Osteoid Tissue Research Articles

Histological evaluation of the effects of bone morphogenetic protein 9 and angiopoietin 1 on bone healing

ObjectivesBone healing remains a critical clinical orthopedic problem. Bone, which is a greatly vascularized tissue, depends on the tight temporal and spatial link between blood vessels and bone cells. Thus, angiogenesis is crucial for skeletal growth and bone fracture healing. The purpose of this study was to evaluate the efficacy of the local application of osteogenic and angiogenic factors such as bone morphogenetic protein 9 (BMP9) and angiopoietin 1 (Ang1), respectively, and their combination as an osteoinducer in the process of bone healing. MethodsForty-eight male albino rats, weighing 300–400 g and aged 6–8 months, were utilized in this study. The animals underwent surgery on the medial side of the tibia bone. In the control group, an absorbable hemostatic sponge was locally applied to the bone defect, while experimental groups were separated into three groups. In Group I, 1 mg BMP9 was locally applied, Group II was treated with 1 mg Ang1, and Group III was treated with local application of a combination (0.5 mg BMP9 and 0.5 mg Ang1). All experimental groups were fixed with an absorbable hemostatic sponge. The rats were sacrificed on days 14 and 28 after surgery. ResultsLocal application of BMP9 alone, Ang1 alone, and their combination to a tibia defect caused osteoid tissue formation and significantly increased the number of bone cells. A gradual decrease in the number of trabecular bone, an increase in trabecular area, and no significant difference in the bone marrow area were noted. ConclusionThe combination of BMP9 and Ang1 has therapeutic potential in promoting the healing process of bone defects. Osteogenesis and angiogenesis are regulated by BMP9 and Ang1. These factors act together to accelerate bone regeneration more efficiently than either factor alone.

The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis.

Alginate (ALG) is a biocompatible and biodegradable polymer. Mechanical weakness is one of the main problems for the alginate-based scaffolds. Various plasticizer additives or modifications tested to improve the mechanical properties. In the presented study, ALG plasticized with triacetin (TA), and tributyl citrate (TBC) than tested on bone healing. In the presented study, the alginate modified with triacetin or tributyl citrate. In-vitro, and in-vivo efficiency of the scaffolds tested on bone tissue regeneration. Scaffolds fabricated by solvent casting, and physicochemical characterizations performed. Monocytes (THP-1) cultured with scaffolds, and macrophage-released cytokines was determined. In-vivo efficacy of the scaffolds was tested in the rat drill hole model. Alginate and tributyl citrate-modified scaffolds have no cytotoxic effect on osteoblastic cells (MC-3T3). Tributyl citrate modification increased tumor necrosis factor-alpha (TNF-alpha) level but did not increase interleukin -1 beta (IL-1 beta) level. In vivo studies showed that osteoblastic growth was significant in alginate and triacetin-modified scaffolds. However, the best values for osteoclastic activity and osteoid tissue formation seen in the triacetin modification. The results demonstrated that the modified alginate scaffolds were more successful than non-modified alginate scaffolds and can used as long-term bone repairing treatments.

USP6-associated soft tissue tumors with bone metaplasia: Clinicopathologic and genetic analysis and the identification of novel USP6 fusion partners.

Among those tumors with consistent USP6 rearrangement, some arise from soft tissue and show bone metaplasia, including myositis ossificans (MO), fibro-osseous pseudotumor of digits (FOPD), soft tissue aneurysmal bone cyst (ST-ABC) and fasciitis ossificans (FO). These lesions are easily confused with malignancies because they show a rapid growth rate and brisk mitoses. Here, we aim to clarify the clinicopathologic and genetic characteristics of this entity and analyze the correlations among the different subtypes in one of the largest cohorts. The clinicopathologic features of 73 cases of MO, FOPD, ST-ABC and FO diagnosed at West China Hospital, Sichuan University from January 2010 to December 2021 were retrospectively analyzed. Forty-three undecalcified samples were analyzed by systematic genetic studies, including fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), Sanger sequencing and next-generation-based sequencing were performed. This series included 40 males and 33 females aged 2 to 80 years old (median: 31 years). FOPD occurred in extremal soft tissue, while lower extremities (38/58, 65.5%) were the most commonly involved lesions in the other three subgroups. Histologically, proliferative myofibroblasts/fibroblasts with varying degrees of osteoid tissue were present. Fluorescence in situ hybridization (FISH) results indicated that 22 cases (22/27, 81.5%) were positive for USP6 rearrangement, and 5 cases were negative. Among those cases with positive FISH results, 18 underwent reverse transcription-polymerase chain reaction (RT-PCR) detection that successfully detected common USP6 fusion types. Thirteen cases showed COL1A1::USP6 fusion, one showed MYH9::USP6 fusion, and 4 were negative for common fusion types. Next-generation-based sequencing technology was performed on two lesions with negative RT-PCR results and novel fusion partners SNHG3 and UBE2G1 were discovered. Our findings revealed that COL1A1 is the most common fusion partner in this entity, unlike primary aneurysmal bone cysts and nodular fasciitis. Notably, we believed that FO may demonstrate more similar clinicopathologic and genetic manifestations with MO/FOPD and ST-ABC instead of nodular fasciitis for involving lower limbs most frequently and showing recurrent COL1A1::USP6 fusion. Additionally, this study also found two novel USP6 fusion partners, which further expanded our knowledge of this neoplastic spectrum.

The Effect of Human Demineralized Dentin Matrix Scaffold Alone and Combined with Concentrated Growth Factor on Bone Repair in Rabbits

Purpose: This study aimed to evaluate the potential effect of Human Demineralized Dentin Scaffold (HDDS) alone and when combined with Concentrated Growth Factor (CGF) on repair of bony defects in the tibia of rabbits, histologically, by using scanning electron microscope and computed tomography. Materials and Methods: Ten adult male rabbits (weight 2 to 2.5 kg) were used in this study. Ethics committee approval of Faculty of Dental Medicine For Girls as obtained with code number (REC-BI-19-01). In each rabbit two holes were created (one in each tibia). In five rabbits, the first control hole was left empty and the second was packed with CGF. In the other five rabbits, one hole was packed with DDM slices from anonymous human permanent teeth without carious lesion or other pathology and the second was packed with DDM and CGF. The rabbits were euthanized at 1 and 6 weeks postoperatively and the bone samples were processed for histological analysis. Results: Faster bone repair was occurred in the experimental groups. In all groups, Osteoid tissue formation was occurred at one week, and osseous tissue formation was seen filling the bone defects at 6 weeks. The best results after 6 weeks appeared in surgical bone defects grafted with HDDS and CGF where the new bone showed better organization than the HDDS alone and CGF alone and most of the formed osteons were fully compacted. Conclusion: Combining Human Demineralized Dentin Scaffold (HDDS) with concentrated growth factor (CGF) improved graft biomaterial when used as xenograft and it became more effective through inducing a faster bone repair.

LONG NON-CODING RNAs AND AUTOPHAGY IN OSTEOSARCOMA

Osteosarcoma (OSA) is an aggressive bone tumor that occurs primarily in children and adolescents worldwide, with a high metastatic and recurrence ability. OSA is characterized by the transformation of mesenchymal cells and the formation of osteoid tissue. Although recent advancements have improved the current therapeutic management of OSA, the clinical outcomes of the disease still remain unsatisfactory. Therefore, it is important to determine the novel diagnostic markers and/or therapeutic targets for OSA. Autophagy is a highly conserved self-degradative process that plays a crucial role in various physiological mechanisms such as survival, homeostasis, development and differentiation. Dysfunction of autophagy is the relationship with the onset and development of several types of cancer, including OSA. Long non-coding ribonucleic acids (lncRNAs), a group of non-coding RNAs, regulate various pathophysiological mechanisms such as inflammation, autophagy and apoptosis. Recent studies investigating the role of lncRNAs in the pathogenesis of OSA have shown that these molecules might have diagnostic and therapeutic importance for the prevention of OSA. Here, we focus on lncRNAs that modulate autophagy in OSA and discuss the potential clinical values of lncRNAs for OSA. The current study contributes to a better understanding of OSA pathogenesis and to the development of novel therapeutic approaches for the prevention of OSA.

Shilajit potentiates the effect of chemotherapeutic drugs and mitigates metastasis induced liver and kidney damages in osteosarcoma rats

Osteosarcoma is a primary malignant cancer of the bone identified by the direct formation of osteoid tissue or immature bone by cancer cells. The liver and kidneys represent two major secondary organs to which osteosarcoma metastasizes. In this study, we assessed Shilajit, a phytomineral diffusion traditionally used in Ayurvedic medicine, for its possible protective effects against metastasis induced liver and kidney damages in an osteosarcoma rat model. Osteosarcoma rats displayed typical dysregulation of serum levels of hepatic and renal functional markers (p < 0.05) including aspartate aminotransferase (AST)* and alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins, albumin, bilirubin, creatinine, urea, and uric acid. Changes in functional markers were also positively correlated with marked histopathological alterations in liver and kidney tissues. Whereas Shilajit's treatment of osteosarcoma rates in combination with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy drug cocktail significantly (p < 0.05) reversed the studied functional markers to their near-normal levels. Co-treatment of shilajit and drug cocktails also markedly alleviated histopathological changes in liver and kidney tissues. Correlation co-efficient analysis of hepatic and renal functional markers revealed a significant inter-association among these markers. Collectively, present data indicate that shilajit may potentiate the effects of chemotherapy drugs and mitigate the metastasis-induced liver and kidney damage in osteosarcoma. Thus, the findings of this study substantiate the beneficial health effects of shilajit and promote its regular consumption.

Enhancement of critical-sized bone defect regeneration using UiO-66 nanomaterial in rabbit femurs

BackgroundRepair of large-sized bone defects is a challengeable obstacle in orthopedics and evoked the demand for the development of biomaterials that could induce bone repair in such defects. Recently, UiO-66 has emerged as an attractive metal–organic framework (MOF) nanostructure that is incorporated in biomedical applications due to its biocompatibility, porosity, and stability. In addition, its osteogenic properties have earned a great interest as a promising field of research. Thus, the UiO-66 was prepared in this study and assessed for its potential to stimulate and support osteogenesis in vitro and in vivo in a rabbit femoral condyle defect model. The nanomaterial was fabricated and characterized using x-ray diffraction (XRD) and transmission electron microscopy (TEM). Afterward, in vitro cytotoxicity and hemolysis assays were performed to investigate UiO-66 biocompatibility. Furthermore, the material in vitro capability to upregulate osteoblast marker genes was assessed using qPCR. Next, the in vivo new bone formation potential of the UiO-66 nanomaterial was evaluated after induction of bone defects in rabbit femoral condyles. These defects were left empty or filled with UiO-66 nanomaterial and monitored at weeks 4, 8, and 12 after bone defect induction using x-ray, computed tomography (CT), histological examinations, and qPCR analysis of osteocalcin (OC) and osteopontin (OP) expressions.ResultsThe designed UiO-66 nanomaterial showed excellent cytocompatibility and hemocompatibility and stimulated the in vitro osteoblast functions. The in vivo osteogenesis was enhanced in the UiO-66 treated group compared to the control group, whereas evidence of healing of the treated bone defects was observed grossly and histologically. Interestingly, UiO-66 implanted defects displayed a significant osteoid tissue and collagen deposition compared to control defects. Moreover, the UiO-66 nanomaterial demonstrated the potential to upregulate OC and OP in vivo.ConclusionsThe UiO-66 nanomaterial implantation possesses a stimulatory impact on the healing process of critical-sized bone defects indicating that UiO-66 is a promising biomaterial for application in bone tissue engineering.

Endolymphatic sac tumour: exploring the role of CT and MRI features in the diagnosis of 22 cases

To explore the role of imaging features in the diagnosis of endolymphatic sac tumour (ELST). Twenty-two patients with ELST confirmed at histopathology were included in this retrospective study. All patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations, including diffusion-weighted imaging (DWI; n=18) and dynamic contrast-enhanced (DCE) MRI (n=3). The imaging features of this series were analysed. All lesions appeared as irregular soft-tissue mass lesions located in the middle and posterior margin of the petrous bone. At CT, the normal vestibular aqueduct structure disappeared. Multiple osteoid tissues were present inside the tumour, and destructive bone changes had a "honeycomb" pattern. Twenty cases were accompanied by the incomplete thin bony peripheral rim along the medial margin. On both T1-weighted imaging (WI) and T2WI, all lesions showed hyperintense, hypointense, and isointense mixed signal intensity. Scattered peripheral hyperintensities were found in all cases on T1WI. The mean apparent diffusion coefficient (ADC) value of 18 lesions was (1.35±0.13)×10-3 mm2/s, which was similar to that of masseter muscles. On enhanced T1WI, all lesions had significant heterogeneous enhancement, and the vascular flowing-void effect was seen in larger lesions (≥1.5 cm). The time-signal intensity curve (TIC) showed a plateau type in all three cases. The imaging features of ELST, including its location, bone destruction form, MRI signal intensity, and enhancement pattern, are helpful to improve the diagnostic accuracy of this rare tumour.

Bimodal coarse-grained and unimodal ultrafine-grained biodegradable Zn-0.5Mn alloy: Superplastic mechanism and short-term biocompatibility in vivo

Bimodal coarse-grained (BCG) and unimodal ultrafine-grained (UUFG) Zn-0.5Mn alloys were prepared in this paper, and the mean grain sizes under two different conditions were approximately 1.20 and 0.40 µm, respectively. The remarkable difference in the microstructure of BCG and UUFG led to a substantial increase in ductility, and the latter’s maximum elongation-to-failure reached 266.2% ± 8.3% at room temperature (RT). Analysis of the microstructural features of the broken tensile sample longitudinal section showed that different from BCG, the grain size of UUFG sample decreased gradually from distal to proximal fracture. It also showed a marked grain elongation (growth) because ultrafine grains rotate during plastic deformation and could coalesce along the directions of shear, creating larger paths for dislocation movement, which may be the most important facts of obtaining RT superplasticity. The MnZn13 particles in UUFG had enhanced grain refining efficiency during uniaxial tension compared with those in BCG. Thus, UUFG microstructure remarkably increased the plasticity of Zn-0.5Mn alloy while the suitable temperature region for superplastic deformation was low, which is important for practical application. The investigation of short-term biocompatibility in vivo revealed that the bone biocompatibility of UUFG was quite good, which could induce early osteoid tissue deposition, and no distinguishable injury to the structure/function of the liver and the kidney was found.

Perception of Rickets Disease Among Parents in Al-Baha Province, Saudi Arabia

IntroductionRickets involves the softening of bones in children and osteopenia with disordered calcification, leading to a higher proportion of osteoid tissue prior to epiphyseal closure in children. Rickets is common in the Middle East, Africa, and Asia. The peak age of prevalence is 3–18 months. Signs include bone tenderness, easy fracture, early bone deformity, delayed closure of fontanelles, and softening of skull bones (craniotabes).ObjectiveThis study assesses knowledge in the AlBaha region about rickets’ clinical presentation, causes, complications, and prevention, as well recommendations to educate the community.MethodsIn this descriptive cross-sectional study, a questionnaire was administered to people in the AlBaha region to assess knowledge related to rickets in children. The sample size was calculated using calculator.net, and the Statistical Package for Social Sciences (SPSS) version 2 was used for analyses with P < 0.05 used for significance.ResultsOf the 692 participants, only 5% reported rickets in their children, but the majority (99%) had heard about rickets. Participants’ knowledge of rickets’ complications was highest for spinal vertebral deformities and lowest for skin deformities. 55% of the participants thought there was no need to stop breast-feeding once rickets is diagnosed, 62% preferred to add fortified milk to the diet, 67% thought that a suitable duration for sunlight exposure is 10 to 15 minutes per day, and 46% thought that sunrise and sunset are suitable times for sun exposure. Preventive measures were believed to depend on having enough exposure to sunlight (77% of participants) and eating vitamin-D rich foods (63%). The majority believed that failure to grow is the most obvious symptom, inadequate milk is the main cause, and exclusive breast-feeding is a major risk factor.ConclusionMost people have heard about rickets, but knowledge about complications and prevention varies.

Inhibiting Endothelin Receptors with Macitentan Strengthens the Bone Protective Action of RANKL Inhibition and Reduces Metastatic Dissemination in Osteosarcoma.

Simple SummaryThe efficacy of current osteosarcoma therapy is diminished by two adverse events, namely resistance to chemotherapy and metastatic dissemination. In recent decades, research has been devoted to reducing these adverse events. Inhibiting bone resorption has shown promising effects on metastatic dissemination and tumor growth, with, however, the formation of significant tumoral mineralized tissue. Endothelin signaling is implicated in activating the cell that forms the mineralized tissues, consequently the impact of inhibiting it alone and in combination with the inhibition of bone resorption was evaluated using osteosarcoma models. The results obtained showed that inhibiting endothelin signaling significantly reduced the formation of mineralized tumor tissue concomitantly to metastatic dissemination without affecting sensitivity to chemotherapy. This inhibition appears to be a promising new therapeutic tool in the fight against osteosarcoma.Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors.

Ginger and Garlic Extracts Enhance Osteogenesis in 3D Printed Calcium Phosphate Bone Scaffolds with Bimodal Pore Distribution.

Natural medicines have long been used to treat physiological ailments where both ginger (gingerol) and garlic (allicin) are key players in immune system promotion, reduction in blood pressure, and lowering inflammation response. With their efficacy in bone healing, these compounds have great value as medicinal additives in bone scaffolds for localized treatment to support tissue formation, along with providing their natural therapeutic benefits. Utilization of 3D-printed (3DP) bone tissue engineering scaffolds as drug delivery vehicles for ginger and garlic extracts enables patient specificity in bone defect applications with enhanced osseointegration. Our objective is to understand their combined efficacy on osteogenesis when released from 3DP calcium phosphate bone scaffolds designed with a bimodal pore distribution. With a porous core and dense exterior, the resulting scaffolds have good mechanical integrity with 10 ± 1 MPa compressive strengths. Results show that ginger + garlic extracts released from bone scaffolds enhance their osteogenic potential through on site drug delivery. Both compounds exhibit exponential drug release profiles which fit Weibull distribution equations. The release of ginger extract also increases osteoblast proliferation by 59%. Both compounds show decreased osteoclast resorption activity, with a greater than 20% reduction in pit area on sample surfaces. Ginger + garlic extract induces a twofold increase in early osteoid tissue formation in vivo at week 4, in addition to a 30% increase in total bone area and a 90% increase in osteocytes with respect to control 3DP tricalcium phosphate scaffolds. Late-stage bone healing at week 10 reveals healthy angiogenic tissue, a twofold higher bone mineralization, and significant enhancement of type I collagen formation in the presence of ginger and garlic extracts. Naturally sourced ginger and garlic extracts provide osteogenic promotion and improved bone tissue in-growth in a patient-specific 3DP scaffold biomedical device for low load-bearing bone tissue engineering and dental applications.

Role of extracellular vesicles in osteosarcoma.

Osteosarcoma is a malignant bone tumor characterized by the direct production of osteoid tissue from tumor cells. Extracellular vesicles are membranous vesicles released by cells into the extracellular matrix, which exist widely in various body fluids and cell supernatants, and stably carry some important signaling molecules. They are involved in cell communication, cell migration, angiogenesis and tumor cell growth. Increasing evidence has shown that extracellular vesicles play a significant role in osteosarcoma development, progression, and metastatic process, indicating that extracellular vesicles can be use as biomarker vehicles in the diagnosis and prognosis of osteosarcoma. This review discusses the basic biological characteristics of extracellular vesicles and focuses on their application in osteosarcoma.

EXPERIENCE OF USING ENAMEL MATRIX PROTEIN IN COMBINATION WITH A CORONARY ADVANCED FLAP AND A CONNECTIVE TISSUE GRAFT TO ELIMINATE GUM RECESSION

The article presents the experience of complex managing a patient with gum recession in the area of the maxillary premolars. Periodontal treatment of gum recession consisted of initial therapy, including supra- and subgingival scaling, root planing, pharmacotherapeutic support (broad-spectrum antiseptics, drugs that stimulate regeneration), surgical combined method based on the use of enamel matrix protein to stimulate regenerative processes. The clinical material Emdogaine is a combination of an enamel matrix derivative and propylene glycol alginate, which performs the function of a carrier. Biora company has been producing it for more than 20 years (Emdogain, BIORA): now the rights to this material belong to Straumann). This preparation was developed to stimulate regeneration of periodontal tissues. Amelogenin is a specific enamel protein capable of stimulating regeneration of lost periodontal tissues by influencing cell differentiation. Dental cement is an osteoid connective tissue that covers the roots of teeth and serves to attach periodontal fibers. Application of an enamel matrix derivative to the sanitized root surface leads to regeneration of non-cellular cement and to the formation of periodontal tissues, which was observed in our study. Transplantation of free connective tissue grafts to eliminate gum recessions makes it possible to effectively eliminate gum recession in most clinical cases (complete root coverage, an increase in the level of clinical attachment from the keratinized attached gum area). In our clinical case, free grafts were obtained in the donor area of the maxillary tuberosity. Transplantation of free connective tissue grafts provides an aesthetic result and is currently considered a standard technique for eliminating gum recession. According to the clinical study, a combined use of connective tissue grafts and the enamel matrix derivative, an additional use of enamel matrix derivative enabled to obtain a satisfactory result and to improve the appearance of the dentition. Such combined surgeries are indicated in an aesthetically significant area. The described materials, methods and stages of patient's follow up can serve as the basis for the protocol of managing patients with gum recession.

P091 Osteoid osteoma of the trapezoid bone: a diagnostic pitfall of a wrist chronic monoarthritis

Abstract Background Osteoid osteoma is a benign bone tumor representing ∼10% of all benign bone tumors. Although osteoid osteoma of the long bones is usual, the location in the carpus, especially, in the trapezoid bone is rare [1,2]. The Objective is toreport a case of osteoid osteoma of the trapezoid bone with extension to the adjacent second metacarpal bone that was missed diagnosis at initial presentation. Methods We describe the clinical, radiological features and outcomes after surgical resection. Results A 24-year-old right-handed female, presented with a three-year history of pain at the left wrist, particularly, in the radial-side. She didn’t report any trauma to the wrist. The pain increased over time. She couldn’t use her hand in daily activities and could hardly sleep because of increasing pain at night. Before being referred to our department, she consulted a surgeon. She was treated with oral anti-inflammatory drugs, steroids, several intraarticular steroid injections without relieving pain. The Magnetic resonance imaging (MRI) showed bone marrow oedema in the trapezium and the trapezoid bone, synovial effusion, and tenosynovitis of the flexors of the thumb. A synovectomy was performed and the histopathology revealed non-specific chronic inflammation. One year later in our department, examination showed wrist swelling, tenderness and pain on palpation. The erythrocyte sedimentation rate was 12 mm/h and the mean C-reactive protein was 2 mg/l. Autoantibodies testing were negative. Initial radiography was read as normal. Initially, Naproxen (550 mg/day) and Morphine (60 mg/day) were prescribed with partially relieving pain. Scintigraphy showed increased uptake of 99mTc in the radial-side of the left wrist. Then, a bone tumor was suspected. The Computed tomography (CT) images revealed a well-demarcated sclerotic nidus surrounded by a halo of radiolucent osteoid tissue, consistent with an osteoid osteoma of the trapezoid bone and the adjacent second metacarpal bone. Surgical resection of the osteoid osteoma was performed. Histopathological examination confirmed the diagnosis. The patient reported complete pain relief since her surgery. She had no recurrence to date. Conclusion Osteoid osteoma should be in the differential diagnosis list of chronic wrist pain/arthritis. In this case, careful attention is necessary for patients unresponsive to treatment with long-lasting symptoms. If radiographs are inconclusive, CT or MRI should be considered to better visualize the nidus of osteoid osteoma in the small bones of the hand.

Histomorphometric Comparison of New Bone Formed After Maxillary Sinus Lift With Lateral and Crestal Approaches Using Periostal Mesenchymal Stem Cells and Beta-Tricalcium Phosphate: A Controlled Clinical Trial.

The present study investigated clinical and histomorphometric data after sinus lift procedures performed with and without mesenchymal stem cells (MSCs) added to a graft. Twenty-four patients underwent maxillary sinus lift for implant placement. Twelve patients each were assigned to control (Group 1) and test (Group 2) groups. An MSC suspension was added to the graft used in patients of Group 2. Five of 12 patients in both groups underwent crestal-approach sinus lift with immediate implant placement, while seven patients received a lateral-approach sinus lift. The MSC suspension was obtained using the Rigenera protocol. Samples from the grafted site were evaluated, processed, and stained using three staining techniques 90 days after surgery. Histomorphometric analysis was performed using an imaging software (ImageJ). Two types of tissues were defined: Type 1 'mature bone' and Type 2 'osteoid tissue'. The mean Type 1 tissue percentage was 27.24% in Group 1 and 44.45% in Group 2 (P < 0.05). The mean Type 2 tissue percentage was 10.86% and 7.04% in Groups 1 and 2, respectively. The mean Type 1 tissue percentages for the crestal approach were 24.52% for Group 1 and 50.78% for Group 2, while the mean Type 1 tissue percentages for the lateral approach were 29.18% for Group 1 and 39.92% for Group 2. Patients treated with grafts containing MSCs showed 63.18% increased bone formation compared to those treated with grafts not containing MSCs (P < 0.05). Although our data showed a positive trend in patients treated with MSCs, differences between subgroups were not significant (P > 0.05).

Preliminary Histological Evaluation of the Application of Ozone in the First Days of Orthodontic Force Induction in Animal Model.

Objectives The aim of the study was to histologically evaluate the effect of ozone therapy on orthodontic force induction in an animal model. Materials and Methods Twenty-four Wistar rats were divided into three groups ( n = 8). A NiTi coil spring was installed from the maxillary first molar to the maxillary central incisor. G1 was control and G2/G3 received 1 mL of ozonated gas at concentrations of 10 and 60 µg/mL, in the buccal mucosa above the first molar roots. The animals were euthanized 3 and 5 days after the procedure. Histological sections were obtained, longitudinally of the first molar’ long axis, in the mesiodistal direction. The number of osteoclasts, osteoblasts, blood vessels, polymorphonuclear and mononuclear cells, formation of osteoid tissue and hyaline areas, and root resorption were evaluated with light microscope, in tension and pressure sides. Intergroup comparisons were performed with Kruskal–Wallis, Dunn, and Chi-square tests. Results At 3-days pressure side, a greater number of osteoclasts was observed in ozone groups and greater number of blood vessels and polymorphonuclear cells were observed in G2. On the tension side, there was a significantly greater number of blood vessels, osteoblasts, and mononuclear cells in G2. At 5-days pressure side, there was a significantly greater number of osteoclasts in G2, blood vessels and osteoblasts in the ozone groups, and lesser number of polymorphonuclear cells in G3. Conclusion Ozone therapy increased the number of osteoclasts on the pressure side and osteoblasts on tension side, in 10 µg/mL concentration, demonstrating histological parameters favorable to bone remodeling. The 60 µg/mL ozone concentration accelerated the periodontal ligament reorganization process.

Bone regeneration in both small and large preclinical bone defect models using an injectable polymer-based substitute containing hydroxyapatite and reconstituted with saline or autologous blood.

Microbeads consisting of pullulan and dextran supplemented with hydroxyapatite have recently been developed for bone tissue engineering applications. Here, we evaluate the bone formation in two different preclinical models after injection of microbeads reconstituted with either saline buffer or autologous blood. Addition of saline solution or autologous blood to dried microbeads packaged into syringes allowed an easy injection. In the first rat bone defect model performed in the femoral condyle, microcomputed tomography performed after 30 and 60 days revealed an important mineralization process occurring around and within the core of the microbeads in both conditions. Bone volume/total volume measurements revealed no significant differences between the saline solution and the autologous blood groups. Histologically, osteoid tissue was evidenced around and in contact of the microbeads in both conditions. Using the sinus lift model performed in sheep, cone beam computed tomography revealed an important mineralization inside the sinus cavity for both groups after 3months of implantation. Representative Masson trichrome staining images showed that bone formation occurs at the periphery and inside the microbeads in both conditions. Quantitative evaluation of the new bone formation displayed no significant differences between groups. In conclusion, reconstitution of microbeads with autologous blood did not enhance the regenerative capacity of these microbeads compared to the saline buffer group. This study is of particular interest for clinical applications in oral and maxillofacial surgery.

Biological analysis of an innovative biodegradable antibiotic eluting bioactive glass/gypsum composite bone cement for treating experimental chronic MRSA osteomyelitis

A multi-barrier antibiotics loaded biodegradable composite bone cement for resolving chronic osteomyelitis has been studied to understand the physico-mechanical properties, drug loading/eluting efficiency, and different merits and demerits prior to clinical application. After successful induction of bone infection in 28 rabbits using methicillin-resistant Staphylococcus aureus (MRSA) strains, calcium sulfate/bioactive glass based composite cement was implanted in 12 defects to assess its performance over parenteral therapy with microscopic and radiological examination for 90 days. The composite cement revealed acceptable physico-mechanical properties and controlled drug elution kinetics. Furthermore, the antibiotics concentrations in bone up to 42 days were sufficient to kill MRSA without eliciting adverse drug reactions. The striking feature of platelets aggregation by composite cement could assist bone healing. The controlled degradation with simultaneous entrapment of composite cement within the osteoid tissues and complete repair of infected cortical defects (holes) in rabbit tibia at 6 weeks indicated the excellent anti-infective and osteoconductive properties of composite cement. Thus, the animal study demonstrated the superiority of composite over injectable antibiotic therapy based on infection resolution and bone regeneration. We thereby conclude that the composite cement can be effectively applied in the treatment of resistant cases of chronic osteomyelitis.

Technology for Repairing Osteomyelitic Bone Defects Using Autologous Mesenchymal Stromal Cells on a Collagen Matrix in Experiment.

The aim of the study was to develop a technology for repairing an osteomyelitic bone defect using autologous adipose tissue mesenchymal stromal cells (MSCs) bound to a collagen matrix and to test the efficacy of this technique.Materials and Methods.The study was carried out with 17 rabbits. A bone defect was created using a milling cutter applied to the proximal third of the leg. The wound (8.0×4.0 mm and a depth of 4.0 mm) involved the periosteum, cortical layer, and cancellous substance. Staphylococcus aureus strain was used as an infectious agent.After the development of chronic osteomyelitis, the animals underwent osteonecrectomy. In the study group, autologous MSCs in Collatamp EG collagen carrier were placed into the bone defect. MSCs were obtained from adipose tissue and cultured in the matrix for 5 days. In control, the defect was filled with the collagen matrix without cells.Results.On day 14 upon the initiation of chronic osteomyelitis, bacteriological examination of the discharge from the fistula showed the presence of mixed bacterial flora (Staphylococcus aureus and Escherichia coli) in all operated animals. Results of X-ray, laboratory, and histological tests confirmed the formation of a focus of chronic osteomyelitis.Two months after the treatment (collagen with or without MSCs) began, all animals of the study group showed mature bone tissue regenerated in the affected zone. In the control group, proliferation of osteoblasts on the surface of the bone trabeculae was also observed; however, mature osteoid tissue was more often detected in the study group (35.0 vs 20.0% in control). In the study group (MSCs + collagen matrix), there was a decrease in bone marrow fibrosis (50.0 vs 100.0% in control) and cartilage formation (30.0 and 66.7%, respectively). After full treatment, newly formed bone trabeculae were detected more often (100.0 vs 60.0% in control); they were more mature and filled the defect area more efficiently.Conclusion.Our results indicate that the use of a collagen matrix with autologous MSCs is a promising plastic material for repairing osteomyelitic defects following necrectomy.The MSCs were able to increase the density of the filling material in the bone cavity, significantly accelerate the formation of bone beams around the matrix, and increase the tissue volume around the implant. The presence of MSCs significantly decreased the interference of a connective tissue component with osteogenesis and chondrogenesis.