This patient series reports the outcomes of CAD/CAM prosthetic reconstructions in patients with cleft lip and palate (n = 9, aged 27 to 76) who have experienced significant failure with conventional restorative and fixed prosthodontic treatments. The objective of the protocol is to establish a functional and patient-friendly prosthetic structure for individuals with unilateral/bilateral cleft lip and palate (UCLP/BCLP) while minimising the requirement for specialised follow-up care in the cleft unit. The study data were obtained from a retrospective cohort at Helsinki University Hospital. Prosthetic reconstructions were performed using CAD/CAM bar structures by the Atlantis 2in1 system or Createch removable telescope structures, supported by four to eight maxillary dental implants. Out of the nine patients, seven experienced no complications. One prosthesis fracture occurred after 16 months due to a design error in the original framework, and one patient experienced failure of osseointegration in a dental fixture (specifically, one fixture out of the eight maxillary implants in this patient). In total, 56 implants were successfully placed. The maxillary dentition of elderly patients with cleft lip and palate often poses challenges due to periodontal and reconstructive issues. An implant-supported CAD/CAM bar with a removable telescope suprastructure offers an easily maintained and functional solution for dental rehabilitation.

UNASSIGNED: Clefts of the lip, alveolus and/or palate (CLA/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic/genetic causes is important for personalized tailored care, identification of (unrecognized) comorbidities, and accurate genetic counseling. Therefore, next generation sequencing (NGS)-based targeted gene panel testing is increasingly implemented in diagnostics of CLA/P patients. In this retrospective study, we assess the yield of NGS gene panel testing in a cohort of CLA/P cases.
UNASSIGNED: Whole exome sequencing (WES) followed by variant detection and interpretation in an a priori selected set of genes associated with CLA/P phenotypes was performed in 212 unrelated CLA/P patients after genetic counseling between 2015 and 2020. Medical records including family history and results of additional genetic tests were evaluated.
UNASSIGNED: In 24 CLA/P cases (11.3%), a pathogenic genetic variant was identified. Twenty out of these 24 had a genetic syndrome requiring specific monitoring and follow-up. Six of these 24 cases (25%) were presumed to be isolated CLA/P cases prior to testing, corresponding to 2.8% of the total cohort. In eight CLA/P cases (3.8%) without a diagnosis after NGS-based gene panel testing, a molecular diagnosis was established by additional genetic analyses (e.g., SNP array, single gene testing, trio WES).
UNASSIGNED: This study illustrates NGS-based gene panel testing is a powerful diagnostic tool in the diagnostic workup of CLA/P patients. Also, in apparently isolated cases and non-familial cases, a genetic diagnosis can be identified. Early diagnosis facilitates personalized care for patients and accurate genetic counseling of their families.

Although childhood obesity matters, the association between body mass index (BMI) and bone mineral density (BMD) progression in grafted tissue after secondary alveolar bone grafting (ABG) for children with cleft alveolus is scarcely studied. Accordingly, this study explored the influence of BMI on BMD progression after ABG.
In total, 39 patients with cleft alveolus receiving ABG at the mixed dentition stage were enrolled. Patients were classified as underweight, normal weight, or overweight or obese according to age- and sex-adjusted BMI. BMD was measured in Hounsfield units (HU) from cone-beam computed tomography scans obtained 6 months (T1) and 2 years (T2) postoperatively. Adjusted BMD (HUgrafted tissue/HUpogonion, BMDa) was used for further analysis.
For underweight, normal-weight, and overweight or obese patients, BMDaT1 values were 72.87%, 91.85%, and 92.89%, respectively (p = 0.727); BMDaT2 values were 111.49%, 112.57%, and 113.10% (p = 0.828); and density enhancement rates were 29.24%, 24.61%, and 22.14% (p = 0.936). No significant correlation was observed between BMI and BMDaT1, BMDaT2, or density enhancement rates (p = 0.223, 0.156, and 0.972, respectively). For patients with BMI < 17 and ≥ 17 kg/m2, BMDaT1 values were 89.80% and 92.89%, respectively (p = 0.496); BMDaT2 values were 111.49% and 113.10% (p = 0.216); and density enhancement rates were 23.06% and 26.39% (p = 0.573).
Patients with different BMI values had similar outcomes (BMDaT1, BMDaT2, or density enhancement rate) after our ABG procedure in the 2-year postoperative follow-up.

An alveolar cleft is the most common congenital bone defect. This systematic review aimed to investigate the use of stem cells for alveolar cleft repair and summarize the outcomes of clinical research studies. The electronic databases PubMed, Scopus, Web of Sciences, and Google Scholar were utilized to search the literature for relevant studies after administering specific inclusion and exclusion criteria. The search included articles that were published from 2011 to 2021 and specific keywords were used in the databases. The search was completed by two independent reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Only four studies satisfied both the inclusion and exclusion criteria and were included in this systematic review. These studies investigated different aspects of bone reconstruction in the maxillary alveolar bone by stem cells, including cell types, clinical applications, biomaterial scaffolds, and follow-up period. The accumulated evidence in this systematic review is limited and insufficient to support the role of stem cell use in bone regeneration of maxillary alveolar bone defects. The outcome of using stem cells was studied only in 57 subjects from the four included studies. Although the noninvasive methods of isolating stem cells make them attractive resources for bone regeneration, more research is required in order to standardize and investigate stem cell therapy. This should be done beforehand in adults in less invasive procedures such as bone defect repair in dentistry prior to considering this type of therapy in this vulnerable patient population.

OBJECTIVE: This single-centre retrospective cohort study aimed to evaluate secondary alveolar bone grafting (SABG) and identify the factors associated with failure.
METHODS: Individuals born with alveolar cleft with or without cleft palate who had SABG consecutively between 2004-2006 and 2011-2013 were enrolled in this study. After the exclusion of 20 cases due to poor quality radiographs, 115 patients (50 girls and 65 boys) who had undergone 131 SABG procedures were included. According to a modification of the Bergland Scale (mBS), the alveolar bone level was assessed using occlusal films obtained 3 months after SABG. Data on factors plausible for SABG failure were collected from patient records, photographs, cast models, and presurgical occlusal radiographs. The Mantel Haenszel Chi-Square test was used to test the possible impact of these factors on the mBS scores.
RESULTS: A total failure (mBS score of 4) was observed in 9% of the cases. The alveolar bone level correlated with cleft laterality (P = 0.039), alveolar cleft extension (P = 0.033), age at SABG (P = 0.007), root developmental stage (P = 0.021), and oral hygiene (P = 0.007).
CONCLUSIONS: Secondary alveolar bone grafting failure was correlated with a bilateral alveolar cleft, absence of an initial partial alveolar bridge, higher age, increased root developmental stage, and poor oral hygiene. Efforts to achieve optimal oral hygiene are recommended to improve outcomes, particularly when SABG is performed in individuals with a bilateral cleft, increased alveolar cleft extension, or at higher ages.

BACKGROUND: An alveolar cleft commonly affects 75% of cleft lip and palate patients. While it is common practice to provide a course of orthodontic treatment before alveolar bone grafting, there are no previous high-quality studies reporting on the benefits of this type of treatment.
OBJECTIVE: The aim of the study is to evaluate the effectiveness of pre-alveolar bone graft orthodontics for unilateral non-syndromic cleft palate patients.
METHODS: The PABO trial is a multicentric, parallel, two-arm, single-blinded randomised controlled trial. The inclusion criteria include unilateral cleft alveolus patients requiring bone graft and between the age group of 8 and 13 years with erupted upper central incisors. Participants will be recruited at three centres across India. Participants will be randomised to orthodontic treatment or no orthodontic treatment group. Both groups of participants will have alveolar bone graft surgery and will be followed up for 6 months after surgery. The primary outcome will be the success of the alveolar bone graft measured by anterior oblique radiograph and secondary outcomes include quality of life, cost analysis and quality of the dento-occlusal outcome. Data analysis will be carried out by an independent statistician at the end of the study.
CONCLUSIONS: This study is the first to evaluate the effect of orthodontics on alveolar bone graft success. The increased burden of care for these patients with multiple treatments required from multiple specialists from birth to adult life highlights the need for reducing unnecessary treatment provision.
BACKGROUND: Clinical Trials Registry - India, CTRI/2020/10/028756 . Trial prospectively registered on 29 October 2020. .

The alveolar cleft is a bone-related developmental defect in the alveolar process of the maxillae, which is termed as cleft alveolus. The deformity occurs in 75% of the cleft palate and lip patients. Reconstructive surgery can provide both functional and esthetic benefits to such individuals. Conflicting opinions exist on the management of alveolar cleft, and these affect the treatment planning. We present the case of a 19-year-old female patient with a complaint of mobile teeth in the left frontal region of the upper jaw. On clinical examination, unilateral cleft alveolus was observed between the left lateral incisor and the canine region. A multidisciplinary approach was adopted, orthodontic treatment was started, and periodontal regenerative surgery was planned. This report also discusses the substitution of autogenous bone grafts with other materials such as allogenic grafts (demineralized freeze-dried bone allograft), platelet-rich plasma, platelet-rich fibrin membranes, and amnion membranes, which could serve as a new line of treatment for the condition.

Cleft alveolus, a common birth defect of the maxillary bone, affects one in 700 live births every year. This defect is traditionally restored by autogenous bone grafts or allografts, which may possibly cause complications. Cell-based therapies using the mesenchymal stem cells (MSCs) derived from human gingiva (gingiva-derived mesenchymal stem cells [GMSCs]) is attracting the research interest due to their highly proliferative and multilineage differentiation capacity. Undifferentiated GMSCs expressed high level of MSC-distinctive surface antigens, including CD73, CD105, CD90, and CD166. Importantly, GMSCs induced with osteogenic medium for a week increased the surface markers of osteogenic phenotypes, such as CD10, CD92, and CD140b, indicating their osteogenic potential. The objective of this study was to assess the bone regenerative efficacy of predifferentiated GMSCs (dGMSCs) toward an osteogenic lineage in combination with a self-assembling hydrogel scaffold PuraMatrix™ (PM) and/or bone morphogenetic protein 2 (BMP2), on a rodent model of maxillary alveolar bone defect. A critical size maxillary alveolar defect of 7 mm × 1 mm × 1 mm was surgically created in athymic nude rats. The defect was filled with either PM/BMP2 or PM/dGMSCs or the combination of three (PM/dGMSCs/BMP2) and the bone regeneration was evaluated at 4 and 8 weeks postsurgery. New bone formation was evaluated by microcomputed tomography and histology using Hematoxylin and Eosin staining. The results demonstrated the absence of spontaneous bone healing, either at 4 or 8 weeks postsurgery in the defect group. However, the PM/dGMSCs/BMP2 group showed significant enhancement in bone regeneration at 4 and 8 weeks postsurgery, compared with the transplantation of individual material/cells alone. Apart from developing the smallest critical size defect, results showed that PM/dGMSCs/BMP2 could serve as a promising option for the regeneration of bone in the cranio/maxillofacial region in humans.

BACKGROUND: The habit of inserting foreign objects into body cavities is seen in children and in adults with intellectual disability. Usually, the foreign objects cause chronic inflammation and local tissue destruction, which give rise to symptoms. Diagnosis at an asymptomatic stage is uncommon when the history is not suggestive. We describe a rare case where a foreign object was misdiagnosed as an odontoma in a patient with an alveolar cleft.
METHODS: A radiopaque round mass was noted on the radiograph of a 12-year-old Sinhalese boy who was awaiting an alveolar bone graft. Apart from problems related to the alveolar cleft and mild halitosis, he was otherwise healthy. This was suspected to be an odontoma in the cleft region. During alveolar bone graft surgery, a button battery was recovered that was later confirmed as having been self-inserted by the child. Alveolar bone graft surgery was delayed because of local chronic inflammation due to the foreign object. Three months later, complete healing of the site was noted when reexplored for alveolar bone grafting.
CONCLUSIONS: It is important to include foreign objects in the radiological differential diagnosis in asymptomatic children. Furthermore, cone beam computed tomography should be considered in suspected cases. Early removal with thorough debridement causes minimal tissue destruction.

BACKGROUND: Alveolar cleft osteoplasty (ACO) using autologous bone grafts, is used worldwide as a standard treatment in the management of patients with clefts. Harvesting of the various autologous bone grafts is accompanied by considerable donor-site morbidity. Use of scaffold-based tissue engineering in ACO could potentially provide treatment options with decreased, or no donor-site morbidity. This study aims to demonstrate the technical and cell biological feasibility of using scaffold-based tissue engineering in ACO.
METHODS: Pre-existing cone-beam computed tomography scans were used for 3D printing of custom-made scaffolds (tricalcium phosphate-polyhydroxybutyrate (TCP-PHB)) according to the individual geometry of the alveolar bone in patients with clefts. The scaffolds were seeded with commercially available human mesenchymal stem cells (hMSCs). Cell survival and cell proliferation was monitored by live-dead assay, scanning electron microscopy (SEM) and WST-1 assay. The osteogenic differentiation of hMSCs on the scaffolds was evaluated by alkaline phosphatase (ALP) assay.
RESULTS: The custom-made scaffolds were nearly identical to the size and shape of the digital master. Approximately 91% of the subsequently applied mesenchymal stem cells could be seeded on the rails. We could demonstrate successful cell proliferation by a factor of 5-7 over the first 3 weeks. SEM showed a pore-border growth of the hMSCs on the scaffolds after 3 weeks of cell proliferation. The successful osteogenic differentiation of the scaffold-seeded cells could be demonstrated.
CONCLUSIONS: The concept of scaffold-based tissue engineering provides great potential as an alternative for the present gold standard of autologous bone grafts in ACO. The treatment causes less morbidity and is less invasive for managing young patients with cleft alveolar bone defects. Further in vivo studies and clinical trials are needed to demonstrate the advantages of this novel treatment for ACO in the clinical setting.