Mechanoresponsive regulation of tissue regeneration during distraction osteogenesis.

Distraction osteogenesis is widely used for bone tissue engineering. Mechanical stimulation plays a central role in the massive tissue regeneration observed during distraction osteogenesis. Although distraction osteogenesis has been a boon for patients with bone defects, we still have limited knowledge about the intrinsic mechanotransduction that converts physical forces into biochemical signals capable of inducing cell behavior changes and new tissue formation. In this review, we summarize the findings for mechanoresponsive factors, including cells, genes, and signaling pathways, during the distraction osteogenesis different phases. These elements function for coupling of osteogenesis and angiogenesis via the Integrin-FAK, TGF-ß/BMP, Wnt/ß-catenin, Hippo, MAPK, PI3K/Akt, and HIF-1α signaling pathways in a mechanoresponsive niche. The available evidence further suggests the existence of a balance between the epithelial-mesenchymal transition and mesenchymal-epithelial transition under hypoxic stress. We also briefly summarize the current in silico simulation algorithms and propose several future research directions that may advance understanding of distraction osteogenesis in the era of bioinformation, particularly the integration of artificial intelligence models with reliable single-cell RNA sequencing datasets. The objective of this review is to utilize established knowledge to further optimize existing distraction protocols and to identify potential therapeutic targets.

Spectrum of Disease in Hospitalized Newborns with Congenital Micrognathia: A Cohort of 3,236 Infants at North American Tertiary-Care Intensive Care Units.

OBJECTIVE: To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers. STUDY DESIGN: The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge. RESULTS: Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both). CONCLUSIONS: Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.

Vertical Alveolar Ridge Regeneration by Means of Periosteal Activation-A Proof-of-Principle Study.

AIM: To assess the possibility of vertical alveolar ridge augmentation by means of activation of the periosteum. MATERIALS AND METHODS: Six adult male Beagle dogs were used for the study. All premolars and first molars were extracted, and one vertical saucer-shaped bony defect was created on each side of the mandible. After 3 months of healing, full-thickness muco-periosteal flaps were elevated, and one distraction device was placed on each side of the mandible. The distraction plate was left submerged, and the activation mechanism connected to the distraction rod was exposed intra-orally. The protocol of periosteal activation (PP: periosteal 'pumping') was initiated after a latency of 7 days. The alternation of activation and relaxation at the rate of 0.35 mm/12 h during 5 days was followed by the sole activation of 0.35 mm/12 h for 5 days (PP group). Devices were left inactivated on the contralateral control side of the mandible (C group). All animals were euthanized after 8 weeks of consolidation. Samples were analysed histologically and by means of micro-CT. RESULTS: New mature lamellar bone was formed over the pristine bone in all groups. More intensive signs of bone modelling and remodelling were observed in the PP group compared to the C group. Mean new bone, bone marrow, connective tissue and total volumetric densities were greater in the PP group (p < 0.001, p = 0.001, p = 0.003 and p < 0.001, respectively). No differences were observed in the relative area parameters. Total tissue volume and bone volume were higher in the PP group (p = 0.031 and p = 0.076, respectively), while the bone mineral densities were higher in the C group (p = 0.041 and p = 0.003, respectively). Trabecular number, trabecular thickness and trabecular separation values were similar between the two groups. CONCLUSIONS: Regeneration of vertical alveolar bone ridge defects may be enhanced by activation of the periosteum, without the application of bone grafting materials.

Enhanced Bone Regeneration through Regulation of Mechanoresponsive FAK-ERK1/2 Signaling by ZINC40099027 during Distraction Osteogenesis.

Background: Focal adhesion kinase (FAK) is activated by mechanical stimulation and plays a vital role in distraction osteogenesis (DO), a well-established but lengthy procedure for repairing large bone defects. Both angiogenesis and osteogenesis contribute to bone regeneration during DO. However, the effects of ZINC40099027 (ZN27), a potent FAK activator, on angiogenesis, osteogenesis, and bone regeneration in DO remain unknown. Methods: The angiogenic potential of human umbilical vein endothelial cells (HUVECs) was evaluated using transwell migration and tube formation assays. The osteogenic activity of bone marrow mesenchymal stem cells (BMSCs) was assessed using alkaline phosphatase (ALP) and alizarin red s (ARS) staining. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence staining were used to assay angiogenic markers, osteogenic markers, and FAK-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In vivo, a rat tibia DO model was established to verify the effects of ZN27 on neovascularization and bone regeneration using radiological and histological analyses. Results: ZN27 promoted the migration and angiogenesis of HUVECs. Additionally, ZN27 facilitated the osteogenic differentiation of BMSCs, as revealed by increased ALP activity, calcium deposition, and expression of osteogenesis-specific markers. The ERK1/2-specific inhibitor PD98059 significantly hindered the effects of ZN27, suggesting the participation of FAK-ERK1/2 signaling in ZN27-enhanced angiogenesis and osteogenesis. As indicated by improved radiological and histological features, ZN27 induced active angiogenesis within the distraction area and accelerated bone regeneration in a rat DO model. Conclusion: Our results show that ZN27 targets FAK-ERK1/2 signaling to stimulate both angiogenesis and osteogenesis, and ZN27 accelerates bone regeneration in DO, suggesting the therapeutic potential of ZN27 for repairing large bone defects in the mechanobiological environment during DO.

Early posterior vault distraction osteogenesis changes the syndromic craniosynostosis treatment paradigm: long-term outcomes of a 23-year cohort study.

BACKGROUND: Early surgical management of syndromic craniosynostosis varies widely between centers, with patients typically undergoing multiple intracranial procedures through childhood. This study evaluates the long-term impact of early posterior vault distraction osteogenesis (PVDO) versus conventional treatment paradigms on the number and timing of subsequent craniofacial procedures. METHODS: We retrospectively analyzed the longitudinal operative patterns of patients with syndromic craniosynostosis treated from 2000 to 2023 with greater than five years of follow-up. Outcomes of patients who underwent early PVDO and conventional vault reconstruction were compared. RESULTS: Fifty-five patients met the inclusion criteria (30 PVDO and 25 conventional). Age at initial vault surgery was similar between the PVDO and conventional cohorts (7.6 vs. 8.8 months), as were baseline craniometrics (p > 0.05). Multiple fronto-orbital advancement (FOA) procedures were performed in only 1/30 (3%) PVDO-treated patient versus 12/25 (48%) conventionally-treated patients (p < 0.001). Twelve (40%) PVDO-treated patients did not undergo FOA at all. Among patients with Apert and Crouzon syndromes, fewer PVDO-treated patients required FOA prior to midface surgery (33% vs. 92%, p = 0.004) or repeat FOA (6% vs. 50%, p = 0.005) compared to conventionally-treated patients. Among patients with Muenke and Saethre-Chotzen syndromes, a similar proportion of patients required FOA in the PVDO and conventional cohorts (91% vs. 100%, p = 0.353), though no PVDO-treated patients required repeat FOA (0% vs. 44%, p = 0.018). CONCLUSIONS: Early PVDO is associated with a reduction in the high burden of both FOA and, critically, revisionary frontal procedures which are commonly seen in conventionally-treated patients with syndromic craniosynostosis.

Evaluation of post-activation mandibular remodelling in children with craniofacial microsomia treated with distraction osteogenesis.

OBJECTIVE: Patients with type IIA craniofacial microsomia (CFM) may benefit from mandibular distraction osteogenesis (MDO) treatment during childhood; however, remodelling of the mandible during the consolidation phase, which may affect the short-term outcomes of MDO, has not yet been quantitatively analysed using computed tomography. Therefore, we aimed to investigate bone remodelling of the mandible in children with type IIA CFM treated with MDO before distractor removal and the factors that influence ramus vertical elongation efficiency. MATERIALS AND METHODS: Twenty-three children with unilateral CFM were studied between 2020 and 2024. Longitudinal computed tomography data (preoperative, end of active phase and at pre-distractor removal) were analysed. Condyle positions and the mandibular cant were analysed using a paired-sample t test. The relapse rates of vertical lengthening and mandibular cant were calculated. The correlation between distraction efficiency and preoperative craniofacial morphology was analysed. RESULTS: The condyle on the affected side moved upwards and backwards by 28.84 ± 4.08 and 2.85 ± 4.33 mm, respectively during the active phase but lost 7.66 ± 2.64 mm of vertical extension during the consolidation phase. The relapse rates for vertical extension of the condyle and occlusal plane were 27% and 35%, respectively. The ratio of mandibular ramus height was positively related to EV. CONCLUSIONS: In children with CFM, attention should be paid to vertical elongation instability and relapse of mandibular inclination during consolidation. Severe mandibular ramus hypoplasia is a preoperative risk factor for vertical skeletal relapse during consolidation. Further efforts are required to reduce the stress that leads to relapse.

Trifocal versus Pentafocal bone transport in segmental tibial defects: a matched comparative analysis for posttraumatic osteomyelitis treatment.

PURPOSE: The objective of this study was to evaluate and compare the effectiveness and clinical results of trifocal bone transport (TBT) and pentafocal bone transport (PBT) in treating distal tibial defects > 6 cm resulting from posttraumatic osteomyelitis, highlighting the potential advantages and challenges of each method. METHODS: A retrospective assessment was conducted on an overall population of 46 eligible patients with distal tibial defects > 6 cm who received treatment between January 2015 and January 2019. Propensity score analysis was used to pair 10 patients who received TBT with 10 patients who received PBT. The outcomes assessed included demographic information, external fixation time (EFT), external fixation index (EFI), bone and functional outcomes assessed using the Association for the Study and Application of the Method of Ilizarov (ASAMI) scoring system, and postoperative complications evaluated using the Paley classification. RESULTS: The demographic and baseline data of the two groups were comparable. Following radical debridement, the average tibial defect was 7.02 ± 0.68 cm. The mean EFT was significantly shorter in the PBT group (130.9 ± 16.0 days) compared to the TBT group (297.3 ± 14.3 days). Similarly, the EFI was lower in the PBT group (20.67 ± 2.75 days/cm) than in the TBT group (35.86 ± 3.69 days/cm). Both groups exhibited satisfactory postoperative bone and functional results. Pin site infection was the most common complication and the rates were significantly different between the groups, with the PBT group demonstrating a higher incidence. CONCLUSION: Both TBT and PBT effectively treat posttraumatic tibial defects greater than 6 cm, with PBT offering more efficient bone regeneration. However, PBT is associated with a higher rate of pin site infections, highlighting the importance of careful management in these complex procedures and emphasizing the need for expert surgical execution and tailored treatment approaches in orthopedic reconstructive surgery.

Application of the MicroNAPS Classification for Robin Sequence.

OBJECTIVE: The only findings consistent among infants with Robin sequence (RS) are the presence of micrognathia, glossoptosis, and upper airway obstruction (UAO). Feeding and growth dysfunction are typical. The etiopathogenesis of these findings, however, is highly variable, ranging from sporadic to syndromic causes, with widely disparate levels of severity. This heterogeneity has created inconsistency within RS literature and debate about appropriate workup and treatment. Despite several attempts at stratification, no system has been broadly adopted. DESIGN: We recently presented a novel classification that is summarized by the acronym MicroNAPS. Each of 5 elements is scored: Micrognathia, Nutrition, Airway, Palate, Syndrome/comorbidities, and element scores are summarized into a "stage". RESULTS: Testing of this system in a sample of 100 infants from our center found it to be clinically relevant and to predict important management decisions and outcomes. CONCLUSIONS: We herein present an interactive website (www.prscalculator.com) and printable reference card for simple application of MicroNAPS, and we advocate for this classification system to be adopted for clinical care and research.

Clinical compatibility of magnetic resonance imaging with magnetic intramedullary nails: a feasibility study.

INTRODUCTION: The use of magnetic resonance imaging (MRI) with a magnetic intramedullary lengthening nail in place is contraindicated per the manufacturer due to the concern of implant activation and migration. A prior in vitro study did not confirm these complications only noting that a 3.0 T MRI weakened the internal magnet. Therefore, a retrospective analysis of patients who underwent an MRI with a magnetic nail in place was performed to determine if any adverse effects occurred in the clinical setting. MATERIALS AND METHODS: A retrospective review of all patients who underwent an MRI with a magnetic lengthening nail in place was performed. The time spent being imaged in the MRI, number of times the patient entered the MRI suite, and the images obtained were recorded. Radiographs were performed before and after the MRI to determine if any hardware complications occurred. The patients were monitored for any adverse symptoms while they were in the suite. RESULTS: A total of 12 patients with 13 nails were identified. Two patients underwent imaging with a 3.0 T MRI while the remaining 10 underwent imaging with a 1.5 T MRI. Each patient entered the MRI suite 2.1 times and spent an average of 84.7 min being imaged in the MRI (range 21-494). No patients noted any adverse symptoms related to the nail while in the suite and no hardware complications were identified. CONCLUSION: MRI appears to be safe with a magnetic nail in place and did not result in any complications. Given the manufacturer's recommendations, informed consent should be obtained prior to an MRI being performed and a 3.0 T MRI should be avoided when possible if further activation of the nail is required.

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report.

BACKGROUND: Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients' lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. CASE PRESENTATION: Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. CONCLUSIONS: ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

Efficacy of modified anterior maxillary segmental distraction osteogenesis based on 3D visualisation for the treatment of maxillary hypoplasia among adolescents with cleft lip and palate.

BACKGROUND: This study evaluates a three-dimensional (3D) visualisation design combined with customized surgical guides to assist anterior maxillary segmental distraction osteogenesis (AMSDO) in correcting maxillary hypoplasia in adolescents with cleft lip and palate (CLP), focusing on treatment outcomes, satisfaction and the validity of 3D planning. METHODS: This retrospective cohort study was conducted at a single hospital in China. Between January 2020 and December 2023, 12 adolescents with CLP with maxillary hypoplasia were included. An advanced 3D simulation was used to convey the treatment strategy to the patients and their families. A customized surgical guide and distraction osteogenesis device were designed. Cephalometric analysis evaluated AMSDO changes and long-term stability. Patient satisfaction was assessed. The Chinese version of the Child Oral Health Impact Profile was used to evaluate the children's oral health-related quality of life before and after treatment. The postoperative outcomes were compared with the planned outcomes by superimposing the actual postoperative data onto the simulated soft tissue models and calculating the linear and angular differences between them. RESULTS: One patient experienced postoperative gingivitis, yielding an 8.33% complication rate. Most patients (83.33%) were highly satisfied with the target position, with the rest content. Cephalometric analysis showed significant improvements in various indices post-traction. Quality-of-life scores significantly improved post-treatment. The discrepancies in facial soft tissue between the simulated and actual results were within clinically satisfactory ranges. CONCLUSIONS: Digitally designed surgical guides effectively treat maxillary hypoplasia in adolescents with CLP, ensuring stability, reducing complications, reducing dependency on operator experience, and enhancing satisfaction and health outcomes. Although the simulated results were clinically acceptable, it is important to inform patients of potential variations in the predicted soft tissue.

Multidisciplinary treatment of a patient with TMJ ankylosis and a severe dentofacial discrepancy: A case report.

INTRODUCTION: Temporomandibular joint (TMJ) ankylosis is a debilitating condition characterised by the fusion of bony or fibrous tissues in the TMJ, resulting in restricted mouth opening, functional challenges and facial deformities. This report highlights the complexity and multifaceted nature of TMJ ankylosis and emphasises the significance of early intervention and a multidisciplinary approach. Distraction osteogenesis has emerged as a successful method for managing TMJ ankylosis and associated facial asymmetry. Post-distraction orthodontic management is essential to address occlusal changes, including posterior open bite and crossbite. DIAGNOSIS AND TREATMENT PLAN: A 17-year-old boy with unilateral right-sided TMJ ankylosis presented with restricted mouth opening, facial asymmetry and functional difficulties. Multidisciplinary treatment planning involved distraction osteogenesis, condylectomy, coronoidectomy and orthodontic correction to achieve proper occlusion and facial aesthetics. RESULTS: The treatment significantly improved facial aesthetics, mouth opening, occlusion and the patient's confidence and self-esteem. CONCLUSION: This case report underscores the complexity of TMJ ankylosis and the need for a comprehensive approach, including surgical and orthodontic interventions. Collaboration among healthcare professionals and ongoing research is vital to refine treatment approaches and improve the quality of life for patients with TMJ ankylosis.

Skeletal expansion via craniofacial distraction osteogenesis technique in syndromic craniosynostosis: impact on ophthalmic parameters.

BACKGROUND: This study aims to compare the changes in ophthalmic parameters among syndromic craniosynostosis patients who underwent craniofacial skeletal expansion procedures via distraction osteogenesis (DO). METHOD: A retrospective study was conducted involving syndromic craniosynostosis patients who underwent surgical expansion via the DO technique from the year 2012 to March 2022. Changes in six parameters which consist of visual acuity, refractive error, optic disc health, intraocular pressure, degree of proptosis and orbital volume were measured objectively pre and post-surgery. For categorical parameters, the Chi-square cross-tab test was done. Paired sample T-test was used for normally distributed variables. Wilcoxon signed-rank test was used for non-normally distributed data. RESULTS: Visual impairment was present in 21.4% of eyes before surgery and increased to 28.5% post-surgery. Three patients had changes of refractive error post-surgery with one developed hypermetropia, another developed anisometropia and the last had improvement to no refractive error. Two patients had optic disc swelling which was resolved post-surgery. Intraocular pressure changes were inconsistent post-surgery. All patients achieved a significant reduction in the degree of proptosis post-surgery. Orbital volume calculation using computed tomography (CT) scans shows a significant increase in volume post-surgery for all patients. CONCLUSION: Our study shows a significant increase in orbital volume post-surgery with a reduction in the degree of proptosis. Optic disc and nerve health improved after the surgery. Changes in terms of visual acuity, refractive error and IOP were inconsistent after the surgical intervention.

Determination of mandibular distraction osteogenesis most suitable parameters. An experimental study.

BACKGROUND: Distraction osteogenesis is a process of induced bone generation. Various protocols have been described for the management of the latency period, distraction speed and consolidation period, with greater or lesser success. OBJECTIVE: To better understand the process of mandibular distraction and establish the determining factors and their optimal times. MATERIAL AND METHODS: Twenty-seven dogs were studied, which had 54 distractors placed and that underwent unidirectional, bilateral mandibular distraction osteogenesis. The distraction processes were applied using six variants, two for each factor: latency period, distraction period and distraction speed. The changes were examined by means of bone biopsies and X-rays of the area at 0, 7, 14, 21, 45 and 55 days of the process. RESULTS: The most efficient osteogenic distraction parameters were a latency period of five days, a consolidation period of six weeks, distraction speed of 1 mm/day for distances of less than 20 mm, and 3 mm/day for longer distances. CONCLUSIONS: The sequential histological study allowed to observe the appearance of cellular elements (osteocytes, osteoclasts, osteoid matrix, trabeculate, etc.) and their participation in granulation tissue, newly-formed bone and compact mature bone.

ANTECEDENTES: Respecto a la distracción osteogénica (generación ósea inducida), con mayor o menor éxito han sido descritos diversos protocolos para el manejo del período de latencia, velocidad de distracción y período de consolidación. ­. OBJETIVO: Entender mejor el proceso de la distracción mandibular y establecer los factores determinantes y sus tiempos óptimos. MATERIAL Y MÉTODOS: Se estudiaron 27 perros sometidos a distracción osteogénica unidireccional, bilateral de la mandíbula. Los procesos de distracción se aplicaron con seis variantes, dos por cada factor (período de latencia, período de distracción y velocidad de distracción). Se estudiaron los cambios mediante biopsias del hueso y radiografías de la zona a los 0, 7, 14, 21, 45 y 55 días del proceso. RESULTADOS: Los parámetros de distracción osteogénica más eficientes fueron período de latencia de cinco días, período de consolidación de seis semanas, 1 mm diario de velocidad de distracción para distancias menores a 20 mm y 3 mm diarios para distancias mayores. CONCLUSIONES: El estudio histológico secuencial permitió observar la aparición de los elementos celulares (osteocitos, osteoclastos, matriz osteoide, trabeculado, etcétera) y su participación en el tejido de granulación, el hueso neoformado y el hueso maduro compacto.

The effect of intermittent parathyroid hormone on bone lengthening: current evidence to inform future effective interventions.

PURPOSE: Recent studies have demonstrated the positive effects of parathyroid hormone (PTH) on bone healing, and findings support the use of PTH to accelerate bone healing following distraction osteogenesis. The goal of this review was to compile and discuss the mechanisms potentially underlying the effects of PTH on newly formed bone following a bone-lengthening procedure incorporating all relevant evidence in both animal and clinical studies. METHODS: This review summarized all evidence from in vivo to clinical studies regarding the effects of PTH administration on a bone-lengthening model. In addition, a comprehensive evaluation of what is currently known regarding the potential mechanisms underlying the potential benefits of PTH in bone lengthening was presented. Some controversial findings regarding the optimal dosage and timing of administration of PTH in this model were also discussed. RESULTS: The findings demonstrated that the potential mechanisms associated with the action of PTH on the acceleration of bone regeneration after distraction osteogenesis are involvement in mesenchymal cell proliferation and differentiation, endochondral bone formation, membranous bone formation, and callus remodeling. CONCLUSIONS: In the last 20 years, a number of animal and clinical studies have indicated that there is a prospective role for PTH treatment in human bone lengthening as an anabolic agent that accelerates the mineralization and strength of the regenerated bone. Therefore, PTH treatment can be viewed as a potential treatment to increase the amount of new calcified bone and the mechanical strength of the bone in order to shorten the consolidation stage after bone lengthening.

High-mobility group box 1 accelerates distraction osteogenesis healing via the recruitment of endogenous stem/progenitor cells.

BACKGROUND AIMS: While distraction osteogenesis (DO) achieves substantial bone regeneration, prolonged fixation may lead to infections. Existing stem cell and physical therapies have limitations, requiring the development of novel therapeutic approaches. Here, we evaluated high-mobility group box 1 (HMGB1) as a novel therapeutic target for DO treatment. METHODS: Micro-computed tomography (Micro-CT) analysis and histological staining of samples obtained from tibial DO model mice was performed. Transwell migration, wound healing, and proliferation assays were also performed on cultured human mesenchymal stem cells (hMSCs) and human umbilival vein endothelial cells (HUVECs). Tube formation assay was performed on HUVECs, whereas osteogenic differentiation assay was performed on hMSCs. RESULTS: Micro-CT analysis and histological staining of mouse samples revealed that HMGB1 promotes bone regeneration during DO via the recruitment of PDGFRα and Sca-1 positve (PαS+) cells and endothelial progenitor cells. Furthermore, HMGB1 accelerated angiogenesis during DO, promoted the migration and osteogenic differentiation of hMSCs as well as the proliferation, migration and angiogenesis of HUVECs in vitro. CONCLUSIONS: Our findings suggest that HMGB1 has a positive influence on endogenous stem/progenitor cells, representing a novel therapeutic target for the acceleration of DO-driven bone regeneration.

Indications and surgical technique for distraction osteogenesis of the alveolar bone for augmentation prior to insertion of dental implants.

When bone is limited, short, ultra-short, or narrow implants help to restore oral rehabilitation with an acceptable long-term outcome. This becomes more difficult with severe vertical bone loss. Guided bone regeneration, onlay block transplantation, or sandwich osteotomy have been established to build up these defects. The alternative to the alveolar distraction osteogenesis (ADO) has only been established in some centers, with a standardized protocol. On the one hand, ADO is a biological procedure that allows almost a "restitutio ad integrum" when building up hard and soft tissue. On the other hand, there are clear indications, limitations, and complications of the procedure in the literature. In addition to the literature, concept of Tissue Regeneration by Alveolar Callusdistraction Cologne (TRACC), which has been practiced successfully for over two decades, will be presented for different indications.

The management of upper airway obstruction in Pierre Robin Sequence.

Pierre Robin Sequence (PRS) is defined by a constellation of characteristics including micrognathia, glossoptosis and airway obstruction. PRS can occur in isolation or can be associated with syndromes and another anomalies. Airway obstruction and feeding difficulties are the major presenting issues, and the severity of the condition ranges from mild, with minimal to no symptoms, to severe, with overt obstruction resulting in apnoeas, severe respiratory distress and cyanosis. The presence of airway obstruction can result in obstructive sleep apnoea and abnormalities in gas exchange, as well as exacerbation of already present feeding difficulties and failure to thrive, secondary to mismatch of caloric intake to energy usage associated with increased effort of breathing. Management of airway obstruction for infants with PRS varies between centres. This paper explores the surgical and non-surgical management options available, their effectiveness and pitfalls in children with PRS. Despite the pros and cons of each management option, it is evident that resource availability and multidisciplinary clinical support are key factors to successful management.

What changes in maxillary morphology from distraction osteogenesis maxillary expansion (DOME) correlate with subjective and objective OSA measures?

OBJECTIVES: To correlate skeletal and airway measures on imaging with polysomnographic and self-reported measures after distraction osteogenesis maxillary expansion (DOME), in the effort to identify clinically relevant sites of expansion to guide treatment for adult patients with obstructive sleep apnea (OSA). MATERIALS AND METHODS: This is a retrospective study reviewing subjects who underwent DOME and had the complete set of the following data: peri-treatment cone-beam computed tomography (CBCT) scans, polysomnography (PSG), Epworth Sleepiness Scale (ESS), and nasal obstruction symptom (NOSE) scores. RESULTS: Of 132 subjects who underwent DOME, 35 met inclusion criteria (71% men, mean age 27.7 ± 6.5 years, mean BMI 26.0 ± 6.4 kg/m2) and were enrolled in the study. There was a significant reduction in the NOSE score from 11.4 ± 5.5 to 3.6 ± 3.1, in the ESS score from 12.0 ± 4.6 to 7.1 ± 4.7, and in the apnea-hypopnea index (AHI) from 17.1 ± 15.8 to 7.01 ± 6.2 (p < 0.0001), after DOME. Nasal floor width at the nasopalatine canal level showed a statistically significant correlation with AHI reduction (p < .0001). CONCLUSIONS: DOME is significantly associated with reduction of nasal obstruction, sleepiness, and severity of OSA. The findings suggest that expansion at the anterior third of the bony nasal passage, specifically where the nasopalatine canal is located predicts its clinical efficacy. This site may be a useful target anatomically via imaging.

Long-term aesthetic and photogrammetric outcomes in non-syndromic unicoronal synostosis: comparison of fronto-orbital distraction osteogenesis and fronto-orbital advancement and remodeling.

BACKGROUND: Fronto-orbital advancement and remodeling (FOAR) is among the most common surgical approaches for unicoronal craniosynostosis (UCS), although some data demonstrate failure to achieve long-term aesthetic normalcy, leading some to seek alternative treatment paradigms such as fronto-orbital distraction osteogenesis (FODO). This study compares long-term aesthetic outcomes of patients with UCS treated with FOAR and FODO. METHODS: Twenty patients (four males) with non-syndromic UCS presenting to our institution and undergoing distraction were compared to a matched cohort of 20 patients (six males) undergoing FOAR. Clinical photographs and ImageJ were used to quantify periorbital anatomy including palpebral fissures, pupil-to-brow distance (PTB), and margin-reflex distance (MRD1) in pixels. Whitaker classification was blindly assigned by craniofacial surgeons. RESULTS: Photogrammetric analysis and Mann-Whitney U tests demonstrated significantly improved postoperative symmetry in distraction patients for palpebral width (p = 0.020), MRD1 (p = 0.045), and canthal tilt (p = 0.010). Average Whitaker classification scores between FOAR (1.94) and distraction (1.79) cohorts were similar (p = 0.374). CONCLUSIONS: UCS patients demonstrated significant postoperative improvements in periorbital symmetry, with distraction patients demonstrating superior results in palpebral width and canthal tilt. FOAR and FODO patients achieved similar Whitaker classification scores. These cohorts will be followed until craniofacial maturity prior to making any definitive conclusions.