces, as compared to uniform regions. In femoral bone tunnels, a relatively slow osteointegration process was observed even in the gradient region of the ligament grafts, which showed the formation of distinct fibrocartilage interfaces at 12 weeks and further evolved into mature bone tissues at 24 weeks. In tibial bone tunnels, higher nanoHA/BMP-2 content led to rapid penetration of newly-regenerated bone tissues in the gradient regions of the grafts at 12 weeks, followed by bone remodeling and complete integration with native tibial plateau at 24 weeks. These findings might provide new insights to develop biomimetic gradient scaffolds for matching the osteointegration process and speed in tibial and femoral bone tunnels.

Effect of in vitro ribosylation on the dynamic fracture behavior of mature bovine cortical bone

In this study, the fracture behavior of ribosylated bovine cortical bone is investigated under loading conditions simulating a fall event. Single edge notched specimens, separated into a control group (n = 11) and a ribosylated group (n = 8), were extracted from the mid-diaphysis of a single bovine femur harvested from a mature cow. A seven-day ribosylation process results in the accumulation of Advanced-Glycation End Products (AGEs) cross-links and AGE adducts. Specimens were subjected to symmetric three point bending (opening mode) and an impact velocity of 1.6 m/s using a drop tower. Near-crack displacement fields up to fracture initiation are determined from high-speed images post-processed using digital image correlation. A constrained over-deterministic least squares regression and orthotropic material linear elastic fracture mechanics theory are used to extract the in-plane critical stress intensity factors at fracture initiation (i.e., fracture initiation toughness values). Statistically significant differences were not observed when comparing the in-plane fracture initiation toughness values (p≥0.96) or energy release rate (p=0.90) between the control and seven-day ribosylated groups. The intrinsic variability of bone may require high sample numbers in order to achieve an adequately powered experiment when assessing dynamic fracture behavior. While there are no detectable differences due to the ribosylation treatment investigated, this is likely due to the limited sample sizes utilized.

Deep coverage and quantification of the bone proteome provides enhanced opportunities for new discoveries in skeletal biology and disease.

Dysregulation of cell signaling in chondrocytes and in bone cells, such as osteocytes, osteoblasts, osteoclasts, and an elevated burden of senescent cells in cartilage and bone, are implicated in osteoarthritis (OA). Mass spectrometric analyses provides a crucial molecular tool-kit to understand complex signaling relationships in age-related diseases, such as OA. Here we introduce a novel mass spectrometric workflow to promote proteomic studies of bone. This workflow uses highly specialized steps, including extensive overnight demineralization, pulverization, and incubation for 72 h in 6 M guanidine hydrochloride and EDTA, followed by proteolytic digestion. Analysis on a high-resolution Orbitrap Eclipse and Orbitrap Exploris 480 mass spectrometer using Data-Independent Acquisition (DIA) provides deep coverage of the bone proteome, and preserves post-translational modifications, such as hydroxyproline. A spectral library-free quantification strategy, directDIA, identified and quantified over 2,000 protein groups (with ≥ 2 unique peptides) from calcium-rich bone matrices. Key components identified were proteins of the extracellular matrix (ECM), bone-specific proteins (e.g., secreted protein acidic and cysteine rich, SPARC, and bone sialoprotein 2, IBSP), and signaling proteins (e.g., transforming growth factor beta-2, TGFB2), and lysyl oxidase homolog 2 (LOXL2), an important protein in collagen crosslinking. Post-translational modifications (PTMs) were identified without the need for specific enrichment. This includes collagen hydroxyproline modifications, chemical modifications for collagen self-assembly and network formation. Multiple senescence factors were identified, such as complement component 3 (C3) protein of the complement system and many matrix metalloproteinases, that might be monitored during age-related bone disease progression. Our innovative workflow yields in-depth protein coverage and quantification strategies to discover underlying biological mechanisms of bone aging and to provide tools to monitor therapeutic interventions. These novel tools to monitor the bone proteome open novel horizons to investigate bone-specific diseases, many of which are age-related.

Hydroxyapatite-Coated Small Intestinal Submucosa Membranes Enhanced Periodontal Tissue Regeneration through Immunomodulation and Osteogenesis via BMP-2/Smad Signaling Pathway.

Periodontitis, a chronic infection causing periodontal tissue loss, may be effectively addressed with in situ tissue engineering. Small intestinal submucosa (SIS) offers exceptional biocompatibility and biodegradability but lacks sufficient osteoconductive and osteoinductive properties. This study develops and characterizes SIS coated with hydroxyapatite (SIS-HA) and gelatin methacrylate hydroxyapatite (SIS-Gel-HA) using biomineralization and chemical crosslinking. The impact on periodontal tissue regeneration is assessed by evaluating macrophage immune response and osteogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro and rat periodontal defects in vivo. The jejunum segment, with the highest collagen type I content, is optimal for SIS preparation. SIS retains collagen fiber structure and bioactive factors. Calcium content is 2.21% in SIS-HA and 2.45% in SIS-Gel-HA, with no significant differences in hydrophilicity, physicochemical properties, protein composition, or biocompatibility among SIS, SIS-HA, SIS-Gel, and SIS-Gel-HA. SIS is found to upregulate M2 marker expression, both SIS-HA and SIS-Gel-HA enhance the osteogenic differentiation of PDLSCs through the BMP-2/Smad signaling pathway, and SIS-HA demonstrates superior in vitro osteogenic activity. In vivo, SIS-HA and SIS-Gel-HA yield denser, more mature bones with the highest BMP-2 and Smad expression. SIS-HA and SIS-Gel-HA demonstrate enhanced immunity-osteogenesis coupling, representing a promising periodontal tissue regeneration approach.

Characterization of rat vertebrae cortical bone microstructures using confocal Raman microscopy combined to tomography and electron microscopy

BackgroundThe rat vertebrae is a good model to study bone regeneration after implantation of biomaterials used to treat bone loss, a major problem in oral and dental surgery. However, the precise characterization of bone microstructures in the rat vertebrae has not been reported. Therefore, the aim of this study was to achieve the complete analysis of such bone, at different scales, in order to have a clear model of healthy bone for comparison with regenerated bone. MethodsIn order to image the cortical bone of rat caudal vertebra, confocal Raman microscopy was combined with high resolution X-ray micro computed tomography (micro-CT), with scanning electron microscopy (SEM) using backscatter electron imaging and with more conventional histology coloration techniques. SEM and Raman microscopy were done in various regions of the cortical bone corresponding to external, middle and internal areas. The spongy bone was imaged in parallel. Micro-CT was performed on the whole vertebra to monitor the network of haversian canals in the cortical bone. Osteonic canals characteristics, and relative chemical composition were analysed in several regions of interest, in cortical and spongy bone. Five rats were included in this study. ResultsOn micro-CT images, differences in intensity were observed in the cortical bone, substantiated by SEM. Chemical analysis with Raman spectra confirmed the difference in composition between the different regions of the cortical and spongy bone. PCA and k-mean cluster analysis separated these groups, except for the external and middle cortical bone. Peak intensity ratio confirmed these results with a CO3 to ν2 PO4 ratio significantly different for the internal cortical bone. Grayscale images stack extracted from micro-CT showed that global architecture of cortical bone was characterized by a dense and complex network of haversian osteonic canals, starting from the surface towards the vertebrae center. The mean diameter of the canals was 18.4 µm (SD 8.6 µm) and the mean length was 450 µm (SD 152 µm). Finally, Raman reconstructed images of the lamellar bone showed an enlargement of the lamellar layer width, both in circumferential lamellar bone and around haversian canals. ConclusionsMicro-CT and confocal Raman microscopy are good tools to complete classical analysis using optical and electron microscopy. The results and measurements presented in a rat model known for its small inter-individual differences provide the main characteristics of a mature bone. This study will allow the community working on this rat vertebrate model to have a set of characteristics, in particular on the structure of the haversian canals.

Formation process of extension knee joint contracture following external immobilization in rats.

Current research lacks a model of knee extension contracture in rats. To elucidate the formation process of knee extension contracture. We developed a rat model using an aluminum external fixator. Sixty male Sprague-Dawley rats with mature bones were divided into the control group (n = 6) and groups that had the left knee immobilized with an aluminum external fixator for 1, 2, and 3 d, and 1, 2, 3, 4, 6, and 8 wk (n = 6 in each group). The passive extension range of motion, histology, and expression of fibrosis-related proteins were compared between the control group and the immobilization groups. Myogenic contracture progressed very quickly during the initial 2 wk of immobilization. After 2 wk, the contracture gradually changed from myogenic to arthrogenic. The arthrogenic contracture progressed slowly during the 1st week, rapidly progressed until the 3rd week, and then showed a steady progression until the 4rd week. Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time. Correspondingly, the level of transforming growth factor beta 1 (TGF-β1) and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2) in the anterior joint capsule also increased with the immobilization time. Over time, the cross-sectional area of muscle fibers gradually decreased, while the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was increased. Unexpectedly, the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was decreased during the late stage of immobilization (6-8 wk). The myogenic contracture was stabilized after 2 wk of immobilization, whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk. This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.

Osseointegration effects of whey protein (histological and histomorphological observations): An experimental study on rabbits

Background: Whey protein is the green-yellow colored, liquid portion of the milk, and it is also called the cheese serum, it is obtained after the separation of curd, during the coagulation of the milk. It contains a considerable amount of α-helix pattern with an evenly distributed hydrophobic and hydrophilic as well as basic and acidic amino acids along with their polypeptide chain. The major whey protein constituents include β-lactoglobulin (β-LG),α-lactalbumin (α-LA), immunoglobulins (IG), bovine serum albumin (BSA), bovine lactoperoxidase (LP), bovine lactoferrin (BLF) and minor amounts of a glycol macro peptide (GMP). Osseointegration can be defined as a process that is immune driven which leads to the formation of the new bone surrounding the surface of the implant rather than a pure response of the bone. Titanium can activate a balance recognized to be tolerogenic with a peri-implant tissue leading to a "foreign body equilibrium (FBE)" response. Materials and methods: Twelve adult male white New Zealand healthy rabbits were used in this study, the animals were divided into two groups according to the time of scarification as follows; 2 and 6 weeks after the implantation (6 rabbits will be sacrificed for each group). Results: Statistical analysis showed that there is a highly significant difference in all parameters between the experimental group and control group at 2 weeks and 6 weeks periods. Histological results at 2 weeks period showed thread formation in whey protein and control group, distribution of osteocyte cells and osteoblast was higher in whey protein, and the bone trabecular area was also larger in whey protein groups but at 6 weeks showed mature bone in whey protein groups while in control group still woven bone. Conclusions: Whey protein is an effective in osseointegration because it enhances bone formation.

The effect of medical biodegradable magnesium alloy in vivo degradation and bone response in a rat femur model with long-term fixation.

It is of great significance to understand the effect of the different corrosion behaviors of magnesium (Mg) alloys manufactured using different casting methods and implanted with different methods on the long-term implantation to expand the application of Mg-based biomedical implants. The effects of four different casting and rolling speeds on the microstructure of an Mg-rare earth (Mg-Re) alloy were analyzed using electron backscatter diffraction (EBSD). Four Mg alloys were obtained using vertical two-roll casting (TRC) at 10m/min, 16m/min, 24m/min, and 30m/min, and their microstructure, corrosion behavior and bone reaction in vivo were studied. The corrosion resistance of the alloy increases with an increase in casting speed and finer grain size of the cast-rolled parts. The Mg-Re alloys with TRC-10m/min and TRC-30m/min were selected for animal experiments. The two Mg alloys were made into metal rods and inserted into the rat femur to simulate the effect of Mg-Re on femoral healing under an injury condition. The rods were implanted for a long time to judge the effects of the Mg-Re alloy on the body. The TRC-30m/min implants obtained highly mature new bone tissue in the case of bone injury. The in vivo experiments showed that the corrosion resistance of the TRC-30m/min implant was better than that of the TRC-10m/min implant. After 32 weeks of implantation, there were no pathological changes in the liver, heart, or kidney of rats in the TRC-30m/min group, and the cell structure was normal.

African swine fever virus MGF360-9L promotes viral replication by degrading the host protein HAX1

African swine fever virus (ASFV) infection causes African swine fever (ASF), a virulent infectious disease that threatens the safety of livestock worldwide. Studies have shown that MGF360–9 L is important for the virulence of ASFV and the host protein HS1-associated protein X-1 (HAX1) plays an important role in viral pathogenesis. This study aimed to clarify the mechanism by which HAX1 mediates ASFV replication through interactions with MGF360–9 L. The regions of interaction between MGF360–9 L and HAX1 were predicted and validated. HAX1 overexpression and RNA interference studies revealed that HAX1 is a host restriction factor that suppresses ASFV replication. Moreover, HAX1 expression was inhibited in ASFV-infected mature bone marrow–derived macrophages, and infection with the virulent MGF360–9 L gene deletion strain (∆MGF360–9 L) attenuated the inhibitory effect of the wild-type strain (WT) on HAX1 expression, suggesting a complex regulatory relationship between MGF360–9 L and HAX1. Furthermore, the E3 ubiquitin ligase RNF114 interacted with MGF360–9 L and HAX1, MGF360–9 L degraded HAX1 through the ubiquitin–proteasome pathway, and RNF114 facilitated the degradation of HAX1 by MGF360–9L-linked K48 ubiquitin chains through the ubiquitin–proteasome pathway, thereby facilitating ASFV replication. In conclusion, this study has enriched our understanding of the regulatory networks between ASFV proteins and host proteins and provided a reference for investigation into the pathogenesis and immune escape mechanism of ASFV.

Osseointegrability of 3D-printed porous titanium alloy implant on tibial shaft bone defect in rabbit model.

Previous studies have demonstrated the ability of osseointegration of porous titanium implants in cancellous bone. Our study was designed to (i) investigate the ability of bone ingrowth into 3D-printed porous titanium alloy implant on the cortical bone of rabbits using CT-scan and histology, and (ii) to identify the consistency of the radiology information between clinical Cone Beam Computed Tomography (CBCT) and Micro Computed Tomography (μCT) in the evaluation of bone ingrowth. The porous titanium alloy implants were 3D-printed employing the Electron Beam Melting (EBM) technology with an intended pore size of 600 μm and porosity of approximately 50 percent. Each implant was inserted into tibial diaphysis in one rabbit and its pores were classified as contacting bone or non-contacting bone. Depending on the time of explantation, the rabbits were divided into two groups: group 1 consisting of 6 rabbits between 13 and 20 weeks and group 2 consisting of 6 rabbits between 26 and 32 weeks. Tissue ingrowth into the non-bone contacting pores were evaluated by CBCT and histology. μCT was used to further investigate the bone ingrowth into four implants (two from each group were randomly chosen). The CBCT detected the present of tissue with bone-like density in both bone-contacting pores and non-bone-contacting pores of all implants. The μCT analysis also supported this result. All the bone-like tissues were then histologically confirmed to be mature bone. The analysis of CBCT data to assess bone ingrowth in porous implants had the sensitivity, specificity, positive and negative predictive values of 85, 84, 93 and 70 percent, respectively, when considering μCT assessment as the gold standard. Fully porous titanium alloy implant has great potential to reconstruct diaphyseal bone defect due to its good ability of osseointegration. CBCT is a promising method for evaluation of bone ingrowth into porous implants.

A Novel Method for Assessing the 3-dimensional Morphology of Cartilaginous Acetabulum Via Childhood Magnetic Resonance Imaging.

Periarticular cartilage is abundant in children, making evaluations of 3-dimensional (D) cartilaginous acetabular morphology using x-ray or computed tomography (CT) difficult. The study aimed to visualize the 3D cartilaginous acetabular morphology in normal children and patients with pediatric developmental dysplasia of the hip (DDH). Magnetic resonance imaging (MRI) of 17 female children without acetabular dysplasia at 7.5 years and CT of 33 normal female adolescents with mature bones at 14.6 years were used as controls. Subjects were 26 female patients with unilateral DDH who underwent angulated Salter innominate osteotomy (A-SIO) at 5.5 years. Preoperative and postoperative MRIs were performed at 5.2 and 7.0 years, respectively. The MRI sequence was 3D-MEDIC. The medial intersection (point A) of the line connecting the centers of the bilateral femoral head and the femoral head were defined as point zero. The 3D coordinates (X, Y, Z) of the cartilaginous acetabular edge (point C) from anterior to posterior were calculated. Subsequently, a 3D scatter plot was created using 3D graph software. The subjects were divided into 6 groups, including control MRI, control CT, unaffected DDH before and after A-SIO, and affected DDH before and after A-SIO. The femoral head coverage ratio (FHCR: AC/AB) was used to quantify coverage and was compared in each group. In the control MRI group, the acetabular coverage was small anteriorly, largest anterolaterally, and gradually decreased posteriorly, similar to the bony acetabulum in adolescents. In the affected DDH before A-SIO group, the coverage was significantly lower than that of the control MRI and unaffected DDH groups. After A-SIO, the morphology improved beyond the unaffected DDH and the control MRI group. The global defect of the cartilaginous acetabulum in the affected DDH group was significantly improved to normal morphology after A-SIO. Evaluating the cartilaginous acetabulum using MRI was useful for assessing hip morphology in childhood. Level III-retrospective comparative study.

An engineered lamellar bone mimicking full-scale hierarchical architecture for bone regeneration

Lamellar bone, compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales, is the structural motif of mature bone. Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone. Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge. Herein, using bioskiving and mineralization, we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone. Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving, the hierarchical mimicry and hierarchy-property relationship are elucidated. With prolongation of mineralization, hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner, i.e. first rising and then descending, which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization. Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis. Bioinformatic analysis further reveals that this construct potently activates integrin α5-PI3K/AKT signaling pathway through mechanical and biophysical cues, and thereby repairing critical-sized bone defect. The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue, and offers a critical research model for in-depth studying the structure-function relationship of bone.

Electron Microscopy (EM) Analysis of Collagen Fibers in the Peri-Implant Soft Tissues around Two Different Abutments.

The design of the implant prosthesis-abutment complex appears crucial for shaping healthy and stable peri-implant soft tissues. The aim of the present animal study was to compare two implants with different healing abutment geometries: a concave design (TEST) and a straight one (CTRL). Transmission electron microscopy (TEM) was used to quantify the three-dimensional topography and morphological properties of collagen at nanoscale resolution. 2 swine were included in the experiment and 6 implants per animal were randomly placed in the left or right hemimandible in either the physiologically mature bone present between the lower canine and first premolar or in the mandibular premolar area, within tooth extraction sites. Each CTRL implant was positioned across from its respective TEST implant on the other side of the jaw. After 12 weeks of healing, 8 specimens (4 CTRL and 4 TEST) were retrieved and prepared for histological and TEM analysis. The results showed a significantly higher percentage of area covered by collagen bundles and average bundle size in TEST implants, as well as a significant decrease in the number of longitudinally oriented bundles with respect to CTRL implants, which is potentially due to the larger size of TEST bundles. These data suggest that a concave transmucosal abutment design serves as a scaffold, favoring the deposition and growth of a well-organized peri-implant collagen structure over the implant platform in the early healing phase, also promoting the convergence of collagen fibers toward the abutment collar.

Three-Dimensional Printing of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] Biodegradable Scaffolds: Properties, In Vitro and In Vivo Evaluation.

The results of constructing 3D scaffolds from degradable poly(3-hydrosbutyrpate-co-3-hydroxyvalerate) using FDM technology and studying the structure, mechanical properties, biocompatibility in vitro, and osteoplastic properties in vivo are presented. In the process of obtaining granules, filaments, and scaffolds from the initial polymer material, a slight change in the crystallization and glass transition temperature and a noticeable decrease in molecular weight (by 40%) were registered. During the compression test, depending on the direction of load application (parallel or perpendicular to the layers of the scaffold), the 3D scaffolds had a Young's modulus of 207.52 ± 19.12 and 241.34 ± 7.62 MPa and compressive stress tensile strength of 19.45 ± 2.10 and 22.43 ± 1.89 MPa, respectively. SEM, fluorescent staining with DAPI, and calorimetric MTT tests showed the high biological compatibility of scaffolds and active colonization by NIH 3T3 fibroblasts, which retained their metabolic activity for a long time (up to 10 days). The osteoplastic properties of the 3D scaffolds were studied in the segmental osteotomy test on a model defect in the diaphyseal zone of the femur in domestic Landrace pigs. X-ray and histological analysis confirmed the formation of fully mature bone tissue and complete restoration of the defect in 150 days of observation. The results allow us to conclude that the constructed resorbable 3D scaffolds are promising for bone grafting.

Advanced Skeletal Ossification Is Associated with Genetic Variants in Chronologically Young Beef Heifers.

Osteogenesis is a developmental process critical for structural support and the establishment of a dynamic reservoir for calcium and phosphorus. Changes in livestock breeding over the past 100 years have resulted in earlier bone development and increased physical size of cattle. Advanced skeletal maturity is now commonly observed at harvest, with heifers displaying more mature bone than is expected at 30 months of age (MOA). We surmise that selection for growth traits and earlier reproductive maturity resulted in co-selection for accelerated skeletal ossification. This study examines the relationship of single nucleotide polymorphisms (SNPs) in 793 beef heifers under 30 MOA with USDA-graded skeletal maturity phenotypes (A-, B-, C- skeletal maturity). Further, the estrogen content of FDA-approved hormonal implants provided to heifers prior to harvest was evaluated in association with the identified SNPs and maturities. Association tests were performed, and the impact of the implants were evaluated as covariates against genotypes using a logistic regression model. SNPs from the ESR1, ALPL, PPARGC1B, SORCS1 genes, and SNPs near KLF14, ANKRD61, USP42, H1C1, OVCA2, microRNA mir-29a were determined to be associated with the advanced skeletal ossification phenotype in heifers. Higher dosage estrogen implants increased skeletal maturity in heifers with certain SNP genotypes.

Bone-Targeted Delivery of Cell-Penetrating-RUNX2 Fusion Protein in Osteoporosis Model.

The onset of osteoporosis leads to a gradual decrease in bone density due to an imbalance between bone formation and resorption. To achieve optimal drug efficacy with minimal side effects, targeted drug delivery to the bone is necessary. Previous studies have utilized peptides that bind to hydroxyapatite, a mineral component of bone, for bone-targeted drug delivery. In this study, a hydroxyapatite binding (HAB) tag is fused to 30Kc19α-Runt-related transcription factor 2 (RUNX2) for bone-targeting. This recombinant protein can penetrate the nucleus of human mesenchymal stem cells (hMSCs) and act as a master transcription factor for osteogenesis. The HAB tag increases the binding affinity of 30Kc19α-RUNX2 to mineral deposition in mature osteoblasts and bone tissue, without affecting its osteogenic induction capability. In the osteoporosis mouse model, intravenous injection of HAB-30Kc19α-RUNX2 results in preferential accumulation in the femur and promotes bone formation while reducing toxicity in the spleen. These findings suggest that HAB-30Kc19α-RUNX2 may be a promising candidate for bone-targeted therapy in osteoporosis.

Osteoma

Osteoma is a benign osteoblastic mesenchymal tumor consisting of differentiated mature bone tissue. Ear canal osteoma is an osteoma that occurs in the external acoustic canal. Osteoma of the ear canal is usually asymptomatic, but several symptoms that can accompany a total occlusion of the external acoustic canal are vertigo, tinnitus, which can also cause recurrent otitis externa, otorrhoea and otalgia. Mr. S came to the ENT Poly at Cut Meutia Hospital with complaints that his left ear felt blocked since 1 year ago. hearing loss in left ear. Left ear often bleeds when prying. Sometimes the patient feels pain in the left ear, and a clear, odorless discharge comes out of the left ear. The patient's left ear is often buzzing.&#x0D; On examination the local physical status found a solid mass, immobile, stalked, and unilateral and had closed all of the left external auditory canal. The tuning test found conductive deafness in the left ear. The patient was planned for CT-Scan Mastoid and osteoma excision surgery.