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.

Bcl2l1 Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis.

Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generated osteoblast-specific Bcl2l1-deficient (Bcl2l1fl/flCre) mice using 2.3-kb Col1a1 Cre. Trabecular bone volume and the trabecular number were lower in Bcl2l1fl/flCre mice of both sexes than in Bcl2l1fl/fl mice. In bone histomorphometric analysis, osteoclast parameters were increased in Bcl2l1fl/flCre mice, whereas osteoblast parameters and the bone formation rate were similar to those in Bcl2l1fl/fl mice. TUNEL-positive osteoblastic cells and serum TRAP5b levels were increased in Bcl2l1fl/flCre mice. The deletion of Bcl2l1 in osteoblasts induced Tnfsf11 expression, whereas the overexpression of Bcl-XL had no effect. In a co-culture of Bcl2l1-deficient primary osteoblasts and wild-type bone-marrow-derived monocyte/macrophage lineage cells, the numbers of multinucleated TRAP-positive cells and resorption pits increased. Furthermore, serum deprivation or the deletion of Bcl2l1 in primary osteoblasts increased apoptosis and ATP levels in the medium. Therefore, the reduction in trabecular bone in Bcl2l1fl/flCre mice may be due to enhanced bone resorption through osteoblast apoptosis and the release of ATP from apoptotic osteoblasts, and Bcl2l1 may inhibit bone resorption by preventing osteoblast apoptosis.

Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation.

Salivary gland (SG) hypofunction is a common post-radiotherapy complication. Besides the parenchymal damage after irradiation (IR), there are also effects on mesenchymal stem cells (MSCs) which were shown to contribute to regeneration and repair of damaged tissues by differentiating into stromal cell types or releasing vesicles and soluble factors supporting the healing processes. However, there are no adequate reports about their roles during SG damage and regeneration so far. Using an irradiated SG mouse model, we performed certain immunostainings on tissue sections of submandibular glands at different time points after IR. Immunostaining for CD31 revealed that already one day after IR, vascular impairment was induced at the level of capillaries. In addition, the expression of CD44-a marker of acinar cells-diminished gradually after IR and, by 20 weeks, almost disappeared. In contrast, the number of CD34-positive cells significantly increased 4 weeks after IR and some of the CD34-positive cells were found to reside within the adventitia of arteries and veins. Laser confocal microscopic analyses revealed an accumulation of CD34-positive cells within the area of damaged capillaries where they were in close contact to the CD31-positive endothelial cells. At 4 weeks after IR, a fraction of the CD34-positive cells underwent differentiation into α-SMA-positive cells, which suggests that they may contribute to regeneration of smooth muscle cells and/or pericytes covering the small vessels from the outside. In conclusion, SG-resident CD34-positive cells represent a population of progenitors that could contribute to new vessel formation and/or remodeling of the pre-existing vessels after IR and thus, might be an important player during SG tissue healing.

Do not keep it simple: recent advances in the generation of complex organoids.

3D cell culture models which closely resemble real human tissues are of high interest for disease modelling, drug screening as well as a deeper understanding of human developmental biology. Such structures are termed organoids. Within the last years, several human organoid models were described. These are usually stem cell derived, arise by self-organization, mimic mechanisms of normal tissue development, show typical organ morphogenesis and recapitulate at least some organ specific functions. Many tissues have been reproduced in vitro such as gut, liver, lung, kidney and brain. The resulting entities can be either derived from an adult stem cell population, or generated from pluripotent stem cells using a specific differentiation protocol. However, many organoid models only recapitulate the organs parenchyma but are devoid of stromal components such as blood vessels, connective tissue and inflammatory cells. Recent studies show that the incorporation of endothelial and mesenchymal cells into organoids improved their maturation and might be required to create fully functional micro-tissues, which will allow deeper insights into human embryogenesis as well as disease development and progression. In this review article, we will summarize and discuss recent works trying to incorporate stromal components into organoids, with a special focus on neural organoid models.

Full Regeneration of Maxillary Alveolar Bone Using Autogenous Partially Demineralized Dentin Matrix and Particulate Cancellous Bone and Marrow for Implant-Supported Full Arch Rehabilitation.

Autogenous partially demineralized dentin matrix (APDDM) has been reportedly used as a superior bone graft material. A 52-year-old Japanese man who exhibited severe periodontitis was referred for oral rehabilitation. He underwent wide-range anterior maxillary alveolar bone and bilateral sinus floor augmentation by grafting of a mixture of APDDM and particulate cancellous bone and marrow (PCBM); subsequently, he underwent implant-supported full arch rehabilitation. He has been followed up for 4 years after placement of the final restoration without any complications, and his physiological bone volume has been maintained. APDDM constitutes an alternative treatment that may increase the volume of graft material and might prevent rapid resorption of PCBM, because APDDM served as a scaffold for osteoblasts from PCBM. When possible, it may be useful to apply APDDM as a graft material with PCBM for large-volume alveolar bone regeneration.

Alveolar bone preservation by a hydroxyapatite/collagen composite material after tooth extraction.

OBJECTIVE: The aim of this study was to assess the effectiveness of a hydroxyapatite/collagen composite material (HAp/Col) for preservation of alveolar bone after tooth extraction. MATERIALS AND METHODS: HAp/Col was applied to the alveolus bone ridge preservation after tooth extraction, because of subsequent dental implant placement in 35 regions of 24 patients (mean age, 59.3 years; range, 25-81 years). Cone beam computed tomography was used to assess changes in alveolar bone at the extraction site before and at 3 months (mean, 13.7 weeks; range, 10-17 weeks) after tooth extraction. Changes in height and width of the alveolar bone were measured to evaluate bone reduction after surgery. Bone biopsy was performed at 11 regions of dental implant placement to observe bone regeneration and remaining material in the extraction socket. RESULTS: The alveolar bone height was decreased by 0.00 ± 2.44 mm at the buccal side and 0.35 ± 1.73 mm at the lingual side, while the width was decreased by 1.02 ± 1.64 mm at 3 months after surgery. The middle of the socket floor was elevated by 5.71 ± 3.45 mm at 3 months after surgery. Bone biopsy specimens revealed no remaining implanted material, and approximately 49.79 ± 14.41% of the specimens were occupied by bone tissue. CONCLUSIONS: According to the result of this study, HAp/Col is a reliable material to presearve alveolar bone after tooth extraction. CLINICAL RELEVANCE: HAp/Col contributes dental implant treatment due to maintain the alveolar bone after tooth extraction.

Soft tissue engineering with micronized-gingival connective tissues.

The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability.

Clinical study of guided bone regeneration with resorbable polylactide-co-glycolide acid membrane.

The guided bone regeneration (GBR) technique is often applied to provide sufficient bone for ideal implant placement. The objective of this study was to evaluate whether GC membrane®, which has already been used for guided tissue regeneration (GTR), can also be available for GBR. Twenty-three implants in 18 patients were evaluated in the study. All patients underwent implant placement with GBR using GC membrane®. Cone-beam computed tomography was performed at 13-30 weeks after surgery and the amount of augmented bone was assessed. The implant stability quotient (ISQ) was measured at the second operation to evaluate implant stability. Although wound dehiscence was observed at 4 of 23 regions (17.4%), all wounds closed quickly without any events by additional antibiotic administration. GBR-induced bone augmentation of 0.70-2.56 mm horizontally and 0-6.82 mm vertically. Only 0.18 mm of bone recession was observed at 16-24 months after implant placement. GBR with GC membrane® induced sufficient bone augmentation, leading to successful implant treatment. The present results suggest that GC membrane® is available not only for GTR, but also for GBR.

Low-serum culture with novel medium promotes maxillary/mandibular bone marrow stromal cell proliferation and osteogenic differentiation ability.

OBJECTIVES: The purpose of this study was to evaluate the effect of low-serum STK2 medium on the isolation and osteogenic differentiation of human maxillary/mandibular bone marrow stromal cells (MBMSCs). MATERIALS AND METHODS: Human MBMSCs were obtained from patients undergoing dental implant treatment. These cells were cultured in serum-free medium or STK2 medium containing 1  % fetal bovine serum (low-serum) or α-MEM containing 10  % fetal bovine serum (control). Proliferation on the culture surface, cell surface antigen expression, and mRNA levels of neural crest and osteogenic markers were examined. Alkaline phosphatase assay and Alizarin red staining were used to assess osteogenic differentiation potential. Immunoblotting analysis was performed to detect ERK phosphorylation. RESULTS: Low-serum and control MBMSCs were positive for CD73, CD90, and CD105 and negative for CD14, CD34, CD45, CD271, and HLA-DR. CD140a was absent in low-serum cells but present in control cells. Low-serum MBMSCs proliferated more than control MBMSCs. After induction of osteogenic differentiation, alkaline phosphatase activity and osteocalcin mRNA levels were higher in low-serum MBMSCs than in control cells, and Alizarin red staining was stronger in low-serum MBMSCs than in control cells. Low-serum culture promoted ERK phosphorylation. CONCLUSIONS: MBMSCs precultured in low-serum medium exhibited a greater cumulative cell number and a higher osteogenic differentiation capacity than those cultured in control medium. CLINICAL RELEVANCE: These findings indicate that low-serum STK2 culture might be useful to promote MBMSC proliferation and osteogenic differentiation. This method requires less autologous blood collection for cell expansion than conventional methods, thus reducing the burden on patients.

Soft tissue changes after a mandibular osteotomy for symmetric skeletal class III malocclusion.

The soft tissue profile is crucial to esthetics after orthognathic surgery. The aim of this study was to assess the soft tissue changes of the subnasal and submental regions more than 1 year after a sagittal split ramus osteotomy (SSRO) in patients with skeletal class III malocclusion. A total of 22 patients with mandibular prognathism were included in this study. Patients had lateral cephalograms before and more than 1 year after they underwent an isolated SSRO. Soft and hard tissue changes were assessed using the lateral cephalograms. The lower lip, labiomenton, and soft tissue menton moved posteriorly by 85, 89, and 88% compared with the corresponding hard tissue, and the movement of the soft tissue B point and the top of the chin nearly reflected the displacement of the hard tissues, at 96 and 99%, respectively. The labiomenton, stomions, and naso-labial angles were changed after the mandibular set-back and the changes in these angles correlated with either the width of the soft tissue or skeletal displacement. The naso-labial angle could be altered even if an isolated mandibular osteotomy is performed. Changes to the stomions and naso-labial angles were affected by hard tissue movement, while changes to the labiomental angle were affected by the width of the soft tissue after the mandibular osteotomy. It is important to create an accurate preoperative prediction of the esthetic outcomes after a mandibular osteotomy by considering the interrelations between the hard and soft tissues.

Sonographic Evaluation of Bone Formation After Sagittal Split Ramus Osteotomy.

OBJECTIVES: The aim of this study was to assess the applicability of sonography for evaluation of mandible bone healing after orthognathic surgery. METHODS: The study included 10 patients who underwent orthognathic surgery. To assess new bone formation after sagittal split ramus osteotomy, the echo intensities of ultrasound (US) reflections of the proximal segment, distal segment, and bone gap were measured with a real-time US scanner at 1 day, 1, 2, 3, and 4 weeks, and 2 and 4 months postoperatively. RESULTS: The mean echo intensity of US reflections of the bone gap gradually increased and became equivalent to that of bone surfaces by 4 weeks postoperatively. X-ray tomograms confirmed bone formation at the bone gap at the same time. CONCLUSIONS: This study indicates that sonography may be useful for evaluating osseous healing after orthognathic surgery.

Bimaxillary Osteotomy for Jaw Deformity With Facioscapulohumeral Muscular Dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a subtype of muscular dystrophies which reduces the muscle strength, especially the regions of scapular, shoulder, and upper arms, progressively. According to progressive muscle weakness in FSHD, postoperative stability of patient with FSHD after orthognathic surgery is not reliably acquired same as healthy subjects. A 32-year-old woman with FSHD underwent orthodontic and orthognathic surgical treatment due to jaw deformity. She has been followed up more than 3 years after surgery and acquired skeletal stability. This patient is the first report that showed long-term skeletal stability after orthognathic surgery in patient with FSHD. This patient report suggests that it is possible to apply orthognathic surgical treatment to patients with FSHD.

Secondary bone grafting with simultaneous auto-tooth transplantation to the alveolar cleft.

One of the most important purposes of secondary bone grafting of the alveolar cleft is to stabilize the maxillary alveolar arch with completion of the dental arch. We report a case of secondary bone grafting with simultaneous auto-tooth transplantation to the alveolar cleft, using particulate cancellous bone and marrow (PCBM) combined with platelet-rich plasma (PRP), which contains many growth factors. The patient was born with a bilateral cleft lip and left buccal-localized cleft alveolus. We performed bone grafting to the cleft using PCBM with PRP and transplantation of the supernumerary tooth under general anesthesia when the patient was aged 11 years, 10 months. The postoperative course was uneventful and without any complications. The orthodontic treatment was nearly complete 10 months after the operation. The transplanted tooth was stable, and a normal gingival contour was attained during the 2-year follow-up period. The case was successful in achieving a stable occlusal condition within a short period. We suggest secondary bone grafting with simultaneous auto-tooth transplantation as an option for alveolar cleft treatment.

Effects of Vertical Movement of the Anterior Nasal Spine on the Maxillary Stability After LeFort I Osteotomy for Pitch Correction.

Few reports have so far evaluated the maxillary stability after LeFort I osteotomy (L-1) for pitch correction. In the current study, the authors assessed the SN-PP (palatal plane) to evaluate the skeletal stability after osteotomy with clockwise or counter-clockwise rotation and investigated the effects of anterior nasal spine (ANS) and posterior nasal spine (PNS) movement on the stability of the SN-PP.The SN-PP and the positions of ANS, PNS, and point A were measured on lateral cephalograms before surgery (T1), immediately after surgery (T2), and more than 1 year after surgery (T3).All measured angle and points were stable in 4 cases of counter-clockwise rotation. In the 16 cases of clockwise rotation, T3-T2 of SN-PP, ANS, and point A was -2.05°, -2.56 mm, and -1.64 mm, when the SN-PP increased more than 4° after osteotomy. When the ANS moved downward more than 3 mm, the ANS and point A relapsed significantly by 2.75 and 2.31 mm, while the SN-PP relapsed 1.61° more than 1 year after surgery.When the SN-PP increased by more than 4° or the ANS moved downward by more than 3 mm, the authors suggest shifting the PNS upward instead of moving the ANS downward.

A case of glandular odontogenic cyst in the mandible treated with the dredging method.

Glandular odontogenic cyst (GOC) is a rare odontogenic cyst derived from the odontogenic epithelium. GOC shows unpredictable and potentially aggressive behavior. Although enucleation and curettage are applied in most cases, the recurrence rate remains relatively high. Because a standard care procedure for GOC has not been established, we propose a new treatment procedure for GOC. In this case report, we describe a 62-year-old Japanese woman who suffered from GOC arising at the anterior region of her mandible and who was treated using the dredging method. She underwent enucleation and curettage twice using the dredging method with preservation of the teeth, which were involved with the lesion, but the lesion recurred 2 years later. In addition to enucleation and curettage, apicoectomy of the teeth was performed with a third dredging method procedure, and prognosis has been good with no recurrence for 18 months since the last treatment.

Oral Rehabilitation With Orthognathic Surgery After Dental Implant Placement for Class III Malocclusion With Skeletal Asymmetry and Posterior Bite Collapse.

Increasing numbers of older patients are seeking orthognathic surgery to treat jaw deformity. However, orthodontic and orthognathic surgical treatment is difficult in cases without occlusal vertical stop. A 55-year-old man presented with Class III malocclusion and mandibular protrusion including esthetic problems and posterior bite collapse. He underwent dental implant treatment to reconstruct an occlusal vertical stop before orthognathic surgery. His occlusal function and esthetic problems improved after surgery, and his skeletal and occlusal stability has been maintained for 6 years. Dental implant placement at appropriate positions could help to determine the position of the proximal segment at orthognathic surgery and could shorten the time required to restore esthetic and occlusal function. This case demonstrates how skeletal and dental stability can be maintained long after surgery in a patient with jaw deformity and posterior bite collapse.

The three-dimensional assessment of dynamic changes of the proximal segments after intraoral vertical ramus osteotomy.

OBJECTIVES: The aim of this study was to assess the positional changes of the proximal segments after intraoral vertical ramus osteotomy (IVRO). METHOD: Fifteen patients underwent IVRO and were followed according to the authors' unique postoperative management regimen. The analyses of the positions and angles of the proximal segments were performed on frontal and lateral cephalograms, which were taken before surgery (T1) and within 3 days (T2), at 4 weeks (T3), and later than 6 months after surgery (T4). The three-dimensional positions of the condylar heads were also assessed by CT images, which were taken before and 1 year after surgery. RESULTS: The proximal segments temporarily swung posteriorly and laterally with a center on the condylar head as a fulcrum point at T2 and T3, compared with T1, and they repositioned at T4. The condylar heads moved inferior approximately 2 mm with lateral rotation one year after surgery, as seen in the CT. DISCUSSION: The condylar heads changed their positions physiologically for newly established jaw movement after IVRO with the authors' post-operative management regimen because the post-operative skeletal stability and the jaw function were good and stable using this method.

Long-term follow-up after reimplantation of tumorous mandible bone treated with combination of decalcification and lyophilization.

Mandibular resection requires reconstruction, with often unsatisfactory morphofunctional results. Reimplantation of the resected mandible itself is one of ideal solutions to this problem. However, both devitalization of tumor cells involved in resected bone and preservation of osteoinductive activity are required for successful results. Lyophilization appears to enable devitalization of tumor cells, and decalcified bone implants are likely to have osteoinductive potential. Accordingly, we speculated that decalcification and lyophilization of resected bone would be an appropriate method for mandibular reconstruction. However, there is no study on the reimplantation of mandibles treated with these methods to date. The purpose of this study was to estimate the long-term follow-up of reimplanted mandibles treated with decalcification and lyophilization. Presented here are 2 patients of reimplanted mandibles treated by decalcification and lyophilization who were followed up for 8 and 9 years. We observed a good incorporation of the graft in 1 case, but severe absorption in the other. Our results suggest that treatment with decalcification and lyophilization is 1 strategy for reimplantation of the resected bone in mandibular reconstruction, but further study is needed to prevent absorption of the reimplanted bone over the long term.

The migration pathway of an extracted maxillary third molar into the buccal fat pad.

The migration of the maxillary third molar is one of the most critical complications that can occur during extraction, and the most frequent site of migration is the maxillary sinus. We herein report an extremely rare case in which the migrated maxillary third molar became displaced into the buccal fat pad. The pathway of migration from the original site of the tooth into the buccal space is therefore considered from the anatomical perspective in this paper.

GDFs promote tenogenic characteristics on human periodontal ligament-derived cells in culture at late passages.

Tendon/ligament injures are leading disabilities worldwide. The periodontal ligament (PDL) connects teeth to bone, and is comparable to a tendon/ligament-to-bone insertion. PDL-derived cells (PDLCs) express both osteo/cementogenesis and teno/ligamentogenesis genes. However, an efficient method to induce a tenogenic differentiation of PDLCs has not been thoroughly examined. Therefore, this study tested if growth/differentiation factors (GDFs) enhanced tenogenic characteristics of human PDLCs, as a potential cell source for tendon/ligament engineering. Results demonstrated recombinant GDF-5/GDF-7 inhibited alkaline phosphatase (ALP) activity of PDLCs from passage 3 to 6, while GDF-5 enhanced ALP in dental pulp-derived cells and mesenchymal stem cells. GDF-5 (particularly at 10 ng/ml concentration) induced high expression of both early (scleraxis) and mature (tenomodulin, aggrecan, collagen3) tenogenic genes in P4-6 PDLCs, while inhibiting expression of specific transcription-factors for osteogenic, chondrogenic and adipogenic differentiation. Exogenous GDFs might lead PDLCs being expanded in culture during several passages to highly useful cell source for tendon/ligament engineering.