Bone regeneration by freeze-dried composite of octacalcium phosphate collagen and teriparatide.

OBJECTIVE: Octacalcium phosphate (OCP) and collagen (col) composite (OCPcol) demonstrated superior bone regeneration properties, and its commercialization appears to be forthcoming. As a practical medical material for new combination products, we developed a freeze-dried composite with OCPcol and teriparatide (TPTD) (OCPcolTPTDf), and investigated its bone regenerative properties. MATERIALS AND METHODS: A disk of OCPcol was made by mixing OCP granules and atelocollagen for medical use. Then, OCPcolTPTDf was prepared by impregnation of the OCPcol disk with 1.0 or 0.1 µg of TPTD solution (OCPcolTPTDf 1.0 and OCPcolTPTDf 0.1, respectively) followed by lyophilization. In vitro release profiles of TPTD from OCPcolTPTDf were determined using an enzyme-linked immunosorbent assay. Implantation of OCPcolTPTDf or OCPcol was carried out for a rat critical-sized calvarial defect. And five defects in each group were collected after 12 weeks of implantation. RESULTS: The retention-release profiles of TPTD from OCPcolTPTDf supported a higher degree of retention of TPTD. Radiographic, histological, and histomorphometric examinations indicated that regenerated bone was filled in most of the defects of the OCPcolTPTDf. Additionally, the OCPcolTPTDf groups showed significantly enhanced bone regeneration compared with the OCPcol group. CONCLUSIONS: These results suggested that this newly developed bone regenerative composite could be a practical medical material.

[A Perspective on Innovation for Efficient Medical Practice in View of Undergraduate and Postgraduate Education and Training in Laboratory Medicine].

Continuous advances in medical laboratory technology have driven major changes in the practice of laboratory medicine over the past two decades. The importance of the overall quality of a medical laboratory has been ever-increasing in order to improve and ensure the quality and safety of clinical practice by physicians in any type of medical facility. Laboratory physicians and professional staff should challenge themselves more than ever in various ways to cooperate and contribute with practicing physicians for the appropriate utilization of laboratory testing. This will certainly lead to a decrease in inappropriate or unnecessary laboratory testing, resulting in reducing medical costs. In addition, not only postgraduate, but also undergraduate medical education/training systems must be markedly innovated, considering recent rapid progress in electronic information and communication technologies.

The regenerated bone quality by implantation of octacalcium phosphate collagen composites in a canine alveolar cleft model.

OBJECTIVE: Synthetic octacalcium phosphate and porcine atelocollagen composites significantly enhanced bone regeneration more than ß-tricalcium phosphate collagen composite and hydroxyapatite collagen composite in a rat cranial defect model. However, the long-term stability and quality of octacalcium phosphate collagen (OCP/Col) composites-derived regenerated bone, when implanted in a canine alveolar cleft model, have yet to be elucidated. The present study investigated the longterm stability and quality of bone regenerated by OCP/Col. DESIGN: Disks of OCP/Col or collagen were implanted in a canine alveolar-cleft model (n = 6). Then, bone regeneration in the implanted areas was investigated macroscopically, radiographically, and histologically at 10 months after implantation. In addition, three-dimensional quantitative images of regenerated bone were analyzed by microcomputed tomography. RESULTS: Macroscopically, the OCP/Col treated alveolus was clearly augmented, and radio-opacity in the OCP/Col implanted area was comparable to that of the original alveolus bone. On histological analysis, the area was mostly filled with newly formed bone, and a few granules of implanted OCP/Col were enclosed in it. In the microcomputed tomography analysis, the regenerated bone volume in the OCP/Col group was larger than that in the collagen group. OCP/Col-derived bone consisted of outer cortical and inner cancellous structure with dense trabeculae and seemed like the original bone structure. CONCLUSIONS: OCP/Co composites could be a useful bone regenerative material to substitute for autogenous bone because their implantation could elicit high bone regeneration and active structural reconstitution.

[Significance of clinical laboratory accreditation based on ISO 15189, and recent trend of international clinical laboratory accreditation program].

ISO 15189 was first published in 2003, its second edition in 2007, and its third edition in 2012 by the ISO. Since 2003, through the approval of ILAC, ISO 15189 has been used for the accreditation of clinical/medical laboratories throughout the world, and approximately 5,000 clinical laboratories have now been accredited. In Japan, the JAB, in cooperation with the JCCLS, introduced the clinical laboratory accreditation program based on ISO 15189 in 2005, and 70 labs had been accredited by January 2014. It has been purely voluntary, without any governmental or regulatory involvement so far. However, it has been gradually accepted to be significant for maintaining quality management and for the improvement of clinical laboratory efficiency. The program will expand widely throughout the world in order to accomplish "one-stop testing" among clinical laboratories, at least regarding frequently-used routine laboratory tests.

Histological evaluation of tissue destruction in mouse tongues caused by cryosurgery.

Introduction: Cryosurgery is recognized as a treatment option for various types of oral lesions. Although cryosurgery is less invasive and easier to perform than surgical treatments, adverse events, such as stomatitis and scarring can occur if the freezing is excessive. There are few studies regarding the effects of cryosurgery on the surrounding soft tissues. Thus, this study investigated the extent of tissue destruction and healing progress in tongues of mice who underwent cryosurgery. Methods: Eight-week-old male BALB/c mice were used. An instrument cooled with liquid nitrogen was lightly touched on the right side of the tongue for 5 s, and a second test was performed 10 s later. Histological evaluation was performed 3, 7, and 14 days after cryosurgery. Blood vessels were evaluated with India ink at 1, 3, 7, 14, and 21 days after cryosurgery. Results: Destruction of the soft tissue spread to the left side of the tongue after 3 days. At 7 days, it was confirmed that the muscle tissue was in the process of repair and was completely repaired at 14 days. Although blood vessels were not confirmed at 3 days, they were visible after seven days and were confirmed at 21 days all over the tongue. Discussion and Conclusion: These results indicated that the tissue destruction caused by cryosurgery was extensive and suggest that the duration and frequency of freezing should be minimized for clinical use. Lay Summary: Cryosurgery is a treatment method for various types of oral lesions. Freezing the lesion causes the tissue to collapse, resulting in its disappearance. Although cryosurgery is less invasive and easier to perform than surgical treatments, adverse events, such as stomatitis and scarring can occur if the freezing is excessive. This study investigated the extent of tissue destruction and healing progress in tongues of mice who underwent cryosurgery.The right side of mice tongues were frozen by an instrument cooled with liquid nitrogen for 5 s, and a second test was performed 10 s later. The tissue destruction was evaluated at 3, 7, and 14 days after freezing. Blood vessels were evaluated with India ink at 1, 3, 7, 14, and 21 days after freezing. Tissue destruction spread to the left side of the tongue after 3 days. At 7 days, it was confirmed that the muscle tissue was in the process of repair and was completely repaired at 14 days. Blood vessel repair was confirmed at 21 days in the throughout tongue. These results indicated that the tissue destruction caused by cryosurgery was large and suggest that the duration and frequency of freezing should be minimized for clinical use.

Biocompatibility Evaluation of an Artificial Metallic Bone with Lattice Structure for Reconstruction of Bone Defect.

Mandibular reconstruction for large bone defects is performed with consideration of patients' specific morphology and sufficient strength. Metal additive manufacturing techniques have been used to develop biomaterials for mandibular reconstruction. Titanium artificial mandibles with a lattice structure have been proposed, and the optimal conditions for their strength to withstand mechanical stress around the mandible have been reported. This study investigated the biocompatibility of a titanium artificial bone with a lattice structure fabricated under optimal conditions. The samples were fabricated using metal additive manufacturing. Body diagonals with nodes (BDN) were selected as suitable lattice structures. Dode medium (DM) was selected for comparison. The samples were implanted into rabbit tibial defects and resected with the surrounding bone at two and four weeks. Specimens were evaluated radiographically, histologically, and histomorphometrically. Radiopacity in each lattice structure was observed at two and four weeks. Histological evaluation showed trabecular bone-like tissue inside the BDN compared to the DM at four weeks. No significant differences were noted in the bone volume inside the structures. This study demonstrated the in vivo compatibility of artificial metallic bones with a BDN structure under mechanical stress conditions.

Investigation of the Mechanical Strength of Artificial Metallic Mandibles with Lattice Structure for Mandibular Reconstruction.

Mandibular reconstructive surgery is necessary for large bone defects. Although various reconstruction methods have been performed clinically, there is no mandibular reconstruction method that meets both sufficient strength criteria and the patient's specific morphology. In this study, the material strength of the cylindrical lattice structures formed by electron-beam melting additive manufacturing using titanium alloy powder was investigated for mandibular reconstruction. The virtual strengths of 28 lattice structures were compared using numerical material tests with finite element method software. Subsequently, to compare the material properties of the selected structures from the preliminary tests, compression test, static bending test and fatigue test were conducted. The results showed that there were correlations with relative density and significant differences among the various structures when comparing internal stress with deformation, although there was a possibility of localized stress concentration and non-uniform stress distribution based on the lattice structure characteristics. These results suggest that the lattice structure of body diagonals with nodes and a cell size of 3.0 mm is a potential candidate for metallic artificial mandibles in mandibular reconstruction surgery.

Risk factors of medication-related osteonecrosis of the jaw: A clinical investigation.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable condition caused by drugs such as bisphosphonates and denosumab. This study investigated the changes in the incidence of MRONJ in the previous 10 years and examined the poor prognostic factors during surgery in at-risk patients. We compared 57 and 64 patients diagnosed with MRONJ at our hospital between January 2012 and December 2016 and January 2017 and December 2021, respectively. The disease stage and triggers at the time of initial diagnosis in eligible patients were investigated. Additionally, the adverse prognostic factors were examined in 166 patients at risk of MRONJ who underwent tooth extraction at our department during these 10 years. The results indicated that there was no change in the proportion of patients with osteoporosis and malignancy among those with MRONJ. The number of cases after tooth extraction decreased, and those after dental infections increased on comparing the recent 5 years and the preceding 5 years. The number of MRONJ patients receiving denosumab also increased. Denosumab was a significant post-extraction prognostic factor for delayed healing in the 166 patients at risk of MRONJ. The findings suggest that patients receiving denosumab should be closely monitored when undergoing surgery to prevent MRONJ.

Living on the edge: Crayfish as drivers to anoxification of their own shelter microenvironment.

Burrowing is a common trait among crayfish thought to help species deal with adverse environmental challenges. However, little is known about the microhabitat ecology of crayfish taxa in relation to their burrows. To fill this knowledge gap, we assessed the availability of oxygen inside the crayfish shelter by series of in-vivo and in-silico modelling experiments. Under modeled condition, we found that, except for the entrance region of the 200 mm, a flooded burrow microenvironment became anoxic within 8 h, on average. Multiple 12-hour day-night cycles, with burrows occupied by crayfish for 12 h and empty for 12 h, were not sufficient for refreshing the burrow microenvironment. We then examined the degree to which crayfish species with different propensities for burrowing are tolerant of self-created anoxia. From these experiments, primary and secondary burrowers showed best and most consistent tolerance-exhibiting ≥ 64% survival to anoxia and 25-91% survival of ≥ 9 h at anoxia, respectively. Tertiary burrowers exhibited little to no tolerance of anoxia with 0-50% survival to anoxia and only one species exhibiting survival (2%) of ≥ 9 h at anoxia. Results suggest that moderate to strongly burrowing crayfish can quickly draw down the dissolved oxygen in burrow water but appear to have conserved a legacy of strong tolerance of anoxia from their monophyletic ancestors-the lobsters-whereas tertiary burrowers have lost (or never evolved) this ability.

Condyle Fracture Fixed with Custom-Made Titanium Mesh and a Miniplate: A Case Report.

BACKGROUND Open reduction and internal fixation of condyle fractures are sometimes difficult for the upper region. This report presents a case of condyle fracture at the upper neck region treated with a custom-made titanium mesh and a titanium miniplate, which makes it easy to reposition the fragment and keep it in place. CASE REPORT A 20-year-old man was injured during a soccer match and was referred to our hospital with the symptom of trismus and deviation of the mandible to the left with an opened mouth. Fracture of the right condyle neck region was diagnosed; open reduction and internal fixation was planned under general anesthesia. A custom-made titanium mesh was prepared to make it easy to reposition the fragment and keep it in place because the reduction and fixation were expected to be difficult. The fracture region was exposed using the modified Risdon-Strasbourg approach. The segments were gripped with custom-made titanium mesh, and the condyle head was reduced easily. The segments were fixed with titanium mesh, a miniplate, and screws. Nine months after the operation, the mouth opening was good at 40 mm, there was no deviation of the mandible, and there was no breakage on the titanium mesh or plate. CONCLUSIONS This report presents a case of condyle fracture at the upper neck region reduced and fixed with a custom-made titanium mesh and a titanium miniplate, which make it easy to reposition the fragment and keep it in place.

A case of canalicular adenoma with anemia.

An 81-year-old woman presented with bleeding from a soft elastic bulge on the right buccal mucosa. Her medical history included hypertension, chronic renal failure, hysterectomy and a goiter operation. Certain investigations, such as blood tests, which confirmed the minimum hemoglobin level of 5.3 g/dl, computed tomography and magnetic resonance imaging (MRI), were conducted. MRI revealed features confirming the presence of a tumor involving the right buccal mucosa with high signal in T2-enhanced image. Considering the provisional diagnosis and image findings, the tumor mass was excised and histopathological examination of the biopsy specimen confirmed the diagnosis of a canalicular adenoma. Under the diagnosis of various clinical departments, the anemic state of the patient might be chiefly attributed to the bleeding from the tumor. Herein, we report a rare case of a canalicular adenoma in the right buccal mucosa with anemia due to bleeding from the tumor.

Teriparatide with Octacalcium Phosphate Collagen Composite Stimulates Osteogenic Factors.

Octacalcium phosphate and collagen composite (OCPcol) promotes osteogenic differentiation and angiogenesis, thereby enhancing bone regeneration. Although a newly developed freeze-dried composite of OCPcol and teriparatide (OCPcolTPTD) reinforced bone regeneration more than OCPcol, the mechanism of bone regeneration remains unresolved. In this study, disks containing OCPcolTPTD, OCPcol, or ß-tricalcium phosphate (ß-TCP) col were inserted into rodents with calvarial bone defects, before euthanasia 4 weeks later. Immunohistochemical and histochemical analyses were performed on bone samples to evaluate bone matrix development, angiogenesis, and osteoclast and osteoblast localization. In the OCPcolTPTD and OCPcol groups, bone regeneration was observed at the surface of calvarial dura mater and around acidophilic granular cells with abundant collagenous fiber-containing cells. Furthermore, the newly formed bone in the OCPcolTPTD group showed a larger total area and individual separated area than the other groups. Various osteogenic proteins were detected in the regenerated bone and peri-bone tissues by histochemistry and immunohistochemistry. Although the expression of several osteogenic biomarkers in the OCPcolTPTD group after 4 weeks of implantation was significantly lower than that in the OCPcol group, new bone formation by OCPcolTPTD in the center of the defect, where bone regeneration is difficult, tended to be superior to that by OCPcol. These results suggest that OCPcolTPTD enhanced bone regeneration more evenly and homogenously than OCPcol. Impact statement Our study suggests that octacalcium phosphate and collagen (OCPcol) together with a TPTD enhances bone regeneration in rodents with calvarial bone defects. Furthermore, we believe that composite of OCPcol and teriparatide (OCPcolTPTD) could be developed into novel clinical technique for the regeneration or repair of bone.

Tophaceous pseudogout of the temporomandibular joint extending into the cranium: a case report with literature review.

Pseudogout is a disease characterized by calcium pyrophosphate crystal deposition. Involvement of the temporomandibular joint (TMJ) is rare. We herein report a case of tophaceous pseudogout of the TMJ with cranial extension. An 83-year-old woman was referred to our institution for treatment of right TMJ pain. The patient's medical and family histories were unremarkable. Magnetic resonance imaging showed a mass of about 35 mm in diameter compressing the bottom of the right temporal lobe of the brain. Based on a clinical diagnosis of a right TMJ tumour, biopsy was performed under general anaesthesia. The histopathological diagnosis was pseudogout. Considering the risk of surgically induced brain damage, the patient's advanced age and her relatively good quality of life, the treatment plan simply involved the observation of the lesion. Fourteen months after biopsy, the patient's activities of daily living remained unchanged and she had no TMJ pain.

Intramuscular Myxoma of the Intrinsic Muscles of the Tongue: A Case Report with Literature Review.

Myxoma is a benign tumor of mesenchymal origin. It frequently occurs in the muscles of the hip and extremities; however, it rarely occurs in the head and neck region. This report describes the second case of an intramuscular myxoma of the tongue. A 23-year-old woman was referred to our institution for the diagnosis and treatment of a left tongue lesion. T2-weighted magnetic resonance imaging revealed an 8 × 6-mm mass in the tongue. Based on a clinical diagnosis of a tongue tumor, excisional biopsy was performed under general anesthesia. The histopathological diagnosis was an intramuscular myxoma. The postoperative course was uneventful, and there was no evidence of tumor recurrence 3 years after surgery.

A case of solitary neurofibroma in the maxillary gingiva.

Neurofibromas are benign tumors. They are known to be a manifestation of von Recklinghausen's disease (neurofibromatosis type 1) and tend to be generalized and rarely solitary. In this report, we present a case of solitary neurofibroma in the maxillary gingiva. A 39-year-old woman presented with a chief complaint of swollen gingiva. There were no special findings in her medical or family history. After a biopsy was performed under local anesthesia and a diagnosis of neurofibroma was made, tumor resection was performed under general anesthesia. The patient's progress was good, with no recurrence.

Osteosarcoma of the Mandible in an Elderly Patient.

Osteosarcoma is a malignant tumor in which the cancerous cells produce an osteoid matrix or mineralized bone. Jaw bones are affected in 6% of all osteosarcomas and are the fourth most common site of origin. Surgical treatment of osteosarcoma in elderly patients is rarely reported. Here, we report successful treatment of osteosarcoma arising in the mandible of a 90-year-old man. The patient was referred to our institution for diagnosis and treatment of an oral lesion. Intraoral examination revealed that a hard mass measuring 35 × 27 mm was located on the floor of the oral cavity, attached to the bone, and its growth displaced the tongue posteriorly. Therefore, he experienced difficulty in speech and swallowing. Biopsy of the mandibular mass was suspicious for chondrosarcoma. Preoperative examination did not detect critical risks for general anesthesia or surgery. Based on a clinical diagnosis of a malignant bone tumor of the mandible, segmental mandibular resection with reconstruction using a titanium plate was performed. Surgical site infection occurred on postoperative day 12, which was resolved by drainage, local irrigation, and administration of antibiotics. There was no delirium or cardiovascular or pulmonary complications. Surgery resolved the patient's difficulties in speech and swallowing. There was no evidence of tumor recurrence or metastasis 4 years after surgery. This case showed that it was not necessary to exclude surgical treatment merely because the patient was 90 years old. Indications for surgery should be determined individually to improve the patient's quality of life.

Hypoproteinemia Associated with a Gigantic Odontogenic Tumor: A Report of 2 Cases.

BACKGROUND Hypoproteinemia is caused by a decrease in protein level in the blood. This report describes 2 cases of hypoproteinemia associated with a gigantic odontogenic tumor. CASE REPORT Case 1, a 65-year-old man, visited our hospital with the chief concern of swelling in the right mandible, approximately 100 mm in diameter, and ameloblastoma was diagnosed. Abscess drainage was observed in the fistula of the tumors. Total protein and albumin levels were low before surgery. Hemimandibulectomy was performed under general anesthesia. The final pathological diagnosis based on the specimen was ameloblastic carcinoma. After surgery, the total protein and albumin levels improved and remained stable 6 months after the operation. At 21 months after surgery, there were no signs of recurrence. Case 2, a 60-year-old woman, visited our hospital with a chief concern of swelling in the left mandible, approximately 100 mm in diameter, and ameloblastoma was diagnosed. Abscess drainage was observed in the fistula of the tumors. The patient had a history of hypoproteinemia; preoperative levels of total protein and albumin were low, and edema of the body was observed before surgery. Hemimandibulectomy was performed under general anesthesia. The final pathological diagnosis based on the specimen was ameloblastoma. After surgery, the total protein and albumin levels improved, and remained stable 6 weeks after surgery. There were no signs of recurrence 9 months after surgery. CONCLUSIONS These 2 cases indicate the possibility that hypoproteinemia can be caused by plasma leakage from fistulas associated with gigantic odontogenic tumors.

The effect of synthetic octacalcium phosphate in a collagen scaffold on the osteogenicity of mesenchymal stem cells.

Although the efficacy of the in vivo osteogenic capabilities of synthetic octacalcium phosphate (OCP) crystal implantation can be explained through its stimulatory capacity for the differentiation of the host osteoblastic cell lineage, direct evidence that OCP supports bone regeneration by osteogenic cells in vivo has not been shown. Mesenchymal stem cells (MSCs) isolated from 4-week-old male Wistar rat long bones were pre-incubated in osteogenic or maintenance medium in the presence or absence of basic fibroblast growth factor (bFGF). OCP/Collagen (OCP/Col) or collagen disks were seeded with MSCs that had been pre-incubated in osteogenic medium containing bFGF, which exhibited the highest differentiation induction, and then incubated for an additional day. The disks were implanted in critical-sized calvaria defects of 12-week-old male Wistar rats and the specimens were analysed radiographically, histologically, histomorphometrically, and by micro-computed tomography (CT) imaging at 4 and 8 weeks after the implantation. The OCP/Col·MSCs group rapidly induced more bone regeneration, even within 4 weeks, compared to the OCP/Col group without MSCs. The bone mineral density of the OCP/Col·MSCs group was also greater than the OCP/Col group. The Col·MSCs group did not exhibit prominent osteogenicity. These results indicate that OCP crystals in a collagen matrix efficiently promote exogenously introduced osteogenic cells to initiate bone regeneration if the cells are pre-treated in a suitable differentiation condition.

Rhabdomyosarcoma in the maxillary gingiva of a child patient.

Rhabdomyosarcoma (RMS) is a rare, rapidly growing and aggressive malignant neoplasm mainly affecting children. However, mean age at the diagnosis of patients with gingival RMS is 26.9 years. A 12-year-old girl presented to our clinic with a chief complaint of trismus. The examination findings indicated a malignant tumor in the left maxillary gingiva. We performed a biopsy of the tumor, and the histopathological diagnosis was RMS. We report a rare case of primary RMS of the maxillary gingiva in a child patient.

Custom-Made Titanium Mesh Tray for Mandibular Reconstruction Using an Electron Beam Melting System.

Mandibular reconstruction using a titanium mesh tray and autologous bone is a common procedure in oral and maxillofacial surgery. However, there can be material problems-such as broken titanium mesh trays-which may undermine long-term functionality. This study was designed to investigate the optimal conditions for a titanium mesh tray with an ideal mandibular shape and sufficient strength, using computer-aided design, computer-aided manufacturing technology, and electron beam additive manufacturing. Specimens were prepared using Ti-6Al-4V extra low interstitial titanium alloy powder and an electron beam melting (EBM) system. The mechanical strength of the plate-shaped specimens was examined for differences in the stretch direction with respect to the stacking direction and the presence or absence of surface treatment. While evaluating the mechanical strength of the tray-shaped specimens, the topology was optimized and specimens with a honeycomb structure were also verified. Excellent mechanical strength was observed under the condition that the specimen was stretched vertically in the stacking direction and the surface was treated. The results of the tray-shaped specimens indicated that the thickness was 1.2 mm, the weight reduction rate was 20%, and the addition of a honeycomb structure could withstand an assumed bite force of 2000 N. This study suggests that the EBM system could be a useful technique for preparing custom-made titanium mesh trays of sufficient strength for mandibular reconstruction by arranging various manufacturing conditions.