Bone augmentation with alloplastic graft material in a patient under bisphosphonate therapy: A case report and literature review.

Cases of relatively safe dental implant treatment in patients with low-volume bisphosphonate (BP) have been gradually reported. Although bone augmentation is commonly used when the bone volume is insufficient for implant placement, the studies and case reports regarding the safety of bone augmentation in patients treated with BP remain insufficient. Herein, we report a case wherein bone augmentation was performed after BP treatment, with bone healing realized according to imaging, and we review the literature regarding BP and bone augmentation. A sixty-seven-year-old Japanese woman requested implant treatment for a hopeless lower right second molar. She had been taking minodronic acid hydrate (50 mg/4 wk) for 18 mo to treat steroid-induced osteoporosis. After obtaining informed consent, tooth extraction and bone augmentation within the extraction socket were performed. The tooth was extracted atraumatically to preserve the surrounding alveolar bone, and the extraction socket was intensely curetted. Subsequently, the socket was filled with carbonate apatite granules and covered with a biodegradable membrane, and the wound was sutured without tension. Although protracted wound healing without any symptoms of infection was observed, the wound healed completely. No clinical symptoms were observed, the color of the mucosa at the site was healthy, and imaging findings at a six month post-operation indicated that osteogenesis had progressed uneventfully.

Comparison of Skeletal Stability after Le Fort I Osteotomy With Bone Fixation Using Biodegradable and Titanium Systems: A Retrospective Study.

The titanium osteosynthesis system used for fixing bone segments after maxillary osteotomy provides reliable outcomes owing to its biocompatibility and adequate strength. In addition, several studies have evaluated the skeletal stability after maxillary osteotomy with fixation using a biodegradable system. However, the indications for applying a biodegradable system after maxillary osteotomy remain controversial. Therefore, this study aimed to compare the long-term skeletal stability of bone segments after maxillary osteotomy with bone fixation using biodegradable and titanium osteosynthesis systems and to assess the usefulness of a biodegradable osteosynthesis system. Patients who underwent Le Fort I osteotomy of the maxilla to correct jaw deformities between April 2008 and March 2021 were included in this study. A total of 45 patients were included, with 28 in the biodegradable osteosynthesis system group and 17 in the titanium group. Cephalometric and computed tomography analyses were performed to evaluate the skeletal stability of the bone segments after maxillary osteotomy with bone fixation using biodegradable or titanium osteosynthesis systems. The maxillary segment was repositioned anteriorly with a clockwise rotation. Skeletal stability was similar between the biodegradable and titanium osteosynthesis systems. Segmental changes occurred mainly in the first 6 months after surgery, and the segment was completely stable between 6 and 12 months after surgery. This study revealed no significant differences in skeletal stability after maxillary osteotomy between the biodegradable and titanium osteosynthesis systems. However, the findings in this study should be interpreted with caution owing to the small sample size and small amount of maxillary-segment movement.

Comparison of the skeletal stability after mandibular counter-clockwise rotation in three surgical procedures.

The treatment of mandibular deformities with an anterior open bite is challenging. In this study, skeletal stability after mandibular osteotomies was evaluated to determine the best treatment for mandibular prognathism with an anterior open bite in three procedures: intraoral vertical ramus osteotomy (IVRO), conventional sagittal split ramus osteotomy (conv-SSRO), and SSRO without bone fixation (nonfix-SSRO). Patients who underwent mandibular osteotomy to correct skeletal mandibular protrusion were included. Changes in skeletal and soft tissues were assessed using lateral cephalograms taken before (T1), 3 ± 2 days (T2), and 12 ± 3 months (T3) after surgery. Thirty-nine patients were included: nine in the IVRO group and 11 and 19 in the conv- and nonfix-SSRO groups, respectively. The mandibular plane angles (MPAs) of the T2-T1 were - 2.7 ± 2.0 (p = 0.0040), - 3.7 ± 1.7 (p < 0.0001), and - 2.3 ± 0.7 (p < 0.0001) in the IVRO, conv-SSRO, and nonfix-SSRO groups, respectively. The skeletal relapse of the MPAs was not related to the MPA at T2-T1, and it was approximately 1.3° in the conv-SSRO group. The skeletal relapse of the MAPs was significantly correlated with the MPA of T2-T1 in the IVRO (p = 0.0402) and non-fix-SSRO (p = 0.0173) groups. When the relapse of the MPAs was less than 1.3°, the MPA of T2-T1 was calculated as 2.5° in the nonfix-SSRO group. When the MPA of T2-T1 is less than 2.5°, non-fix SSRO may produce a reliable outcome, and when it is more than 2.5°, conv-SSRO may produce better outcomes.

A Prospective Study of the Assessment of the Efficacy of a Biodegradable Poly(l-lactic acid/ε-caprolactone) Membrane for Guided Bone Regeneration.

Biodegradable guided bone regeneration (GBR) membranes consist primarily of collagen and aliphatic polyesters. This study assessed the comparative efficacy of a poly(l-lactic-caprolactone) [P(LA/CL)] membrane versus that of a collagen membrane in GBR. Patients requiring GBR simultaneously or before dental implant placement in edentulous regions were randomly assigned to one of two membranes. Within each membrane, they were subdivided into 3 groups: dental implants were placed simultaneously with GBR in groups A and B, and 180 days post-GBR in group C. The augmented bone width was measured at 1, 3, and 6 mm from the implant's neck (groups A and B) or the reference line (group C), utilizing cone-beam computed tomography images, immediately and 150 days post-surgery. A histological study was performed to evaluate bone formation in group C. No adverse events were observed. In the collagen group, the absorbed ratios of the augmented bone were 40.9 ± 36.7%, 29.4 ± 30.1%, and 11.1 ± 22.0% at 1, 3, and 6 mm, respectively; the ratio at 6 mm was significantly lower than that at 1 mm (p = 0.0442). In the P(LA/CL) group, those were 26.2 ± 27.3%, 17.1 ± 19.7%, and 13.3 ± 16.4% at 1, 3, and 6 mm, respectively, with no significant difference at each point. No significant inter-membrane differences were observed. The bone augmentation potential of the P(LA/CL) membrane matched that of the collagen membrane. P(LA/CL) could be used as a safe and effective membrane in GBR.

Occlusal Plane Angle as a Key Factor for Chin Protrusion After Mandibular Osteotomy in Skeletal Class III.

There is no treatment algorithm to decide whether maxillomandibular or mandibular osteotomy alone should be performed in borderline cases. This study assessed the factors that affect the changes in soft tissue after mandibular setback. Patients who underwent mandibular osteotomy alone to correct mandibular protrusion were included in this study. Hard and soft tissue analyses were performed on lateral cephalograms before and 12±3 months after surgery. The popular points were set for referencing hard and soft tissues on the lateral cephalogram. Nasolabial, labiomental, and soft tissue facial plane angles were measured for the soft tissue assessment. To assess the mandibular setback amount, SNB was calculated. Twenty-one patients were included in this study. The nasolabial angle was increased after surgery and its change significantly correlated with the change in SNB ( P =0.00815). The change in soft tissue facial plane angle after surgery per change in SNB significantly correlated with the occlusal plane angle ( P =0.0009). An occlusal plane angle of at least 15.45 degrees was required for the SNB and soft tissue facial plane angle to change to the same degree. The occlusal plane angle (whether or not it was ≥15.45 degrees) may help in determining the surgical approach in borderline cases, specifically on whether maxillomandibular or mandibular osteotomy alone should be performed if the mandibular setback is simple.

Immunomodulatory Macrophages Enable E-MNC Therapy for Radiation-Induced Salivary Gland Hypofunction.

A newly developed therapy using effective-mononuclear cells (E-MNCs) is reportedly effective against radiation-damaged salivary glands (SGs) due to anti-inflammatory and revascularization effects. However, the cellular working mechanism of E-MNC therapy in SGs remains to be elucidated. In this study, E-MNCs were induced from peripheral blood mononuclear cells (PBMNCs) by culture for 5-7 days in medium supplemented with five specific recombinant proteins (5G-culture). We analyzed the anti-inflammatory characteristics of macrophage fraction of E-MNCs using a co-culture model with CD3/CD28-stimulated PBMNCs. To test therapeutic efficacy in vivo, either E-MNCs or E-MNCs depleted of CD11b-positive cells were transplanted intraglandularly into mice with radiation-damaged SGs. Following transplantation, SG function recovery and immunohistochemical analyses of harvested SGs were assessed to determine if CD11b-positive macrophages contributed to tissue regeneration. The results indicated that CD11b/CD206-positive (M2-like) macrophages were specifically induced in E-MNCs during 5G-culture, and Msr1- and galectin3-positive cells (immunomodulatory macrophages) were predominant. CD11b-positive fraction of E-MNCs significantly inhibited the expression of inflammation-related genes in CD3/CD28-stimulated PBMNCs. Transplanted E-MNCs exhibited a therapeutic effect on saliva secretion and reduced tissue fibrosis in radiation-damaged SGs, whereas E-MNCs depleted of CD11b-positive cells and radiated controls did not. Immunohistochemical analyses revealed HMGB1 phagocytosis and IGF1 secretion by CD11b/Msr1-positive macrophages from both transplanted E-MNCs and host M2-macrophages. Thus, the anti-inflammatory and tissue-regenerative effects observed in E-MNC therapy against radiation-damaged SGs can be partly explained by the immunomodulatory effect of M2-dominant macrophage fraction.

Fixation of an orthodontic anchor screw using beta-tricalcium phosphate in a screw-loosening model in rats.

OBJECTIVES: To create an orthodontic anchor screw (OAS)-loosening model and to investigate whether filling the bone hole with beta-tricalcium phosphate (ß-TCP) can fix the OAS against orthodontic force. MATERIALS AND METHODS: Bone holes with different diameters (1.6, 2.1, or 2.5 mm) were drilled in the tibias of 11-week-old male Wistar rats, and an OAS (3.0 mm in length and 1.2 mm in diameter) was inserted. After a healing period of 2 or 4 weeks, orthodontic force was applied, and the diameter of the bone hole appropriate for the loosening model was determined. Subsequently, under the loosening model, the bone hole was filled with ß-TCP, orthodontic force was applied, and movement of the OAS and surrounding tissue changes were evaluated by micro-computed tomography images and histological specimen analysis. RESULTS: The bone hole of 1.6 mm in diameter was employed as the OAS-loosening model. When ß-TCP was inserted into the bone hole, the linear distance and mesial tipping angle of the OAS movement decreased markedly. Furthermore, the values of bone morphometry significantly increased with ß-TCP filling. CONCLUSIONS: An OAS-loosening model was established in rats and demonstrated that the loosening OAS was stabilized by ß-TCP filling through bone formation. ß-TCP may be useful for fixation of a loosening OAS.

First-in-Human Study to Investigate the Safety Assessment of Peri-Implant Soft Tissue Regeneration with Micronized-Gingival Connective Tissue: A Pilot Case Series Study.

Background: We have recently proposed an alternative strategy of free gingival graft (FGG) and connective tissue graft (CTG) using micronized-gingival connective tissues (MGCTs). The advantage of this strategy is that MGCTs from a small piece of maxillary tuberosity can regenerate the keratinized tissue band. However, safety and efficacy have not yet been established in patients. This clinical study was a pilot case series, and the objective was to assess the safety and the preliminary efficacy of MGCTs on peri-implant mucosa regeneration. Methods: This was a pilot interventional, single-center, first-in-human (FIH), open (no masking), uncontrolled, and single-assignment study. A total of 4 patients who needed peri-implant soft tissues reconstruction around dental implants received transplantation of atelocollagen-matrix with MGCTs micronized by the tissue disruptor technique. The duration of intervention was 4 weeks after surgery. Results: This first clinical study demonstrated that using MGCTs did not cause any irreversible adverse events, and it showed the preliminary efficacy for peri-implant soft tissues reconstruction in dental implant therapy. Conclusions: Though further studies are needed on an appropriate scale, as an alternative strategy of FGG or CTG, MGCTs might be promising for peri-implant mucosa reconstruction without requiring a high level of skills and morbidity to harvest graft tissues.

Long-term effect of photodynamic therapy on oral squamous cell carcinoma and epithelial dysplasia.

BACKGROUND: Oral squamous cell carcinoma (OSCC) treatment consists mainly of surgery, chemotherapy, and radiotherapy, alone or in combination. Epithelial dysplasia (ED) is also treated with surgery. However, these treatments can induce functional and/or aesthetic disturbances. Photodynamic therapy (PDT) can preserve organs. Although short-term studies have shown good progress, long-term evaluations have not yet been conducted. This study aimed to clarify the long-term effects of PDT on OSCC and ED. METHODS: Patients who underwent PDT with the first (porfimer sodium) or second generation photosensitizers (talaporfin sodium) for early OSCC (T1 and T2) and ED were included in this study. The long-term prognosis was assessed. RESULTS: Twenty-three patients were included. Complete response (CR) was observed in 19 patients (82.6%) and partial response (PR) in 4 patients (17.4%) 4 weeks after PDT. Regarding long-term progress, local region recurrence occurred in 11 of 19 CR cases (57.9%), and the term of recurrence was 27.4 ± 30.4 months. Surgical resection was performed in all local recurrence and PR cases, and 3 patients died of the underlying disease. CONCLUSIONS: PDT provides a good outcome in the short term, but its long-term effects are limited.

Remarkably Elongated Coronoid Processes: A Cadaveric Case Report.

An elongated coronoid process (ECP) can lead to impingement of the coronoid process on the body or arch of the zygomatic bone when opening the mouth. The etiology of ECP is unclear, but several theories have been postulated. We present a case of an ECP found in a 63-year-old in a Caucasian cadaveric specimen. The length of the coronoid process was 26.6 mm on the left side and 26.3 mm on the right side. To our knowledge, this is the longest coronoid process reported in the extant literature. The details of this case and the clinical significance are discussed.

Application of the sliding window method and Mask-RCNN method to nuclear recognition in oral cytology.

BACKGROUND: We aimed to develop an artificial intelligence (AI)-assisted oral cytology method, similar to cervical cytology. We focused on the detection of cell nuclei because the ratio of cell nuclei to cytoplasm increases with increasing cell malignancy. As an initial step in the development of AI-assisted cytology, we investigated two methods for the automatic detection of cell nuclei in blue-stained cells in cytopreparation images. METHODS: We evaluated the usefulness of the sliding window method (SWM) and mask region-based convolutional neural network (Mask-RCNN) in identifying the cell nuclei in oral cytopreparation images. Thirty cases of liquid-based oral cytology were analyzed. First, we performed the SWM by dividing each image into 96 × 96 pixels. Overall, 591 images with or without blue-stained cell nuclei were prepared as the training data and 197 as the test data (total: 1,576 images). Next, we performed the Mask-RCNN by preparing 130 images of Class II and III lesions and creating mask images showing cell regions based on these images. RESULTS: Using the SWM method, the highest detection rate for blue-stained cells in the evaluation group was 0.9314. For Mask-RCNN, 37 cell nuclei were identified, and 1 cell nucleus was identified as a non-nucleus after 40 epochs (error rate:0.027). CONCLUSIONS: Mask-RCNN is more accurate than SWM in identifying the cell nuclei. If the blue-stained cell nuclei can be correctly identified automatically, the entire cell morphology can be grasped faster, and the diagnostic performance of cytology can be improved.

Influence of different treatment procedures on the temporomandibular joint after mandibular setback in skeletal class III - A retrospective study.

The aim of this study was to clarify the effects of three different orthognathic surgical procedures on the temporomandibular joint after mandibular setback. Conventional sagittal split ramus osteotomy (SSRO) with segmental fixation (conv-SSRO), intraoral vertical ramus osteotomy (IVRO), or SSRO without fixation followed by the physiological positioning strategy (nonfix-SSRO) was performed for mandibular setback. Temporomandibular joint disorder (TMD) symptoms were clinically assessed, and the condylar head angle was measured. In total, 129 patients participated. Preoperative TMD and treatment procedure were related to postoperative TMD. A menton deviation of 3.43 mm was the cutoff for the risk of postoperative TMD. The incidence rate of postoperative TMD in the conv-SSRO group was higher than that in the IVRO (p = 0.0197) and nonfix-SSRO (p = 0.0001) groups in asymmetric cases. There was no significant postoperative change in the temporomandibular joint space in each group. In symmetric and asymmetric cases, the condylar head was rotated inwards by 5.82 ± 4.75° (p < 0.0001) and 5.44 ± 3.10° (p < 0.0001), respectively, in the conv-SSRO group, and outwards by -7.98 ± 5.05° (p < 0.0001) and -8.32 ± 6.38° (p < 0.0001), respectively, in the IVRO group, but it was almost stable in the nonfix-SSRO group. Within the limitations of the study it seems that nonfix-SSRO should be preferred over conv-SSRO and IVRO whenever appropriate.

Clinical Efficacy and Safety of Antimicrobial Photodynamic Therapy in Residual Periodontal Pockets during the Maintenance Phase.

Antimicrobial photodynamic therapy (a-PDT) in combination with scaling root planing (SRP) is more effective at improving periodontal status than SRP alone. However, the effectiveness of a-PDT in combination with irrigation for patients undergoing periodontal maintenance has not been clarified. This study evaluated the efficacy and safety of a-PDT in the maintenance phase. Patients who had multiple sites with bleeding on probing (BOP) and periodontal probing depth (PPD) of 4-6 mm in the maintenance phase were treated with a split-mouth design. These sites were randomly assigned to one of two groups: the a-PDT group and the irrigation group. In the a-PDT group, the periodontal pockets were treated with light-sensitive toluidine blue and a light irradiator. In the irrigation group, the periodontal pockets were simply irrigated using an ultrasonic scaler. After 7 days, the safety and efficacy of a-PDT were assessed. The mean PPD of the a-PDT group had reduced from 4.50 mm to 4.13 mm, whereas negligible change was observed in the irrigation group. BOP significantly improved from 100% to 33% in the PDT group, whereas it hardly changed in the irrigation group. No adverse events were observed in any patients. a-PDT may be useful as a noninvasive treatment in the maintenance phase, especially in patients with relatively deep periodontal pocket.

Long-term clinical and radiographic evaluation after maxillary sinus floor augmentation with octacalcium phosphate-collagen composite: A retrospective case series study.

The purpose of this study was to evaluate, using clinical and radiological assessments, the stability of dental implants 5 years after maxillary sinus floor augmentation with octacalcium phosphate-collagen composite (OCP/Col). Maxillary sinus floor augmentation was performed through a lateral window approach. Depending on the height of the host bone, a simultaneous approach (≥5 mm) or a staged approach (less than 5 mm) was employed. The primary outcome was the evaluation of clinical dental implant conditions such as infection, peri-implantitis, dental implant stability, pain, and paresthesia. Secondary outcomes were the evaluation of the augmented bone volume, change rate of augmented bone volume, vertical bone height, and marginal bone loss around dental implant fixture. The conditions of all dental implants were uneventful throughout the follow-up period. Augmented bone volume and changing rate of augmented bone volume were essentially unchanged following maturation of the OCP/Col-derived new bone. The change rate of new bone volume was 21.9% in the simulated approach and 16.8% in the staged approach at 1 year and 5 years postoperatively. The reduction rate in vertical bone height was 7.1% in the simultaneous approach and 7.5% in the staged approach between 1 year and 5 years postoperatively. Mean marginal bone loss was 1.76 mm with the simultaneous approach, and 0.50 mm with the staged approach at 5 years postoperatively. In conclusion, the success of dental implants 5 years after sinus floor augmentation by OCP/Col implantation was clarified by both clinical and radiological evaluations.

Safety and feasibility assessment of biodegradable poly (l-lactic acid/ε-caprolactone) membrane for guided bone regeneration: A case series of first-in-human pilot study.

BACKGROUND/PURPOSE: Guided bone regeneration (GBR) is the most popular technique for alveolar ridge augmentation in implant dentistry, and resorbable cell barrier membrane, made of collagen, is widely used. We tried to develop a new resorbable cell barrier membrane from an animal-free product. This study aimed to investigate the safety and feasibility for clinical application of poly (l-lactic acid/ε-caprolactone) [P (LA/CL)] membrane, a novel biodegradable synthetic material used for GBR. MATERIALS AND METHODS: Patients who required horizontal bone augmentation (≥3 mm implant exposure) for implant treatment were included in the study. P (LA/CL) membrane was used simultaneously with implant placement to achieve bone augmentation by GBR. The occurrence of adverse events was assessed until the follow-up period of a second surgical procedure. The amount of bone augmentation was assessed by means of cone-beam computed tomography, and implant stability was assessed by measuring the implant stability quotient (ISQ). Student's t-test was used and the level of significance was set at p < 0.05. RESULTS: This first-in-human study comprised five participants. Adverse events were observed in three of five patients, and a cause-and-effect relationship of the membrane could not be denied in one of them. Good bone formation was observed in the GBR region of all five patients. The ISQ during the second surgical procedure indicated good osseointegration in all the patients. CONCLUSION: The application of P (LA/CL) membrane for bone augmentation with GBR made it possible to maintain the augmented bone volume without causing any irreversible adverse events. However, further investigations on humans are required to confirm the safety of this biomaterial.

Application of hydroxyapatite/collagen composite material for maxillary sinus floor augmentation.

The aim of this study was to clarify whether hydroxyapatite/collagen composite material (HAp/Col) could be useful as a graft material for maxillary sinus floor augmentation (MSFA). MSFA and implant placement were performed simultaneously. When the lateral approach was employed, 3 out of 19 implants failed in 3 maxillary sinuses (success rate; 84.2%), and in these cases the alveolar bone heights, cortical bone thicknesses and values of the implant stability quotient were smaller. If alveolar the bone height, cortical bone thickness, and healing period are optimized, HAp/Col can be a useful graft material for MSFA.

Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle.

Muscle stem cells (satellite cells) are distributed throughout the body and have heterogeneous properties among muscles. However, functional topographical genes in satellite cells of adult muscle remain unidentified. Here, we show that expression of Homeobox-A (Hox-A) cluster genes accompanied with DNA hypermethylation of the Hox-A locus was robustly maintained in both somite-derived muscles and their associated satellite cells in adult mice, which recapitulates their embryonic origin. Somite-derived satellite cells were clearly separated from cells derived from cranial mesoderm in Hoxa10 expression. Hoxa10 inactivation led to genomic instability and mitotic catastrophe in somite-derived satellite cells in mice and human. Satellite cell-specific Hoxa10 ablation in mice resulted in a decline in the regenerative ability of somite-derived muscles, which were unobserved in cranial mesoderm-derived muscles. Thus, our results show that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating region-specific pathophysiology in adult muscles.

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study.

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at -20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size.

Assessment of safety and efficacy of antimicrobial photodynamic therapy for peri-implant disease.

BACKGROUND: There is no reliable treatment procedure for peri-implant disease, despite the rise in its incidence. This study sought to evaluate the short-term safety and efficacy of antimicrobial photodynamic therapy (a-PDT) on peri-implantitis by assessing the volume of pus discharge after a-PDT. METHODS: Patients with pus discharge from a peri-implant pocket were recruited from December 1st, 2019 to April 30th, 2020. The enrolled implants were randomly assigned to one of two groups, the irrigation and a-PDT groups. Their peri-implant pocket was irrigated with normal saline in the irrigation group, and a saline irrigation and subsequent a-PDT with toluidine blue (TB) was performed in the a-PDT group. The safety and efficacy of a-PDT were assessed 7 days after treatment. RESULTS: Twenty-five implants in 21 patients (irrigation group; 13 implants, a-PDT group; 12 implants) were registered. No complication was observed after a-PDT. Pus discharge was decreased in 7 of 12 implants (58.3 %) in the a-PDT group, and in 2 of 13 implants (15.4 %) in the irrigation group. According to Fisher's exact test, a-PDT resulted in a statistically significant decrease in pus discharge compared to irrigation alone (p = 0.0414). CONCLUSIONS: a-PDT was confirmed to be a safe treatment for peri-implantitis, and the short-term efficacy of a-PDT with TB on peri-implantitis was clarified. Nevertheless, its efficacy remains restricted, and a new combination therapy of a-PDT and decontamination procedures is expected to be developed in future.

Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia).

BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057.