Microfragmented Fat and Biphasic Calcium Phosphates for Alveolar Cleft Repair: Protocol for a Prospective, Nonblinded, First-in-Human Clinical Study.

BACKGROUND: Biphasic calcium phosphates (BCP) may serve as off-the-shelf alternatives for iliac crest-derived autologous bone in alveolar cleft reconstructions. To add osteoinductivity to the osteoconductive BCPs to achieve similar regenerative capacity as autologous bone, a locally harvested buccal fat pad will be mechanically fractionated to generate microfragmented fat (MFAT), which has been shown to have high regenerative capacity due to high pericyte and mesenchymal stem cell content and a preserved perivascular niche. OBJECTIVE: Our primary objectives will be to assess the feasibility and safety of the BCP-MFAT combination. The secondary objective will be efficacy, which will be evaluated using radiographic imaging and histological and histomorphometric evaluation of biopsies taken 6 months postoperatively, concomitant with dental implant placement. METHODS: Eight patients with alveolar cleft (≥15 years) will be included in this prospective, nonblinded, first-in-human clinical study. MFAT will be prepared intraoperatively from the patient's own buccal fat pad. Regular blood tests and physical examinations will be conducted, and any adverse events (AEs) or serious EAs (SAEs) will be meticulously recorded. Radiographic imaging will be performed prior to surgery and at regular intervals after reconstruction of the alveolar cleft with the BCP-MFAT combination. Biopsies obtained after 6 months with a trephine drill used to prepare the implantation site will be assessed with histological and histomorphometric analyses after methylmethacrylate embedding and sectioning. RESULTS: The primary outcome parameter will be safety after 6 months' follow-up, as monitored closely using possible occurrences of SAEs based on radiographic imaging, blood tests, and physical examinations. For efficacy, radiographic imaging will be used for clinical grading of the bone construct using the Bergland scale. In addition, bone parameters such as bone volume, osteoid volume, graft volume, and number of osteoclasts will be histomorphometrically quantified. Recruitment started in November 2019, and the trial is currently in the follow-up stage. This protocol's current version is 1.0, dated September 15, 2019. CONCLUSIONS: In this first-in-human study, not only safety but also the histologically and radiographically assessed regenerative potential of the BCP-MFAT combination will be evaluated in an alveolar cleft model. When an SAE occurs, it will be concluded that the BCP-MFAT combination is not yet safe in the current setting. Regarding AEs, if they do not occur at a higher frequency than that in patients treated with standard care (autologous bone) or can be resolved by noninvasive conventional methods (eg, with analgesics or antibiotics), the BCP-MFAT combination will be considered safe. In all other cases, the BCP-MFAT combination will not yet be considered safe. TRIAL REGISTRATION: Indonesia Clinical Trial Registry INA-EW74C1N; https://tinyurl.com/28tnrr64. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42371.

Contextualizing sociocultural beliefs about cleft, knowledge of the treatments, and factors associated with delay of treatment in Eastern Indonesia.

INTRODUCTION: Indonesia is a multicultural Asian country with a high incidence of cleft. This study contextualizes how patients' sociocultural backgrounds hinder cleft management in a diverse nation. MATERIAL AND METHODS: This study involved 202 families of cleft patients attending six tertiary care hospitals in South Sulawesi between 2021 and 2022. A mixed-methods, descriptive cross-sectional study employed semi-structured interviews and focus group discussions. Thematic content analysis was done using Murdock's causal attribution of illness. Knowledge of the treatments and surgery expectations used open coding. We held medical team focus group discussions to validate education on treatments. Cleft management education was thematically analyzed based on Indonesia's Minister of Health Decree. RESULTS: Two hundred-two families and ten medical teams participated. Thematic content analysis revealed common beliefs and factors that hinder medical treatments. The participants were 109 Buginese, 57 Makassarese, 16 Durinese, 8 Luwunese, 8 Torajanese, and 4 Mandarese. 22.3 % were unaware of causation, while 29.2 % attributed it to natural causes. About half of the interviewees believed in supernatural attribution. Even though 40 % of participants knew little about the surgery, they agreed that surgery improves appearance and speech. Medical treatments are delayed due to a lack of treatment knowledge, parents' concerns about surgical safety, and beliefs about causes. DISCUSSION: Indigenous societies in South Sulawesi believe in supernatural causes of cleft. Most had incomplete surgical treatment information. An intensive educational health program about causes, treatments, medical specialists, and treatment goals is warranted to enhance patient compliance with medical treatment, ultimately leading to improved health outcomes.

Surgical management of dentigerous cyst arises from ectopic tooth: A report of three consecutive cases and literature review.

BACKGROUND: Dentigerous cysts are slow-growing, asymptomatic lesions that typically form around the crowns of impacted teeth. They are not detected until they start to harm the tissues around the teeth. AIM: The present study aimed to describe surgical techniques for treating dentigerous cysts associated with ectopic teeth. CASES: Three patients with dentigerous cysts associated with ectopic teeth, their surgical approaches, and the supporting literature are presented herein. In two cases, the surgical technique used was intra-oral, and in one case was extra-oral. Under general anesthesia, dentigerous cyst enucleation and ectopic tooth removal were carried out. DISCUSSION: In the present study, the ectopic tooth cases were all linked to dentigerous cysts. Enucleation or marsupialization treatments could be used to treat dentigerous cysts. Enucleation with the removal of the impacted tooth is the preferred treatment for dentigerous cysts. CONCLUSION: To perform minimally invasive surgery, the position of the ectopic teeth, the accessibility of the surgical site, the degree of bone reduction, and the simplicity of instrumentation should all be considered.

Cultural Beliefs on Cleft lip and/or Cleft Palate and Their Implications on Management: A Systematic Review.

OBJECTIVE: This article examines and summarizes the published epidemiological literature on cross-cultural variations. Particular emphasis was put on addressing cross-cultural beliefs on the causes, management, and attitude toward cleft lip and/or cleft palate. A healthcare provider's awareness of these cross-cultural attitudes and beliefs is vital for promoting effective collaboration with patients' families and ensuring a favorable medical outcome. DESIGN: Systematic review. SETTING: Not applicable. PARTICIPANTS: Patients with cleft lip and/or cleft palate, their families, their communities, and healthcare providers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: All relevant and eligible studies were identified using PubMed and Google Scholar databases. The cultural belief was categorized and measured using Murdock's Theories of Illness. The study was reported in compliance with PRISMA guidelines. The quality of the selected studies was evaluated in accordance with the Critical Appraisal Skills Programme criteria (CASP). Fourteen articles covering thirteen countries on four continents met the inclusion criteria. In diverse communities, cleft lip and/or cleft palate was attributed to natural (infection, medication, improper diet, smoke, or radiation) or supernatural (God, eclipse, ancestral spirit, and curse) causes. Reported consequences include stigmatization, inappropriate treatments, leaving patients untreated, and infanticide. CONCLUSION: Cultural beliefs are the main cause of misconceptions surrounding a cleft lip and/or cleft palate. There is also a need for public health care providers' intervention to educate society about the natural causes and ease of management, thereby increasing opportunities for patients substantially.

Anatomical position of the mandibular condyle after open versus closed treatment of unilateral fractures: A three-dimensional analysis.

This study aimed to compare open and closed treatment for unilateral mandibular condyle neck and base fractures by final three-dimensional (3D) condylar position at 6 months follow-up. 3D position was associated with mandibular functioning and pain. A total of 21 patients received open (n = 11) or closed (n = 10) treatment. 3D positions were assessed on cone-beam computed tomography scans. Volume differences, root mean square, translations, and rotations were obtained related to the pursued anatomical position and compared between treatment groups by the Mann-Whitney U test. The 3D position parameters were associated with the maximum interincisal opening (MIO), mixing ability test (MAT), Mandibular Function Impairment Questionnaire (MFIQ), and pain based on Spearman correlation coefficients (rs). Translation in the medial-lateral direction was smaller after open treatment (P = 0.014). 3D position was not associated with the MAT; however, worse position was associated with a smaller MIO. A larger pitch rotation was associated with a worse MFIQ (rs = 0.499, P = 0.025). Volume reduction of the affected condyle was associated with more pain (rs = -0.503, P = 0.020). In conclusion, after unilateral condylar fractures, worse 3D position is associated with a smaller mouth opening and worse patient-reported outcomes. This is independent of the chosen treatment, despite a better anatomical reduction after open treatment.

Applications of CAD/CAM Technology for Craniofacial Implants Placement and Manufacturing of Auricular Prostheses-Systematic Review.

This systematic review was aimed at gathering the clinical and technical applications of CAD/CAM technology for craniofacial implant placement and processing of auricular prostheses based on clinical cases. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, an electronic data search was performed. Human clinical studies utilizing digital planning, designing, and printing systems for craniofacial implant placement and processing of auricular prostheses for prosthetic rehabilitation of auricular defects were included. Following a data search, a total of 36 clinical human studies were included, which were digitally planned and executed through various virtual software to rehabilitate auricular defects. Preoperative data were collected mainly through computed tomography scans (CT scans) (55 cases); meanwhile, the most common laser scanners were the 3dMDface System (3dMD LLC, Atlanta, Georgia, USA) (6 cases) and the 3 Shape scanner (3 Shape, Copenhagen, Denmark) (6 cases). The most common digital design software are Mimics Software (Mimics Innovation Suite, Materialize, Leuven, Belgium) (18 cases), Freeform software (Freeform, NC, USA) (13 cases), and 3 Shape software (3 Shape, Copenhagen, Denmark) (12 cases). Surgical templates were designed and utilized in 35 cases to place 88 craniofacial implants in auricular defect areas. The most common craniofacial implants were Vistafix craniofacial implants (Entific Medical Systems, Goteborg, Sweden) in 22 cases. A surgical navigation system was used to place 20 craniofacial implants in the mastoid bone. Digital applications of CAD/CAM technology include, but are not limited to, study models, mirrored replicas of intact ears, molds, retentive attachments, customized implants, substructures, and silicone prostheses. The included studies demonstrated a predictable clinical outcome, reduced the patient's visits, and completed the prosthetic rehabilitation in reasonable time and at reasonable cost. However, equipment costs and trained technical staff were highlighted as possible limitations to the use of CAD/CAM systems.

A narrative review of the role of Eph receptors in head and neck squamous cell carcinoma.

Tyrosine kinase receptors (TKR) coordinate a variety of pathological processes in head and neck squamous cell carcinoma (HNSCC), and eventually play a role in patient outcomes. In this review, the role of Eph receptors in HNSCC progression and the possibility of targeting these receptors are illustrated. All relevant studies were identified through a comprehensive search of four electronic databases, including PubMed, Scopus, web of science, and Embase till August 2022. EphA2 and EphB4, along with ephrin-B2, were the most extensively studied proteins in this family. However, overexpression of EphB4 and its ligand ephrin-B2 were the only proteins that consistently showed association with a poor outcome, indicating that these proteins might serve as valuable prognostic markers in HNSCC. High expression of EphA3 and EphB4 was found to play a crucial role in radioresistance of HNSCC. EphB4 loss, in particular, was observed to induce an immunosuppression phenotypic HNSCC. Currently, ongoing clinical trials are investigating the benefits of EphB4-ephrin-B2 blockade in combination with standard of care treatment in HNSCC. Further efforts are needed to explore the biological role and behavioral complexity of this family of TKR in HNSCC with great attention to avoid heterogeneity of HNSCC subsites.

A network meta-analysis assessing the effectiveness of various radical and conservative surgical approaches regarding recurrence in treating solid/multicystic ameloblastomas.

Multiple treatment approaches have been undertaken to reduce the incidence of recurrence in solid/multicystic ameloblastoma (SMA), both conservative and radical. A network meta-analysis (NMA) was conducted to assess and compare the effectiveness of these various treatment approaches concurrently. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. PubMed (MEDLINE), ScienceDirect, Scopus, and Web of Science were searched until August 10, 2021. The NMA was conducted using the STATA program. Of 1153 records identified in the search, seven observational studies with 180 patients were included. Six different treatment approaches were identified. Segmental resection ranked highest for reducing the recurrence rate with the highest SUCRA score (77.7), followed by curettage with cryotherapy (66.9) and marginal resection (49.3). Network inconsistencies and publication bias appeared to be absent. According to the Confidence in Network Meta-Analysis (CINeMa) method, the evidence's certainty was low for all comparisons due to imprecision and within-study bias. In conclusion, this study is the first NMA in the field of ameloblastoma. Segmental resection seemed to be the most effective treatment approach for minimizing recurrence in SMA patients. Nevertheless, weak certainty of evidence makes that the results must be regarded with caution.

Stem Cell-Based Tissue Engineering for Cleft Defects: Systematic Review and Meta-Analysis.

This study aimed to analyze the efficacy of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) defects in animal models.Systematic review and meta-analysis.Preclinical studies on alveolar cleft repair in maxillofacial practice.Electronic search was performed using PubMed, Embase, and Cochrane databases. Pre-clinical studies, where stem cell-based tissue engineering was used in the reconstruction of AC and CP in animal models were included. Quality of the selected articles was evaluated using SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation).Review of alveolar cleft bone augmentation interventions in preclinical models.Outcome parameters registered were new bone formation (NBF) and/or bone mineral density (BMD).Thirteen large and twelve small animal studies on AC (21) and CP (4) reconstructions were included. Studies had an unclear-to-high risk of bias. Bone marrow mesenchymal stem cells were the most widely used cell source. Meta-analyses for AC indicated non-significant benefits in favor of: (1) scaffold + cells over scaffold-only (NBF P = .13); and (2) scaffold + cells over empty control (NBF P = .66; BMD P = .31). Interestingly, dog studies using regenerative grafts showed similar to superior bone formation compared to autografts. Meta analysis for the CP group was not possible.AC and CP reconstructions are enhanced by addition of osteogenic cells to biomaterials. Directions and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of bone tissue engineering.

Postoperative Daycare as a Safe and Cost-Effective Option for Secondary Alveolar Bone Graft (SABG) Surgery: A Retrospective Comparative Cohort Study.

OBJECTIVE: To evaluate the outcomes of Secondary Alveolar Bone Grafting (SABG) in patients treated either in daycare or with multiple day hospitalization (MDH) in relation to costs and complication rates. DESIGN: Retrospective comparative cohort study. SETTING: The data was collected from two settings: Postoperative daycare or MDH after oral cleft surgery in an Academic Medical Center in The Netherlands. PATIENTS: Data of 137 patients with unilateral Cleft lip, alveolus, and palate (CLAP) treated between 2006-2018 were evaluated. Registered clinical variables: age, gender, cleft subtype, bone donor site, type of hospitalization, length of stay, additional surgery, complications, surgeons, and costs. INTERVENTIONS: Closure of the alveolar cleft with/without closure of the anterior palate. MAIN OUTCOME MEASURES: Univariate analyses. RESULTS: Of the 137 patients, 46.7% were treated in MDH, and 53.3% in daycare. Total costs for daycare were significantly lower (P < .001). All patients treated in daycare received mandibular symphysis bone, whereas in MDH, 46.9% received iliac crest bone instead. Bone donor site was associated with postoperative care type. Complication rates were slightly but not significantly higher in daycare (26%) vs. MDH (14.1%) (P = .09). Most were Grade I (minor) according to Clavien Dindo classification. CONCLUSIONS: Daycare after alveolar cleft surgery is about as safe as MDH, but significantly cheaper.

Antimicrobial and Pro-Osteogenic Coaxially Electrospun Magnesium Oxide Nanoparticles-Polycaprolactone /Parathyroid Hormone-Polycaprolactone Composite Barrier Membrane for Guided Bone Regeneration.

Introduction: An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process. Methods: In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo. Results: We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (>65%) ranged from 0.40~0.60µm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs. Conclusion: The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.

WEE1 kinase inhibitor MK-1775 sensitizes oral tongue squamous cell carcinoma cells to radiation irrespective of TP53 status.

OBJECTIVE: Oral tongue squamous cell carcinoma (OTSCC) frequently harbors non-functional p53 and depends on G2/M checkpoint mediated by WEE1. WEE1 suppression has been identified as a promising anti-tumor strategy. This study investigated the capacity of WEE1 kinase inhibitor (MK-1775) and its underlying mechanisms in enhancing radiation responses of OTSCC cells in vitro. MATERIALS AND METHODS: WEE1 kinase expression and its downstream target (CDK1) were investigated in OTSCC versus normal oral tissue. A synergistic combination of MK-1775 with radiation on OTSCC cell lines with different p53 statuses was assessed by viability assay. The radio-sensitizing effects of MK-1775 on apoptosis, cell cycle, DNA damage, and mitotic entry were also determined. RESULTS: Irradiation enhanced CDK1 expression in all tested cell lines, though the effect was far more pronounced in p53 mutated cell lines. MK-1775 exhibited inhibitory effects against the survival of all cell lines and enhanced their response to the radiation. These effects were strongly elicited by induction of apoptosis and lethal mitosis, but less likely by abrogation of radiation-induced G2 arrest. CONCLUSION: These results demonstrate the efficacy of MK-1775 in enhancing the radiation effect on OTSCC in vitro associated with a significant apoptotic death rate, identifying WEE1 inhibitor as a potent radiosensitizer in OTSCC irrespective of p53 mutational status.

The epidemiology and management of odontomas: a European multicenter study.

INTRODUCTION: Odontoma is the most commonly diagnosed odontogenic tumor of the oral cavity. The objective of the present study was to assess the demographic variables, patterns, diagnostic features, and management issues of odontomas treated at several European departments of maxillofacial and oral surgery. MATERIALS AND METHODS: This study was conducted at 8 European departments of oral surgery between January 1, 2004, and December 31, 2018. Only patients with odontomas were included. The following data were recorded for each patient: gender, age, comorbidities, site, size of odontomas, radiographic features, type of odontoma, treatment of odontomas, treatment of associated teeth, complications, and recurrence. RESULTS: A total of 127 patients (70 male and 57 female patients) with odontomas were included. The mean age was 22 years; 71 odontomas were found in the mandible, whereas 56 in the maxilla. In the mandible, the most frequently involved subsite was the parasymphysis, while in the maxilla, the most common subsite was the upper incisor region. The mean size of included odontomas was 15.3 mm. On the whole, 62 complex odontomas, 50 compound odontomas, and 15 mixed-type odontomas were observed. Complete excision of the odontomas was performed in 121 patients. In 24 patients, the extraction of deciduous teeth was performed, and in 43 patients, one or more permanent teeth were removed. Finally, in 9 patients, a partial excision of the odontoma was performed. Recurrence was observed in 4 cases out of 127 patients. CONCLUSIONS: Dental practitioners should be aware of the distinct clinical and radiographic features of odontoma in order to perform an appropriate and early diagnosis. Conventional radiography, such as panoramic radiograph, is often sufficient technique for a diagnosis after clinical suspicion or for an incidental diagnosis to prevent later complications, such as impaction or failure of eruption of teeth.

Oral functioning after open versus closed treatment of unilateral condylar neck or base fractures: A two-centre controlled clinical trial.

BACKGROUND: Oral functioning and rehabilitation in patients after condylar trauma can be measured by objective functional outcomes and patient-reported outcomes. The similarities or differences between these outcomes may contribute to the decision if open treatment (OT) or closed treatment (CT) will obtain the most advantageous results. OBJECTIVES: The aim of this study was to compare OT versus CT for unilateral condylar mandibular neck or base fractures in a two-centre controlled clinical trial by objective functional outcomes and patient-reported outcomes measured at 6 weeks and 6 months follow-up. Additionally, these outcomes were compared within each group. METHODS: Patients were enrolled between January 2017 and November 2019. In one centre, patients received OT by extra-oral open reduction and internal fixation. In another centre, patients received CT by maxillomandibular fixation. Objective measurements included the mixing ability test (MAT) and mandibular active range of motion (ROM). Patient-reported outcomes included the mandibular function impairment questionnaire (MFIQ) and visual analogue scale (VAS) for pain. Independent t-tests and Mann-Whitney U-tests were used to determine differences between the treatment groups at 6 weeks and 6 months follow-up. Paired t-tests and Wilcoxon signed rank tests were used to determine differences within each group. RESULTS: Thirty-three patients were enrolled. No differences were found between the groups treated with OT or CT for MAT, ROM, MFIQ and VAS. Both groups showed functional improvement. CONCLUSION: Good objective functional outcomes and patient-reported outcomes were achieved with both OT and CT in patients with unilateral condylar mandibular neck or base fractures.

Radiation modulates expression and related activities of c-Met protein in oral tongue squamous cell carcinoma cell lines.

OBJECTIVES: c-Met, a receptor tyrosine kinase, is involved in the growth, invasion and metastasis of a variety of cancers. In a set of cell lines from several solid tumors, a five-fold increase in c-Met expression after irradiation has been reported. This study aimed to assess if c-Met is likewise abundantly expressed in oral tongue squamous cell carcinoma (OTSCC) upon exposure to irradiation, followed by a Met-induced biological response. MATERIALS AND METHODS: Six OTSCC cell lines were exposed to gamma radiation doses of 2, 4, and 6 Gray. The changes in c-Met protein levels were assessed by western blot and flow cytometry. c-Met gene expression, cell migration, proliferation and cell cycle assays were performed as phenotypic readouts. RESULTS: Irradiation resulted in upregulation of c.Met in all cell lines with different time kinetics. On average the cells displayed minimal c-Met expression on their surface ranging from 5 to 30% of total protein. Abrupt downregulation of c-Met surface expression occurred one hour after radiation but recovered 48 h post-radiation. Intracellularly, the highest level of expression was found on day 5 after radiation exposure. Irradiation induced aggressive invasive potential of the cells as determined in cell migration assays, particularly in cell lines with the highest c-Met expression. CONCLUSIONS: These results provide novel insights into both intracellular and extracellular dynamics of c-Met expression profiles upon irradiation of OTSCC cells in vitro. It might also suggest that radiation enhances cell migration, indicative of invasiveness, through c-Met up-regulation, at least for certain types of OTSCC cells.

Unusual generalized tetanus evolving from odontogenic infection: A case report and review of recent literature.

Tetanus is an acute and vaccine-preventable disease caused by anaerobic bacteria, Clostridium tetani. This bacterium can enter the human body via a deep wound, burn injury or medical procedure; however, certain cases also originate from odontogenic infection. In the present study, a tetanus infection associated with dental origin in a 44-year-old man is reported. The case was complicated by lockjaw and difficulty swallowing that worsened over a few days, followed by a generalized spasm. Furthermore, a literature review was performed, in which six reported cases of tetanus, presumed to be of dental or oral origin, were identified between 2011and 2021. General practitioners, especially dentists, should be aware of tetanus associated with odontogenic origin even without a history of an external penetrating wound or other medical procedures:.

Influence of patient-related factors on intraoperative blood loss during double opposing Z-plasty Furlow palatoplasty and buccal fat pad coverage: A prospective study.

Background: Surgical procedures including palatoplasty have a risk for complications. The aim of this study was to investigate the intraoperative and early postoperative blood loss using the buccal fat pad (BFP) during cleft lip and/or cleft palate (CL/P) surgery. Material and Methods: This prospective study included a total of 109 patients with cleft palate (CP) during a three-month period of treatment at Hasanuddin University Dental Hospital (permanent center) and charity trips in rural parts of Eastern Indonesia. All patients were treated with DOZ Furlow technique combined with BFP graft. Before and after surgery, the total amount of intraoperative blood loss was calculated by measuring the weight differences of the gauze swabs that were used to control the surgical bleeding followed by a complete blood count at three days postoperatively. Results: The difference in the amount of blood loss based on age categories in charity groups was found to be significant (P<0.05). Overall, we found that high body weight and operation time significantly contributed to increased blood loss (P<0.05). Conclusions: Weight and operative time can contribute to more blood loss during palatoplasty. Key words:Buccal fat pad, complication, cleft lip, cleft palate, palatoplasty.

Significance of immunohistochemistry biomarkers in prediction of malignant transformation of oral lichen planus: A systematic review

Background: Oral lichen planus (OLP) is a chronic inflammatory disorder with increased risk for malignanttransformation. Biomarker validation is a pivotal step in moving newly discovered biomarkers towards clinicalimplementation. We performed a systematic review of studies on biomarkers related to OLP, wherein biomarkershave been described in at least two independent studies. Our aim was to determine whether any of these biomarkers might be promising in predicting the increased risk of malignant transformation of OLP.Material and Methods: We searched the following databases until August 2021: PUBMED, EMBASE, and Web ofScience. Due to high heterogeneity, a qualitative rather than quantitative assessment was conducted. Only proteinsthat consistently showed a significantly high level of expression in neoplastic tissues versus OLP in two or morepublications were considered as promising markers.Results: Initial database researches identified 1671, of which 24 articles were included in the final analysis. Themost frequently reported proteins were p53, Bcl-2 and Ki-67, though there were controversies. PCNA and P21were the only proteins that showed consistent evidence of clinical usefulness as cancer predictors to be consideredas promising markers. Extensive methodological variations in the evaluation of expressions and statistical analyses of the included markers were observed, which hampered comparisons of the results. Conclusions: Multiple levels of heterogeneity with a scarcity of high-quality studies were identified. PCNA and P21were identified as promising predictive markers for evaluating the risk of malignant transformation of OLP, but theyrequire further validation. The focus of future research on validation of predictive biomarkers of OLP should be considered as a high priority because it will accelerate the introduction of newly discovered markers into the clinical setting. (AU)

Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2.

The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the in-vivo osteoinductive efficacy in a subcutaneous bone induction model in rats. In-vitro characterization data showed that the BpNcCaP + BMP-2 granules were comprised of hexagonal hydroxyapatite with an average crystallite size ranging from 19.7 to 25.1 nm and a grain size at 84.13 ± 28.46 nm. The vickers hardness of BpNcCaP was 32.50 ± 3.58 HV 0.025. BpNcCaP showed no obvious cytotoxicity and was favorable for the adhesion of pre-osteoblasts. BMP-2 incorporation rate could be as high as 65.04 ± 6.01%. In-vivo histomorphometric analysis showed that the volume of new bone induced by BpNcCaP exhibited a BMP-2 amount-dependent increasing manner. The BpNcCaP+50 µg BMP-2 exhibited significantly more degradation and fewer foreign body giant cells in comparison with BpNcCaP. These data suggested a promising application potential of BpNcCaP + BMP-2 in repairing LVBDs.