Sinus augmentation with poly(ε)caprolactone-ß tricalcium phosphate scaffolds, mesenchymal stem cells and platelet rich plasma for one-stage dental implantation in minipigs.

PURPOSE: This study evaluated the efficacy of a tube-shaped poly(ε) caprolactone - ß tricalcium phosphate (PCL-TCP) scaffold with the incorporation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and platelet-rich plasma (PRP) for bone regeneration in the procedure of single-stage sinus augmentation and dental implantation in minipigs. METHODS: Implants were placed in the bilateral sides of the maxillary sinuses of 5 minipigs and allocated to a PCL-TCP+hUCMSCs+PRP group (n=5), a PCL-TCP+PRP group (n=5), and a PCL-TCP-only group (n=6). After 12 weeks, bone regeneration was evaluated with soft X-rays, micro-computed tomography, fluorescence microscopy, and histomorphometric analysis. RESULTS: Four implants failed (2 each in the PCL-TCP+hUCMSCs+PRP and PCL-TCP+hUCMSC groups). An analysis of the grayscale levels and bone-implant contact ratio showed significantly higher mean values in the PCL-TCP+hUCMSCs+PRP than in the PCL-TCP group (P=0.045 and P=0.016, respectively). In fluoromicroscopic images, new bone formation around the outer surfaces of the scaffolds was observed in the PCL-TCP+hUCMSCs+PRP group, suggesting a tenting effect of the specially designed scaffolds. Bone regeneration at the scaffold-implant interfaces was observed in all 3 groups. CONCLUSIONS: Using a tube-shaped, honeycombed PCL-TCP scaffold with hUCMSCs and PRP may serve to enhance bone formation and dental implants' osseointegration in the procedure of simultaneous sinus lifting and dental implantation.

Drug Therapeutics Delivery to the Salivary Glands: Intraglandular and Intraductal Injections.

Salivary gland hypofunction and xerostomia following pathological conditions like Sjogren's syndrome or head and neck radiotherapy usually lead to tremendous impairment of oral health, speech, and swallowing. The use of systemic drugs to alleviate the symptoms of these conditions has been associated with various adverse effects. Techniques of local drug delivery to the salivary gland have grown enormously to address this problem properly. The techniques include intraglandular and intraductal injections. In this chapter, we will provide a review of the literature for both techniques while incorporating our lab experience in using them.

Mesenchymal stem cells and platelet-rich plasma-impregnated polycaprolactone-ß tricalcium phosphate bio-scaffold enhanced bone regeneration around dental implants.

BACKGROUND: Finding a material that supports bone regeneration is the concern for many investigators. We supposed that a composite scaffold of poly(ε) caprolactone and ß-tricalcium phosphate (PCL-TCP) would entail desirable characteristics of biocompatibility, bioresorbability, rigidity, and osteoconductivity for a proper guided bone regeneration. Furthermore, the incorporation of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) would boost the bone regeneration. We conducted this study to evaluate the bone regeneration capacity of PCL-TCP scaffold that is loaded with MSCs and PRP. MATERIALS AND METHODS: Five miniature pigs received 6 implants in 6 created-mandibular bony defects in the right and left lower premolar areas. The bony defects were managed according to the following three groups: the PCL-TCP scaffold loaded with MSCs and PRP (MSCs+PRP+PCL-TCP) group (n = 10), PCL-TCP scaffold loaded with PRP (PRP+PCL-TCP) group (n = 10), and PCL-TCP scaffold group (n = 10). After 12 weeks, the bone regeneration was assessed using fluorochrome bone labeling, µCT bone morphogenic analysis, and histomorphometric analysis. RESULTS: All of the three groups supported the bone regeneration around the dental implants. However, the PCL-TCP scaffold loaded with MSCs and PRP (MSCs+PRP+PCL-TCP) group showed non-significant higher bone surface, bone specific surface, and bone surface density than the other two groups as revealed by the µCT bone morphogenic analysis. Histologically, the same group revealed higher bone-implant contact ratio (BIC) (p = 0.017) and new bone height formation (NBH, mm) (p = 0.0097) with statistically significant difference compared to the PCL-TCP scaffold group. CONCLUSIONS: PCL-TCP scaffold is compatible for bone regeneration in bone defects surrounding dental implants. Moreover, the incorporation of MSCs and PRP optimized the bone regeneration process with respect to the rate of scaffold replacement, the height of the regenerated bone, and implant stability.

Factors Affecting Functional Sensory Recovery After Inferior Alveolar Nerve Repair Using the Nerve Sliding Technique.

PURPOSE: The nerve sliding technique (NST) was introduced for repairing inferior alveolar nerve (IAN) defect and overcoming the disadvantages of conventional surgical treatment methods such as nerve graft. This study was conducted to identify factors associated with functional sensory recovery (FSR) following inferior alveolar nerve repair using the NST. PATIENTS AND METHODS: This was a retrospective cohort study including all patients who underwent IAN repair using the NST at Seoul National University Dental Hospital, Department of Oral and Maxillofacial Surgery from February 2009 to March 2020. The damaged part of the IAN was excised, and the incisive branch was transected intentionally to perform direct anastomosis without tension. Cox proportional hazard analysis was utilized to determine the relationships between predictor variables (age, gender, chief complaints, preoperative sensory results, duration from injury to repair, length of nerve tissue resected during the procedure, and neuroma formation) and outcome variable (time to FSR). RESULTS: The sample was composed of 16 patients with a mean age of 56.1 ± 10.1 years, 25% were males and 75% were females. The mean nerve gap deficit was 7.69 mm (3-15 mm). Ten patients (62.5%) achieved FSR with a median time from operative treatment to FSR of 84.5 days. Dental implant placement was found as the main cause for IAN injury (93.8%) and 56.2% of patients complained of hypoesthesia and dysesthesia. Factors associated with time to FSR at 1 year were age, chief complaint, and early repair. Younger patients (P = .041) and patients without dysesthesia (P = .019) were more likely to achieve FSR. Higher proportion of early repair group achieved FSR, although not statistically significant (P = .068). CONCLUSIONS: The use of NST in repair of IAN defects up to 15 mm achieved 62.5% FSR. Younger age and absence of dysesthesia were associated with higher FSR.

Tissue Engineering of Oral Mucosa and Salivary Gland: Disease Modeling and Clinical Applications.

Oral mucosa and salivary gland are composed of complex and dynamic networks of extracellular matrix, multiple cell types, vasculature, and various biochemical agents. Two-dimensional (2D) cell culture is commonly used in testing new drugs and experimental therapies. However, 2D cell culture cannot fully replicate the architecture, physiological, and pathological microenvironment of living human oral mucosa and salivary glands. Recent microengineering techniques offer state of the science cell culture models that can recapitulate human organ structures and functions. This narrative review describes emerging in vitro models of oral and salivary gland tissue such as 3D cell culture models, spheroid and organoid models, tissue-on-a-chip, and functional decellularized scaffolds. Clinical applications of these models are also discussed in this review.

Effects of Chewing Exerciser on the Recovery of Masticatory Function Recovery after Orthognathic Surgery: A Single-Center Randomized Clinical Trial, a Preliminary Study.

Background and Objectives: The aim of this study was to evaluate the effects of the chewing exerciser (CE) on the functional recovery of the masticatory muscles after orthognathic surgery. Material and Methods: This randomized clinical trial was conducted in patients undergoing bimaxillary orthognathic surgery including bilateral sagittal split ramus osteotomy. Postoperative physiotherapy (PT) was performed for 3 weeks starting 3 weeks after the surgery. The patients were randomly divided into two groups: control (Con) (conventional PT) group and CE group (use of CE in addition to conventional PT). The masticatory function was evaluated based on three standards: bite force (BF), amount of mouth opening (MO), and surface electromyography (sEMG) of the anterior temporal muscle (TA), masseter muscle (MM), sternocleidomastoid muscle, and anterior belly of digastric muscle before, 3 weeks (before PT) and 6 weeks after the surgery (after PT). Results: Finally, 22 subjects participated in this study: 10 patients for Con group and 12 patients for CE group. In both groups, the BF, which was reduced significantly after the surgery, recovered after the PT similar to that before the surgery. In both groups, the MO was also significantly reduced by the surgery. However, it did not recover as much, as it was before the surgery after applying the PT. There was no difference in BF and MO between the two groups. All muscles did not show significant changes in sEMG by surgery and PT at both resting and clenching states. Conclusion: Applying CE as a PT after orthognathic surgery did not cause any harmful side effects. In both groups, the weakened muscle activity after orthognathic surgery (OGS) was adequately restored 6 weeks after the surgery. However, CE did not offer a statistically significant benefit to the masticatory function in the recovery process after OGS.

Leiomyosarcoma of the jaw: case series.

OBJECTIVES: Leiomyosarcoma is a malignant neoplasm that affects smooth muscle tissue and it is very rare in the field of oral and maxillofcial surgery. The purpose of this study was to obtain information on diagnosis of and treatment methods for leiomyosarcoma by retrospectively reviewing of the cases. PATIENTS AND METHODS: The study included nine patients who were diagnosed with leiomyosarcoma in the Department of Oral and Maxillofacial Surgery at Seoul National University Dental Hospital. The subjects were analyzed with respect to sex, age, clinical features, primary site of disease, treatment method, recurrence, and metastasis. RESULTS: Particular clinical features included pain, edema, mouth-opening limitations, dysesthesia, and enlarged lymph nodes. All cases except one were surgically treated, and recurrence was found in two cases. Four of nine patients were followed up without recurrence and one patient underwent additional surgery due to recurrence. CONCLUSION: In our case series, notable symptoms included pain, edema, mouth-opening limitations, and dysesthesia; however, it was difficult to label these as specific symptoms of leiomyosarcoma. Considering the aggressive characteristics of the disease and poor prognosis, surgical treatment is necessary with careful consideration of postoperative radiotherapy and chemotherapy.

FK506 immunosuppression for submandibular salivary gland allotransplantation in rabbit.

Objectives: We compared the outcomes of two different doses of FK506 (tacrolimus) for immunosuppression in submandibular salivary gland (SMG) allotransplantation. Materials and Methods: Three SMG allotransplantation groups were established (n=6 per group) as follows: allograft rejection control (Allo-Ctrl), low dose (0.08 mg/kg) of FK506 (FK506-L), and high dose (0.16 mg/kg) of FK506 (FK506-H). Allograft survival and rejection were assessed by clinical observation, interleukin-2 levels as determined by enzyme-linked immunosorbent assay, blood sampling for complete blood count (CBC), and histological evaluation. Results: Body weight and anorexia were higher in the FK506-H group but without a significant difference compared with the FK506-L population. CBC revealed a non-significantly reduced number of changes in the FK506-L group. Four glands in the FK506-H group and two glands in the FK506-L group were viable and functioning post-transplantation. Conclusion: The survival rate of allotransplanted glands was higher in conjunction with the high dose of 0.16 mg/kg of FK506, with no major difference in the side-effect profile when compared with the low dose of 0.08 mg/kg short-term outcomes.

Tantalum - Poly (L-lactic acid) nerve conduit for peripheral nerve regeneration.

Recently, Tantalum (Ta) has been re-explored and used with bone implants to promote bone regeneration. It has previously been extensively used as a nerve suture material; however, its use was abandoned because of the formation of scar tissue. In this study, we constructed a nerve conduit made of poly (L-lactic acid) PLA (outer layer) and tantalum Ta (inner layer) to evaluate its efficiency in the promotion of peripheral nerve regeneration. MATERIALS AND METHODS: First, we conducted an in vitro study to evaluate the viability and proliferation of Schwann cells and rat pheocromocytoma (PC-12) cells on Ta-PLA sheets using Enhanced Cell Viability Assay Kit (EZ-CYTOX). An in vivo study was then performed using Sprague Dawley rats that were randomly divided into the following three groups: sham, PLA, and Ta-PLA nerve conduits. The nerve conduit was placed over a 10-mm gap of the rat sciatic nerve to promote nerve regeneration. The rats were observed over 12 wk with weekly sciatic functional index functional assessment. At the end of 12 wk, the nerve regeneration outcome was assessed through dorsal root ganglions (DRG) retrograde neurons labeling, histomorphometric analysis, and histological analysis. RESULTS: The in vitro study showed significant viability and proliferation of Schwann cells in the Ta-PLA group than in the other groups. In the in vivo study, the gross findings revealed well-regenerated neural tissue in both the experimental groups with no scarring. The histological analysis showed that about 50 % of the conduits were filled with axons with a higher tendency for peripheral growth in the PLA group than for central growth within the Ta-PLA group conduits. The retrograde labeled neurons were significantly higher in Ta-PLA group than in the PLA group. Ta-PLA showed non-significant difference in the total fibers compared to the sham group. CONCLUSION: Tantalum proved favorable for the growth of Schwann cells.In vivo, Ta-PLA nerve conduit induced peripheral nerve regeneration without scar tissue formation.

Fracture of Standard Titanium Mandibular Reconstruction Plates and Preliminary Study of Three-Dimensional Printed Reconstruction Plates.

PURPOSE: A cohort review was performed to compare the effect of a number of variables on mandible reconstruction plate (R-plate) survival and to identify the potential risk factors for plate fracture. We also reported our preliminary results of 3-dimensional (3D) printed reconstruction plates. PATIENTS AND METHODS: The data from patients who had undergone mandibular reconstruction using reconstruction plates were evaluated for age, gender, mandibular resection indication, defect site and length, remaining occluded teeth, reconstruction plate type, simultaneous soft or bone tissue reconstruction, and radiotherapy. The plate survival rate was estimated using the Kaplan-Meier curve, and the variables were compared using the log-rank (Mantel-Cox) test. Multifactorial risk correlation was determined using logistic regression analysis. RESULTS: The study included 159 patients who had been followed for 97 ± 5.4 months. Of the 159 patients, 22 had experienced plate fracture that had occurred within 20 months. Most of the plate fractures had occurred near the mandibular bone stump, passing through the shoulder of the plate hole or the bridge between the subsequent plate holes. The overall survival was 86.2%. Patients with few occluded teeth (type I) had a significantly greater R-plate survival rate compared with those with many occluded teeth (P = .045). Laterocentral "LC" defects had a significantly lower survival rate (44.4%) compared with lateral "L" defects (84.5%; P = .00). The survival rates with soft tissue (88.7%) or bone tissue reconstruction (100%) were significantly different compared with that for R-plate alone (40%; P = .000 and P = .004, respectively). Four patients received 3D printed R-plates and were followed for 2 to 8 months (mean, 4 months) with no complications. CONCLUSIONS: Patients with many remaining occluded teeth, LC defect, and the absence of simultaneous soft or bone tissue reconstruction were associated with a lower plate survival rate. Bending of the plate increased the incidence of plate fracture, and the use of 3D printed customized R-plates seems a valuable alternative.

Chondrosarcoma of the jaw: a retrospective series.

OBJECTIVES: Low-grade chondrosarcoma presents with features similar to those of benign lesions, such as chondroma and synovial chondromatosis, increasing the difficulty in reaching an accurate diagnosis preoperatively. In this study, we retrospectively reviewed 10 chondrosarcoma cases and evaluated the diagnostic approaches and management modalities. STUDY DESIGN: Ten cases were included in the present study. We evaluated the clinical features, initial diagnosis, histopathology subtype, immunohistologic markers, final diagnosis, and treatment modalities. RESULTS: Most of the lesions were found in the mandible. Two cases were followed up for 1 month and 4 years, respectively as benign lesions before malignant changes were detected. With regard to chondrosarcoma histopathology subtypes, 6 cases were identified as conventional chondrosarcoma, whereas 4 cases were diagnosed as mesenchymal chondrosarcoma with aggressive behavior; of these, 3 were associated with local recurrence and metastasis. The immunohistologic markers showed no specificity for chondrosarcoma. CONCLUSIONS: Distinguishing low-grade chondrosarcoma, particularly in the temporomandibular joint, from benign lesions, such as chondroma or synovial chondromatosis, remains difficult. Currently, the correlation between clinical, radiographic, and histologic features accompanied by close follow-up is extremely important for patients diagnosed with chondrogenic lesions. Postoperative radiotherapy seems to be beneficial in patients with positive surgical margins.

Mesenchymal Stem Cell Therapy in Submandibular Salivary Gland Allotransplantation: Experimental Study.

BACKGROUND: Allotransplantation of submandibular salivary glands (SMGs) could be an alternative treatment option for severe keratoconjunctivitis sicca in noncandidates for autologous SMG transplantation. This study was conducted to evaluate the effect of allogeneic mesenchymal stem cell (MSC) therapy on the survival of allotransplanted SMGs. METHODS: Thirty-six SMG allotransplantations (n = 6 per group) were performed in New Zealand white rabbits and randomly divided into the following groups: allograft control (Allo-Ctrl), low-dose FK506 (FK506-L), high-dose FK506 (FK506-H), allogeneic MSCs, MSCs+FK506-L, and MSCs+FK506-H. Rabbits were closely observed for 2 weeks. Gland viability and rejection were assessed by monitoring interleukin-2 levels by ELISA, sialoscintigraphy, M3-muscarinic acetylcholine receptor expression, histological evaluation, and apoptosis assay. RESULTS: Intraoperatively, all glands showed patency and saliva flow except 1 gland. Sialoscintigraphy revealed significantly higher saliva production within the MSC-treated glands. Histologically, MSC-treated glands showed higher glandular tissue preservation and less acini atrophy. The MSCs+FK506-H group revealed significantly lower apoptosis percentage. The highest survival was observed in the MSCs+FK506-H group, followed by the FK506-H and MSCs+FK506-L groups, and lastly less in the FK506-L and MSCs groups. CONCLUSIONS: Concurrent administration of MSCs with FK506-H (0.16 mg/kg) resulted in higher survival rate with greater glandular tissue preservation and salivary secretion. MSCs with FK506-L (0.08 mg/kg) could be an alternative to FK506-H (0.16 mg/kg) in salivary gland allotransplantation.

Per-oral cross-facial sural nerve graft for facial reanimation.

BACKGROUND: Cross-facial nerve graft is considered the treatment of choice for facial reanimation in patients with unilateral facial palsy caused by central facial nerve damage. In most cases, a traditional parotidectomy skin incision is used to locate the buccal and zygomatic branches of the facial nerve. METHODS: In this study, cross-facial nerve graft with the sural nerve was planned for three patients with facial palsy through an intraoral approach. RESULTS: An incision was made on the buccal cheek mucosa, and the dissection was performed to locate the buccal branch of the facial nerve. The parotid papillae and parotid duct were used as anatomic landmarks to locate the buccal branch. CONCLUSIONS: The intraoral approach is more advantageous than the conventional extraoral approach because of clear anatomic marker (parotid papilla), invisible postoperative scar, reduced tissue damage from dissection, and reduced operating time.