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Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration., (© 2022. The Author(s).)

In oral surgery, tissue loss may occur in some cases, resulting in bone exposure and subsequent wound infection and possible scar formation during secondary healing. In this study, Terudermis ® Artificial Dermis (AD-T), a dermal defect graft made from processed bovine dermis collagen and gelatin sponge (GS) were used as dressings on 100-mm 2 wounds with exposed bone on the heads of rats. For the control group, the wound was left exposed. The wound-healing efficacy of the treatment was compared macroscopically and histologically among the three groups at 1, 2, and 4 weeks after surgery. Complete wound healing was achieved faster in the AD-T group than in the GS group, and osteoblasts appeared on the bone surface, indicating accelerated bone remodeling. Furthermore, in the AD-T group, there was an increased production of newly formed blood vessels, fibroblasts and osteoblasts positive for anti-cortactin antibodies, which are believed to contribute to wound healing. Our findings suggest that AD-T is better than GS as a wound dressing material.

Aim: Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture., Materials and Methods: We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019., Results: Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between physicians and dentists., Conclusion: The behaviour of physicians and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study., Competing Interests: Conflict of interest None disclosed., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ezrin, ERK, STAT3, and AKT are proteins that are overexpressed in various types of cancer, although their expressions in tongue cancer has received less focus. This study aimed to address associations between the expression levels of these proteins and with characteristics of the tumor and patient survival., Methods: We performed immunohistochemical staining of ezrin, ERK, STAT3, and AKT in tumors from patients with tongue carcinoma in situ (CIS, n = 17) and tongue squamous cell carcinoma (SCC, n = 46). Statistical differences between the SCC versus the CIS cohorts were estimated by calculations of bivariate odds ratios of low versus high expression of the proteins. Fisher's exact tests were used to appraise interassociations between the proteins, as well as expression levels versus patient and tumor characteristics. Survival based on Kaplan-Meier statistics in combination log-rank tests were used to address potential effects of the patient and tumor characteristics versus 5-year survival rate., Results: The relative high: low expression of all four proteins in the two cohorts differed, and particularly ERK was markedly overexpressed in the SCC versus the CIS cohort (odds ratio = 45.3, p < .01). The relative high: low expression each protein versus patient and tumor characteristics; showed associations between AKT expression and T stage (p = .002) plus node metastases (p = .12), and between ERK expression and drinking (p = .01) and smoking history (p = .01). There was no significant difference observed between ERK and the three other molecules, nor any significant difference between the degree of expression of each protein and the 5-year disease-specific survival rate., Conclusion: Ezrin, ERK, STAT3, and AKT appear to be involved in the progress from carcinoma in situ in the tongue into squamous cell carcinoma. ERK in particular is overexpressed, suggesting that ERK may be a novel therapeutic target for preventing tongue cancer., (© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase (ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbed TM with a structure resembling the loose connective tissue morphology in a novel 3D culture system. We confirmed that the 3D system using Cellbed TM accurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3D-cultured tongue cancer cell lines than in 2D cultures. Typically, under conventional 2D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells. However, in the 3D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3D culture systems using Cellbed™ are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.

Oral surgical procedures occasionally require removal of the periosteum due to lesions, and these raw bone surfaces are prone not only to infection but also to scar formation during secondary healing. The objective of this study was to identify successful methods for reconstruction using periosteal defect dressings. We created 1-cm 2 defects in the skin and cranial periosteum of 10-week-old male Wistar rats under isoflurane anesthesia. The animals were assigned to three defect treatment groups: (1) polyglycolic acid sheets with fibrin glue dressing (PGA-FG), (2) Spongel® gelatin sponge dressing (GS), and (3) open wound (control). Postoperative wound healing was histologically evaluated at 2, 4, and 6 weeks. The moist conditions maintained by the GS and PGA-FG treatments protected the bone surface from the destructive effects of drying and infection. Complete wound healing was observed in the GS group but not for all animals in the PGA-FG and control groups. Histologically, osteoblast proliferation on bone surfaces and complete epithelialization with adnexa were observed in the GS group at 6 weeks after surgery. In contrast, PGA sheets that had not been absorbed inhibited osteoblast proliferation and delayed wound healing in the PGA-FG group. Wound surface dressings maintain a moist environment that promotes wound healing, but PGA materials may not be suitable for cases involving exposed periosteum or bone surfaces due to the observed scar formation and foreign-body reaction.

Keratocystic odontogenic tumor (KCOT) is a relatively rare benign neoplasm of odontogenic origin. The squamous epithelium of KCOT usually does not contain melanocytes, however, pigmented KCOT has been documented, albeit extremely rarely. In the present study, we described an additional case of pigmented KCOT and review the clinicopathological features of this extremely rare lesion. A 23-year-old Japanese female presented with a relatively well-circumscribed round unilocular radiolucency that impacted the third molar in her right mandibula. Surgical resection was performed subsequent to a clinical diagnosis of KCOT. Histopathological study of the resected mandibular cyst showed that it was covered by a parakeratinized stratified squamous epithelium, which had slightly enlarged hyperchromatic nuclei. On the luminal surface, a wavy layer of parakeratin was observed. In addition, dendritic melanocytes without atypia were observed in approximately half of the squamous epithelium. Immunohistochemical analyses revealed that these melanocytes were positive for S-100 protein, Melan-A and HMB-45. Therefore, a diagnosis of pigmented KCOT was made. Review of the clinicopathological features of the previously reported cases of pigmented KCOT as well as the present case revealed that: i) this lesion occurs mostly in young persons (average age, 18 years) and shows female predominance; ii) most cases are solitary and involve the mandibula; and iii) the reported incidence is 0.36-10.6% and this difference may be associated with ethnicity. Thus, we described the ninth reported case of pigmented KCOT. The mechanism by which melanocytes appear and the difference in ethnic prevalence remain unclear. Additional clinicopathological studies are needed to clarify these issues.