Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 $$\pm $$ ± 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

A Case Report of 41-Year-Old Female with Fibrous Dysplasia Combined with Ethmoid Mucocele

Fibrous dysplasia (FD) is a non-malignant progressive condition, which replaces normal bone and marrow with fibrous tissue and woven bone. Sinus mucocele is a cystic, expansile, and destructive lesion that occurs as a result of obstruction of the sinus ostium secondary to inflammation, trauma, anatomical variation, previous sinus surgery, tumor or FD. Among them, FD combined with mucocele has been rarely reported. Here we report the first case of FD combined with ethmoid mucocele. The patient underwent endoscopic debulking of FD and marsupialization of mucocele. The mucocele was successfully marsupialized, and the patient’s symptoms were completely resolved. We propose a new hypothesis that nasal mucosa invaginates into FD and forms a mucocele. For the treatment of ethmoid FD combined with mucocele, we recommend an endoscopic transnasal approach for debulking and marsupialization.

Post-Denosumab-Treated Giant Cell Tumor of Bone: A Retrospective Histomorphological and Immunohistochemical Study

Introduction Giant cell tumors of bone (GCTBs) are treated with surgery with or without local adjuvants. Denosumab is a human monoclonal antibody that has recently emerged to be effective in treating unresectable and recurrent GCTBs. Objective In this study, we analyzed the histomorphological changes in GCTB following treatment with denosumab. The expression of histone mutation H3.3G34W by immunohistochemistry (IHC) using mutant specific antibody was also determined. Materials and Methods Of the total 109 GCTBs encountered during the study period, 14 cases with neoadjuvant denosumab therapy were analyzed retrospectively. The post-treatment changes on histopathology were examined on routine hematoxylin and eosin-stained sections. IHC was done using antihistone H3.3G34 antibodies. Statistical analysis was limited to descriptive statistics. No hypothesis testing was performed. Results All these cases except three showed fibrosis with areas of hyalinization, prominent newly formed woven bone along with spindle cells in short fascicles and storiform pattern. There was complete absence and marked reduction in osteoclast-like giant cells in six and five patients, respectively. Only three patients showed a substantial amount of residual osteoclast-like giant cells. IHC with antihistone H3.3G34W antibody showed unequivocal nuclear positivity in the mononuclear cells in nine cases. The mononuclear cells rimming and entrapped within the woven bone were also positive on IHC. The spindle cells in the benign fibrous histiocytoma-like areas and septa of aneurysmal bone cyst-like areas also retained nuclear staining. Conclusion Awareness of post-denosumab-related histopathological changes are necessary to avoid misdiagnosis as fibroosseous lesion and low-grade central osteosarcoma. Expression of mutant-specific H3.3 G34W antibody suggests that the neoplastic stromal cells are largely retained after denosumab therapy. The positive staining of cells both within and those rimming the newly formed woven bone point toward osteoblastic phenotype of the neoplastic stromal cells.

Healing Capacity of Bone Surrounding Biofilm-Infected and Non-Infected Gutta-Percha: A Study of Rat Calvaria

This paper aims to evaluate the healing capacity of bony lesions around biofilm-infected and non-infected gutta-percha (GP) points. Bony defects were created in the calvaria of 28 Wistar rats. The rats were divided into three groups: Group 1—Implantation of infected GP particles in the bony defect; Group 2—Positive control implantation of non-infected GP particles in the bony defect; and Group 3—Negative control, in which no GP particles were implanted. The biofilm consisted of three strains of bacteria: Enterococcus faecalis, Streptococcus sanguis, and Porphyromonas gingivalis. The animals were sacrificed 60 days postoperation, and histological assessments were performed. In Group 1, the biofilm-infected group, we observed a mild foreign body reaction with a few inflammatory cells adjacent to the capsule and a newly woven bone matrix surrounded by osteoblasts and mature bone. In Group 2, the non-infected GP particles group, minimal inflammatory cell reactions were observed in the adjacent tissue, and a newly woven bone matrix was surrounded by osteoblasts. This study shows that bone healing is possible around both sterile and infected GP points. This contradicts the claim that some root canal treatments fail because of non-microbial factors, including extruded root canal filling materials, which may cause foreign body reactions. The healing observed suggests that overextension should not be considered an indication for endodontic surgery.

Ridge preservation applying a novel hydrogel for early angiogenesis and osteogenesis evaluation: an experimental study in canine

Ridge preservation is universally acknowledged as the conventional method for the post-extraction healing yet there are no standard materials for the ideal healing outcome. Herein, a composite gel comprising gelatin nanoparticles (GNPs) and injectable platelet-rich-fibrin (i-PRF) as the potential candidate for extracted socket healing is introduced. The combination of GNPs and i-PRF not only possesses favorable mechanical properties to withstand external force but also accelerate the blood clotting time significantly. In addition, six beagle dogs were adopted to assess the angiogenic and osteogenic capacity of GNPs+i-PRF gel in vivo. The GNPs+i-PRF gel significantly produced the most blood vessels area, woven bone and low osteoclast activity in extracted sockets at 2 weeks postoperation and remarkably generated corticalization on the alveolar ridge crest at 8 weeks postoperation according to histological results. Therefore, GNPs+i-PRF gel can be recommended as the candidate grafting material regarding ridge preservation for its cost effectiveness, excellent biocompatibility, facilitation of blood clotting and favorable capacity of promoting angiogenesis and osteogenesis.

Effect of Combined Extracts of Mummy, Withania Coagulans, and Turmeric on the Repair and Treatment of Bone Fractures in Rats

Background: Repair of broken bones due to physiological or pathological factors has always been important for researchers. In this regard, this study aimed to evaluate the effect of a combined extract on the osteogenic process in the experimental fracture created in the femoral of rats as laboratory models. Materials and Methods: This experimental study was performed on 21 rats. After induction of general anesthesia to each mouse, a 3-cm incision was made in the femoral bone and it was broken with a special hammer. After surgery, the control group did not receive any extract, while the three experimental groups received 200, 500, and 1000 mg/kg PO, respectively. In the next step, 21 days after surgery, euthanasia was performed and bone sections were prepared and stained in the fracture site. Next, histopathological and histomorphometric studies were carried out for the evaluation of bone healing in rats. The collected data were analyzed in SPSS software (version 21). Results: According to the pairwise comparison test, the mean difference of variables, namely bone marrow, woven bone, and lamellar bone of the third group of the test was significantly different from those of the other groups (P<0.05). This indicated that receiving the extract in the experimental groups with an increased dose led to a decrease in the mean bone marrow and woven bone which, in turn, increased the mean lamellar bone. Conclusion: The results showed that the combined extracts of mummy, Withania coagulans, and turmeric can stimulate osteogenesis in rats and be considered as a candidate for fracture treatment.

Multi-Modality Imaging of Craniofacial Fibrous Dysplasia with Orbital Complications and Histopathology Correlation-A case report and short review of literature

Craniofacial fibrous dysplasia [CF-FD] with orbital complications is a known but rare entity. This is a multi-modality imaging Case Report of extensive CF-FD in a 31-year-old male with right eye pain, swelling, and redness, along with histopathology correlation. In this patient, the CT scan demonstrates the classic ground glass bony appearance in great detail and helps with the diagnosis of FD, while excluding other bony pathology. The patient’s corroborative MRI brain with and without contrast and MRI brain perfusion images are presented to further characterize this pathology along with its orbital and ocular complications. Given the significant mass-effect on the ocular structures, the patient underwent orbital surgery with removal of as much of the lesion as possible. On macroscopic pathology evaluation, the affected bone was rubbery and gritty when sectioned. Microscopically, remnant fragments of woven bone of various size and shapes were seen with lack of an osteoblast rim. The bony fragments had a characteristic curvilinear, trabecular, and/or branching pattern. Post-surgical imaging demonstrated improvement in the mass-effect on orbital structures and proptosis, along with residual bony lesion.

Taking a crack at the dome: histopathology of a pachycephalosaurid (Dinosauria: Ornithischia) frontoparietal dome

Recent studies have identified numerous pathologies in the cranial domes of pachycephalosaurid dinosaurs. These studies utilized CT images of domes to identify secondary woven bone and sclerosis associated with the pathologies. These features were critical for diagnosing post-traumatic osteomyelitis, which supported the head-butting behaviour hypothesis. However, conventional CT image resolution may not be sufficient to identify secondary woven bone or sclerotic bone in fossil specimens. UALVP 8504 (cf. Foraminacephale brevis), a dome possessing putative bone lesions, was thin-sectioned and micro-CT scanned. Thin sections revealed the lesions are lytic, without any secondary woven bone or sclerosis, falsifying the diagnosis of osteomyelitis. The morphology and histology of the lesions of UALVP 8504 are not diagnostic and resemble both post-traumatic and non-traumatic lesions. However, UALVP 8504 possesses shifted vascular canals (repositioning via remodeling, which maintains anatomical position throughout ontogeny) that are decoupled from growth (), and drifting osteons (secondary osteons where resorption occurs longitudinally and transversely). These demonstrate that the dome has sustained external mechanical loading, likely resulting from an impact or multiple impacts, consistent with the head-butting hypothesis. These impacts may have damaged overlying soft tissues and formed the lesions along the surface. Therefore, we suspect that the pathologies in UALVP 8504 are post-traumatic.

The Bone Cartilage Interface and Osteoarthritis

This review describes results obtained with tissue from prior studies of equine and human osteoarthritis (OA). The main methods considered are scanning electron microscopy, novel methods in light microscopy and X-ray Micro-tomography. The same samples have been re-utilised in several ways. The tissues described are hyaline articular cartilage (HAC; or substitutes), with its deep layer, articular calcified cartilage (ACC), whose deep surface is resorbed in cutting cone events to allow the deposition of subchondral bone (SCB). Multiple tidemarks are normal. Turnover at the osteochondral (ACC-HAC-SCB) junction is downregulated by overload exercise, conversely, during rest periods. Consequent lack of support predisposes to microfracture of the ACC-SCB plate, in the resorption-related repair phase of which the plate is further undermined to form sink holes. The following characteristics contribute to the OA scenario: penetrating resorption canals and local loss of ACC; cracking of ACC and SCB; sealing of cracks with High-Density Mineral Infill (HDMI); extrusion of HDMI into HAC to form High-Density Mineral Protrusions (HDMP) in HAC which may fragment and contribute to its destruction; SCB marrow space infilling and densification with (at first) woven bone; disruption, fibrillation and loss of HAC; eburnation; repair with abnormal tissues including fibrocartilage and woven bone; attachment of Sharpey fibres to SCB trabeculae and adipocyte-moulded extensions to trabeculae (excrescences).

A MICROSTRUCTURE-BASED MECHANISTIC MODEL FOR BONE SAWING: PART 2 - ACOUSTIC ENERGY RATE PREDICTIONS

Part-2 of this paper is focused on modeling the acoustic emission (AE) energy rate as a function of the specific cortical bone microstructures (viz., osteon, interstitial matrix, lamellar bone, and woven bone) and the depth-of-cut encountered by the bone sawtooth. First, the AE signal characteristics from the sawing experiments (in Part-1) are related to the pure haversian and pure plexiform regions of the cut. Using the cutting force predictions from Part-1 as input, the AE energy rate is then modeled in terms of the energies dissipated in the shearing and ploughing zones encountered by the rounded cutting edge. For this calculation, the rounded edge geometry of the sawtooth is modeled as a combination of (i) shear-based cutting from a negative rake cutting tool; and (ii) ploughing deformation from a round-nose indenter. The spread seen in the AE energy rate is captured by modeling the variations in sawed surface height profile, tool cutting edge geometry, and porosity of the bone. The model calibration and validation protocols are similar to those used in Part-1. The validated AE model is useful for process planning both in terms of its ability to predict AE energy rate trends and cutting force variations, based on the differences in the underlying bone microstructures.