De novo steroidogenesis in tumor cells drives bone metastasis and osteoclastogenesis.

Osteoclasts play a central role in cancer-cell-induced osteolysis, but the molecular mechanisms of osteoclast activation during bone metastasis formation are incompletely understood. By performing RNA sequencing on a mouse breast carcinoma cell line with higher bone-metastatic potential, here we identify the enzyme CYP11A1 strongly upregulated in osteotropic tumor cells. Genetic deletion of Cyp11a1 in tumor cells leads to a decreased number of bone metastases but does not alter primary tumor growth and lung metastasis formation in mice. The product of CYP11A1 activity, pregnenolone, increases the number and function of mouse and human osteoclasts in vitro but does not alter osteoclast-specific gene expression. Instead, tumor-derived pregnenolone strongly enhances the fusion of pre-osteoclasts via prolyl 4-hydroxylase subunit beta (P4HB), identified as a potential interaction partner of pregnenolone. Taken together, our results demonstrate that Cyp11a1-expressing tumor cells produce pregnenolone, which is capable of promoting bone metastasis formation and osteoclast development via P4HB.

Are Artificial Intelligence-Assisted Three-Dimensional Histological Reconstructions Reliable for the Assessment of Trabecular Microarchitecture?

Objectives: This study aimed to create a three-dimensional histological reconstruction through the AI-assisted classification of tissues and the alignment of serial sections. The secondary aim was to evaluate if the novel technique for histological reconstruction accurately replicated the trabecular microarchitecture of bone. This was performed by conducting micromorphometric measurements on the reconstruction and comparing the results obtained with those of microCT reconstructions. Methods: A bone biopsy sample was harvested upon re-entry following sinus floor augmentation. Following microCT scanning and histological processing, a modified version of the U-Net architecture was trained to categorize tissues on the sections. Detector-free local feature matching with transformers was used to create the histological reconstruction. The micromorphometric parameters were calculated using Bruker's CTAn software (version 1.18.8.0, Bruker, Kontich, Belgium) for both histological and microCT datasets. Results: Correlation coefficients calculated between the micromorphometric parameters measured on the microCT and histological reconstruction suggest a strong linear relationship between the two with p-values of 0.777, 0.717, 0.705, 0.666, and 0.687 for BV/TV, BS/TV, Tb.Pf Tb.Th, and Tb.Sp, respectively. Bland-Altman and mountain plots suggest good agreement between BV/TV measurements on the two reconstruction methods. Conclusions: This novel method for three-dimensional histological reconstruction provides researchers with a tool that enables the assessment of accurate trabecular microarchitecture and histological information simultaneously.

Management of Odontogenic Sinusitis: Results with Single-Step FESS and Dentoalveolar Surgery.

OBJECTIVE: Odontogenic sinusitis (OS) is a well-known and important border of specialties in otorhinolaryngology and dentoalveolar surgery. Odontogenic sinusitis can develop due to iatrogenic harm or odontogenic infection. The gold standard diagnostic method is clinical and radiological-CBCT (cone beam computed tomography)-examination. The treatment of this condition requires collaboration between ENT and dentoalveolar surgery specialists and can be non-surgical or surgical based on staging. This paper aims to share the results of our clinical study whereby complex therapy was administered by a dentoalveolar surgeon and an otorhinolaryngologist in cooperation. PATIENTS AND METHODS: We conducted a retrospective study comprising 111 OS patients who underwent complex therapy between 2016 and 2023 at Semmelweis University, Budapest, Hungary. All patients were treated with concurrent FESS (functional endoscopic sinus surgery) and dentoalveolar surgery. Follow-up was based on symptoms, clinical examination and CBCT imaging. RESULTS: Of the 111 patients, 107 were successfully treated with concurrent FESS and dentoalveolar surgery, and only 4 had further symptoms following the complex therapy and needed retreatment. CONCLUSIONS: The complex, single-session therapy involving FESS and oral surgery is an effective treatment method, which is less invasive and associated with fewer complications compared to previous interventions, such as the Luc-Caldwell procedure.

MRI compatibility of orthodontic brackets and wires: systematic review article.

BACKGROUND: Before the magnetic resonance imaging (MRI) examination fixed orthodontic devices, such as brackets and wires, cause challenges not only for the orthodontist but also for the radiologist. Essentially, the MRI-safe scan of the fixed orthodontic tools requires a proper guideline in clinical practice. Therefore, this systematic review aimed to examine all aspects of MRI-safe scan, including artifact, thermal, and debonding effects, to identify any existing gaps in knowledge in this regard and develop an evidence-based protocol. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was used in this study. The clinical question in "PIO" format was: "Does MRI examination influence the temperature of the orthodontic devices, the size of artifacts, and the debonding force in patients who have fixed orthodontic bracket and/or wire?" The search process was carried out in PubMed, PubMed Central, Scopus, and Google Scholar databases. The search resulted in 1310 articles. After selection according to the eligibility criteria, 18 studies were analyzed by two reviewers. The risk of bias was determined using the Quality In Prognosis Studies tool. RESULTS: Out of the eligible 18 studies, 10 articles examined the heating effect, 6 were about the debonding effect, and 11 measured the size of artifact regarding brackets and wires. Considering the quality assessment, the overall levels of evidence were high and medium. The published studies showed that heating and debonding effects during MRI exposure were not hazardous for patients. As some wires revealed higher temperature changes, it is suggested to remove the wire or insert a spacer between the appliances and the oral mucosa. Based on the material, ceramic and plastic brackets caused no relevant artifact and were MRI-safe. Stainless steel brackets and wires resulted in susceptibility artifacts in the orofacial region and could cause distortion in the frontal lobe, orbits, and pituitary gland. The retainer wires showed no relevant artifact. CONCLUSIONS: In conclusion, the thermal and debonding effects of the fixed orthodontic brackets and wires were irrelevant or resoluble; however, the size of the artifacts was clinically relevant and determined most significantly the feasibility of fixed brackets and wires in MRI examination.

Targeted histological evaluation shows high incidence of actinomyces infection in medication-related osteonecrosis of the jaws.

Medication-Related Osteonecrosis of the Jaws (MRONJ) is a difficult-to-treat complication of the therapy of osteoporosis and some malignancies cured with bisphosphonates and antiresorptive drugs. The pathomechanism is unclear, but there is increasing observation that Actinomyces infection may play a role in its development and progression. The aim of our study was to demonstrate that histological examination using a validated triple staining procedure for Actinomyces bacteria strains can detect a high rate of Actinomyces infection in patient's samples with MRONJ. 112 previously hematoxylin-eosin (HE) stained samples submitted with the clinical diagnosis of MRONJ were re-evaluated histologically using an appropriate triple special staining validated for the identification of Actinomyces infection. During the first evaluation, when pathologists did not specifically look for Actinomyces, only 8.93% of the samples were reported as positive. In contrast, re-evaluation with triple staining provided a yield of 93.7% positive samples, therefore, we suggest the triple special staining to be standard in MRONJ histology evaluation. These results show that if the clinician suspects Actinomyces infection and brings this to the attention of the pathologist, it could significantly increase the number of correct diagnoses. It serves as an aid for clinicians in therapeutic success of MRONJ by selecting a long-term adequate antibiotic medication which is suitable for the elimination of actinomyces infection.

Evaluation of the effect of vitamin D3 on mandibular condyles in an ovariectomized mouse model: a micro-CT study.

BACKGROUND: This study aimed to investigate the effect of ovariectomy and vitamin D3 on bone microstructure; this effect was examined in three regions of interest at one femoral and two mandibular sampling sites bone in an ovariectomized mouse model. METHODS: Thirty-six week-old female mice were randomly divided into three groups: 10 subjects were given oral cholecalciferol (vitamin D3) daily for 6 weeks after undergoing bilateral ovariectomy (D3 group), while 10 ovariectomized subjects (OVX) and 10 subjects who underwent a sham operation (SHAM) received peanut oil daily during the investigation. After extermination, the left hemimandible and femur were removed and scanned by micro-CT. The bone micromorphology parameters were analyzed and the BMD was calculated. RESULTS: The bone volume fraction (BV/TV) was significantly lower in the trabecular bone of the mandibular condyle in the OVX group than in the SHAM and D3 groups. Also there was a significant difference between the SHAM and D3 groups. The specific bone surface (BS/BV) was significantly higher in the OVX and D3 groups than in the SHAM group. Trabecular thickness (Tb.Th) was significantly higher in the SHAM group, and the trabecular bone pattern factor (Tb.Pf) was significantly higher in the OVX group than in the other two groups. Bone mineral density (BMD) of the femur and the mandible was significantly lower in the OVX group than in the SHAM and D3 groups. CONCLUSIONS: Our results show that ovariectomy causes a significantly weaker bone microstructure in the mandibular condyle, where the protective effect of vitamin D3 resulted in a partial resorption.

Evaluation of the Histomorphometric and Micromorphometric Performance of a Serum Albumin-Coated Bone Allograft Combined with A-PRF for Early and Conventional Healing Protocols after Maxillary Sinus Augmentation: A Randomized Clinical Trial.

The aim of this study was to compare the microarchitecture of augmented bone following maxillary sinus augmentation (MSA) after healing periods of 3 (test) and 6 (control) months using the combination of advanced platelet-rich fibrin (A-PRF) and a serum albumin-coated bone allograft (SACBA). Twenty-six patients with 30 surgical sites who required two-stage MSA were enrolled and grafted with the combination of A-PRF and SACBAs. The surgical sites were randomly allocated to the test or control group. During implant site preparation, 17 bone core biopsy samples were collected from each study group for histological, histomorphometric and micromorphometric analysis. Resonance frequency analysis was performed at the time of implant placement and 6, 8, 10, and 12 weeks postoperatively. The percentage of newly formed bone was 44.89 ± 9.49% in the test group and 39.75 ± 8.15% in the control group (p = 0.100). The results of the µCT analysis showed no significant differences in morphometric parameters between the study groups. The implant stability quotient was not significantly different between the two groups at 10 and 12 weeks postoperatively. Based on these findings, the total treatment time may be reduced by 3 months with the use of A-PRF and SACBAs for two-stage MSA.

Albumin-Impregnated Allograft Filling of Surgical Extraction Sockets Achieves Better Bone Remodeling Than Filling with Either Blood Clot or Bovine Xenograft.

PURPOSE: The goal of this study was to compare bone graft materials in mandibular third molar extraction sockets and to monitor bone remodeling and complications. MATERIALS AND METHODS: Patients with bilateral, impacted mandibular third molars were involved. Twenty-four patients were planned to be randomly assigned to three possible treatments: (1) the control sockets were left empty; (2) the socket was filled with bovine xenograft (Bio-Oss); or (3) the socket was filled with albumin-impregnated bone allograft (BoneAlbumin). Postoperative pain during the first week was determined with the visual analog scale. Cone beam computed tomography (CBCT) images were taken at 6 and 12 weeks and 1 year postoperatively for micromorphologic analysis and measurement of pocket depth at the second molar. Patients and image analyses were blinded toward the treatment group (randomized double-blind split-mouth design). RESULTS: Postoperative pain was lowest in the allograft group (control: 5.06 ± 0.53; xenograft: 5.85 ± 0.42; allograft: 3.94 ± 0.52; P < .05). At weeks 6 and 12, early signs of remodeling were observed in the allograft group and the controls, while bone xenograft was still demarcated from the host bone. The 1-year CBCT images showed complete remodeling and integration of allograft with natural trabecular structure, while the xenograft particles were still visible. Support for the second molar was significantly better, as evidenced by less deep and prevalent pockets in the allograft-filled group compared with the controls (P = .017). CONCLUSION: Filling an extraction socket with albumin-integrated allografts provides superior bone regeneration compared to either native bone buildup or xenograft application or socket regeneration without bone grafting.

Comparison between Micro-Computed Tomography and Cone-Beam Computed Tomography in the Assessment of Bone Quality and a Long-Term Volumetric Study of the Augmented Sinus Grafted with an Albumin Impregnated Allograft.

The purpose of our study was to compare micromorphometric data obtained by cone-beam computed-tomography (CBCT) and microcomputed-tomography (micro-CT) of the augmented sinus and to evaluate the long-term stability of the bone gain achieved using BoneAlbumin. Sinus lifts, and after 6-months, healing bone-biopsy and implant placement were carried out. Specimens were analyzed by micro-CT. A total of 16 samples were collected from nine patients (mean age 54.7 ± 6.5 years). Pre-, postoperative, and 3-year control CBCT-data were registered to determine from where the biopsy samples were harvested. Micromorphometric variables were calculated from the micro-CT- and CBCT-data, and their correlation was determined by Spearman's test. The volume of augmented bone was calculated at the time of implant placement and after 3 years. A positive correlation was found between bone-volume fraction, trabecular-separation, open-, and total-porosity, while a negative correlation was found between trabecular-thickness obtained from CBCT- and micro-CT-data (p < 0.05). Mean volumetric reduction of 39.28% (11.88-60.02%) was observed. Correlation of CBCT- and micro-CT-data suggested that micromorphometric analysis of CBCT reconstructions of the augmented sinuses provided reliable information on the microarchitecture of augmented bone. CBCT as a modality might be adequate in the analysis of bone quality in the augmented sinus. At the 3-year, control sinus grafts showed volumetric stability.

Cell physiological effects of glass ionomer cements on fibroblast cells.

The cytotoxicity of glass ionomer cements (GICs) was investigated using a novel, cost-effective, easy-to-perform and standardized test. GIC rings were made using in-house designed, custom-made moulds under sterile conditions; 10 with Fuji Equia and 10 with Fuji Triage capsules, placed in direct contact with primary human gingival fibroblasts (HGF) and immortalized human fibroblasts (HFF1). On day 1, 4, 14 and 21, an AlamarBlue® (resazurin) assay was completed towards determining the effects of the GICs on metabolic activities of the cells, whilst cell morphology was examined by light microscopy. The influence of the compounds released from the GIC rings on cell physiological effects (viability, proliferation and adhesion) during 24 h incubation was further investigated by impedimetry. Result trends obtained from this battery of techniques were complementary. At 100 v/v% concentration, the released compounds from Equia were strongly cytotoxic, while at lower concentration (0, 4, 20 v/v%) they were not cytotoxic. In contrast, Triage elicited only slightly transient cytotoxicity. The method proposed has been proved as being efficient, reliable and reproducible and may be useful in quick testing of the cytotoxicity of similar biomaterials by using an immortalized cell line.

Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming.

Dosage forms with increased gastric residence time are promising tools to increase bioavailability of drugs with narrow absorption window. Low-density floating formulations could avoid gastric emptying; therefore, sustained drug release can be achieved. Our aim was to develop a new technology to produce low-density floating formulations by melt foaming. Excipients were selected carefully, with the criteria of low gastric irritation, melting range below 70°C and well-known use in oral drug formulations. PEG 4000, Labrasol and stearic acid type 50 were used to create metronidazole dispersion which was foamed by air on atmospheric pressure using in-house developed apparatus at 53°C. Stearic acid was necessary to improve the foamability of the molten dispersion. Additionally, it reduced matrix erosion, thus prolonging drug dissolution and preserving hardness of the moulded foam. Labrasol as a liquid solubiliser can be used to increase drug release rate and drug solubility. Based on the SEM images, metronidazole in the molten foam remained in crystalline form. MicroCT scans with the electron microscopic images revealed that the foam has a closed-cell structure, where spherical voids have smooth inner wall, they are randomly dispersed, while adjacent voids often interconnected with each other. Drug release from all compositions followed Korsmeyer-Peppas kinetic model. Erosion of the matrix was the main mechanism of the release of metronidazole. Texture analysis confirmed that stearic acid plays a key role in preserving the integrity of the matrix during dissolution in acidic buffer. The technology creates low density and solid matrix system with micronsized air-filled voids.

Difficulties in the diagnosis of periapical translucencies and in the classification of cemento-osseous dysplasia.

BACKGROUND: Cemento-osseous dysplasia is a benign fibro-osseous lesion of the tooth-bearing region of the jaws with a periodontal ligament origin. It appears predominantly in Black and Asian middle-aged females. Its importance is that it could mimic a periapical lesion in the early, translucent stage. CASE PRESENTATION: In this report a rare case of familial cemento-osseous dysplasia is presented: a 50-years old Caucasian woman with labial paraesthesia and radiological translucency around the roots of the mandibular incisors and the first molar teeth. The lesion around the first molar was diagnosed as periapical granuloma and a root canal treatment was carried out. The diagnosis of florid cemento-osseous dysplasia and the treatment plan based on two- and three-dimensional radiographic examinations were certified histologically after surgical removal of the lesion. We screened the family members - including the patient's mother, daughter and son - and identified a periapical version of cemento-osseous dysplasia in the daughter. Our case highlights the difficulties of differential diagnosis of cemento-osseous dysplasia and other periapical pathologies. The inconsistencies in the present classification of cemento-osseous dysplasia are also discussed with a proposal for a different classification based on new aspects that would be very helpful in setting up a correct treatment plan. CONCLUSION: Differentiation of endodontic and non-endodontic origin of radiolucency and distinguishing it from anatomical landmarks by appropriate clinical evaluation and using vitality testing can give an opportunity to prevent unnecessary endodontic treatment. The current categories of cemento-osseous dysplasia classification do not cover the early stage of a hereditary florid form of cemento-osseous dysplasia. Instead of anatomical location of the lesion, clinical and genetic features may be recommended as parameters of cemento-osseous dysplasia classification.

Effectiveness of Parameters in Quantifying Root Canal Morphology Change after Instrumentation with the Aid of a Microcomputed Tomography.

The objective of this study was to analyse the effectiveness of some parameters which characterise the change in morphology in human root canals subjected to ProTaper rotary enlargement with the help of an X-ray microfocus computed tomography (MCT) and to introduce a novel parameter that is effective in quantifying changes in root canal morphology. Ten each straight and curved root canals with mature apices chosen from extracted human upper incisor and canine teeth were scanned with MCT before and after canal shaping using ProTaper rotary instruments in order to facilitate three-dimensional digital reconstruction and quantitative gauging of relevant instrumental parameters and changes therein (surface area and volume). Root canal geometry change and the effectiveness of shaping were quantified with Structure Model Index change (ΔSMI) and surface area change to volume change ratio (ΔSA/ΔV). These two parameters were also tested on simulated canals. Postinstrumentation cross-sectional changes were also analysed, but only on the plastic blocks. Statistical analysis of parameters was carried out to verify the significance of results. Analysis of cross-sectional shape of postinstrumented resin simulated canals showed statistically significant decrease in Form Factor (p<0.05) and statistically significant increase in Eccentricity (p<0.005). ΔSMI did not show significant difference between straight and curved canals. SMI values showed bidirectional change during root enlargement which questions the reliability of this metric in analysing instrumentation. Statistically significant (p<0.005) deviations in ΔSA/ΔV were quantified as 1.92 and 3.22 for straight and curved human canals, respectively. Instrumentation-induced canal geometry change was determined to be more pronounced in curved canals using the novel parameter ΔSA/ΔV. This has been proven as being a statistically accurate and reproducible parameter for quantitative characterisation of root canal geometry change and differentiation of preparational efficacy for both straight and curved root canals.

Hematopoietic or Osteoclast-Specific Deletion of Syk Leads to Increased Bone Mass in Experimental Mice.

Syk is a non-receptor tyrosine kinase critically involved in signaling by various immunoreceptors including B-cell-receptors and activating Fc-receptors. We have previously shown that Syk also mediates immunoreceptor-like signals required for the in vitro development and function of osteoclasts. However, the perinatal lethality of Syk-/- mice precluded the analysis of the role of Syk in in vivo bone metabolism. To overcome that problem, we generated mice with osteoclast-specific (SykΔOC ) or hematopoietic (SykΔHaemo ) Syk deficiency by conditional deletion of Syk using Cre recombinase expressed under the control of the Ctsk or Vav1 promoter, respectively. Micro-CT analysis revealed increased bone trabecular density in both SykΔOC and SykΔHaemo mice, although hematopoietic Syk deficiency caused a more severe phenotype than osteoclast-specific Syk deficiency. Osteoclast-specific Syk deficiency reduced, whereas hematopoietic Syk deficiency completely blocked in vitro development of osteoclasts. Both interventions inhibited the resorptive activity of osteoclasts and osteoclast-specific gene expression. Kinetic analysis of Syk protein levels, Cre expression and the genomic deletion of the Sykflox allele revealed complete and early deletion of Syk from SykΔHaemo osteoclasts whereas Syk was incompletely deleted at a later stage of osteoclast development from SykΔOC cultures. Those results provide an explanation for the in vivo and in vitro difference between the SykΔOC and SykΔHaemo mutant strains and suggest late activation of, and incomplete target gene deletion upon, osteoclast-specific Cre expression driven by the Ctsk promoter. Taken together, our results indicate that Syk plays an indispensable role in osteoclast-mediated in vivo bone resorption and suggest that Syk-specific inhibitors may provide therapeutic benefit in inflammatory and other diseases characterized by excessive osteoclast-mediated bone resorption.

Significance of the Tks4 scaffold protein in bone tissue homeostasis.

The main driver of osteoporosis is an imbalance between bone resorption and formation. The pathogenesis of osteoporosis has also been connected to genetic alterations in key osteogenic factors and dysfunction of bone marrow mesenchymal stem/stromal cells (BM-MSCs). Tks4 (encoded by the Sh3pxd2b gene) is a scaffold protein involved in podosome organization. Homozygous mutational inactivation of Sh3pxd2b causes Frank-ter Haar syndrome (FTHS), a genetic disease that affects bone tissue as well as eye, ear, and heart functions. To date, the role of Tks4 in adult bone homeostasis has not been investigated. Therefore, the aim of this study was to analyze the facial and femoral bone phenotypes of Sh3pxd2b knock-out (KO) mice using micro-CT methods. In addition to the analysis of the Sh3pxd2b-KO mice, the bone microstructure of an FTHS patient was also examined. Macro-examination of skulls from Tks4-deficient mice revealed craniofacial malformations that were very similar to symptoms of the FTHS patient. The femurs of the Sh3pxd2b-KO mice had alterations in the trabecular system and showed signs of osteoporosis, and, similarly, the FTHS patient also showed increased trabecular separation/porosity. The expression levels of the Runx2 and osteocalcin bone formation markers were reduced in the bone and bone marrow of the Sh3pxd2b-KO femurs, respectively. Our recent study demonstrated that Sh3pxd2b-KO BM-MSCs have a reduced ability to differentiate into osteoblast lineage cells; therefore, we concluded that the Tks4 scaffold protein is important for osteoblast formation, and that it likely plays a role in bone cell homeostasis.

Serum albumin-coated bone allograft (BoneAlbumin) results in faster bone formation and mechanically stronger bone in aging rats.

Serum albumin-coated bone allografts (BoneAlbumin) have successfully supported bone regeneration in various experimental models by activating endogenous progenitors. However, the effect of tissue aging, linked to declining stem cell function, has yet to be explicitly examined within the context of BoneAlbumin's regenerative capacity. Stem cell function was tested with an in vitro attachment assay, which showed that albumin coating increases stem cell attachment on demineralized bone surfaces in an aging cell population. Bone regeneration was investigated in vivo by creating critical size bone defects on the parietal bones of aging female rats. Demineralized bone matrices with and without serum albumin coating were used to fill the defects. Bone regeneration was determined by measuring the density and the size of the remaining bone defect with computed tomography (CT). Microcomputed tomography (MicroCT) and mechanical testing were performed on the parietal bone explants. In vivo CT and ex vivo microCT measurements showed better regeneration with albumin-coated grafts. Additionally, the albumin-coated group showed a twofold increase in peak fracture force compared with uncoated allografts. In the present study, serum albumin-coated demineralized bone matrices successfully supported faster and functionally superior bone regeneration in aging rats. Because stem cell function, a key contributor of bone remodelling, decreases with age and serum albumin is an effective activator of endogenous progenitor cells, this method could be an effective and safe adjuvant in bone regeneration of aging adult and osteo-compromised populations.

Development of a quantitative preclinical screening model for implant osseointegration in rat tail vertebra.

OBJECTIVES: Functional tooth replacement and bone regeneration are parts of the daily practice in modern dentistry, but well-reproducible and relatively inexpensive experimental models are still missing. We aimed to develop a new small animal model to monitor osseointegration utilizing the combination of multiple evaluation protocols. MATERIAL AND METHODS: After cutting the tail between the C4 and C5 vertebrae in Wistar rats, costume made, parallel walled, non-threaded implants were placed into the center of the tail parallel with its longitudinal axis using a surgical guide. Osseointegration of the titanium implants was followed between 4 and 16 weeks after surgery applying axial extraction force, and resonance frequency analysis as functional tests, and histomorphometry and micro-CT as structural evaluations. RESULTS: In functional tests, we observed that both methods are suitable for the detection of the time-dependent increase in osseointegration, but the sensitivity of the pull-out technique (an approximately five times increase with rather low standard error) was much higher than that of the resonance frequency analysis. In structural evaluations, changes in the detected bone implant contact values measured by histomorphometry (yielding 1.5 times increase, with low variations of data) were more reliable than micro-CT based evaluations to screen the developments of contact between bone and implant. CONCLUSION: Our results provide evidence that the caudal vertebrae osseointegration model is useful for the preclinical evaluation of implant integration into the bone. CLINICAL RELEVANCE: The combination of the biomechanical and structural tests offers a well-reproducible small animal system that can be suitable for studying the integration of various implant materials and surface treatments.

Comparison of hand and semiautomatic tracing methods for creating maxillofacial artificial organs using sequences of computed tomography (CT) and cone beam computed tomography (CBCT) images.

INTRODUCTION: The aim of this study was to compare the paranasal sinus volumes obtained by manual and semiautomatic imaging software programs using both CT and CBCT imaging. METHODS: 121 computed tomography (CT) and 119 cone beam computed tomography (CBCT) examinations were selected from the databases of the authors' institutes. The Digital Imaging and Communications in Medicine (DICOM) images were imported into 3-dimensonal imaging software, in which hand mode and semiautomatic tracing methods were used to measure the volumes of both maxillary sinuses and the sphenoid sinus. The determined volumetric means were compared to previously published averages. RESULTS: Isometric CBCT-based volume determination results were closer to the real volume conditions, whereas the non-isometric CT-based volume measurements defined coherently lower volumes. By comparing the 2 volume measurement modes, the values gained from hand mode were closer to the literature data. Furthermore, CBCT-based image measurement results corresponded to the known averages. CONCLUSIONS: Our results suggest that CBCT images provide reliable volumetric information that can be depended on for artificial organ construction, and which may aid the guidance of the operator prior to or during the intervention.

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells.

Remineralization of demineralized bone matrix in critical size cranial defects in rats: A 6-month follow-up study.

The key drawback of using demineralized bone matrix (DBM) is its low initial mechanical stability due to the severe depletion of mineral content. In the present study, we investigated the long-term regeneration of DBM in a critical size bone defect model and investigated the remineralization after 6 months. Bone defects were created in the cranium of male Wistar rats which were filled with DBM or left empty as negative control. In vivo bone formation was monitored with computed tomography after 11, 19, and 26 weeks postoperatively. After 6 months, parietal bones were subjected to micro-CT. Mineral content was determined with spectrophotometric analysis. After 11 weeks the DBM-filled bone defects were completely closed, while empty defects were still open. Density of the DBM-treated group increased significantly while the controls remained unchanged. Quantitative analysis by micro-CT confirmed the in vivo results, bone volume/tissue volume was significantly lower in the controls than in the DBM group. The demineralization procedure depleted the key minerals of the bone to a very low level. Six months after implantation Ca, P, Na, Mg, Zn, and Cr contents were completely restored to the normal level, while K, Sr, and Mn were only partially restored. The remineralization process of DBM is largely complete by the 6th month after implantation in terms of bone density, structure, and key mineral levels. Although DBM does not provide sufficient sources for any of these minerals, it induces a faster and more complete regeneration process. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1336-1342, 2016.