The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats.

Bone regeneration and mineralization can be achieved by means of distraction osteogenesis (DO). In the present study, we investigated the effect of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on the new bone formation during DO in rats. Forty-eight Sprague-Dawley rats were randomized into four groups of 12 rats each. We established the left femoral DO model in rats and performed a mid-femoral osteotomy, which was fixed with an external fixator. DO was performed at 0.25 mm/12 h after an incubation period of 5 days. Distraction was continued for 10 days, resulting in a total of 5 mm of lengthening. After distraction, the solution was locally injected into the osteotomy site, once a day 1 ml for 1 week. One group received the solvent alone and served as the control, and the other three groups were treated with SDF-1, VEGF, and SDF-1with VEGF in an aqueous. Sequential X-ray radiographs were taken two weekly. The regeneration was monitored with the use of micro-CT analysis, mechanical testing, and histology. Radiographs showed accelerated regenerate ossification in the SDF-1, VEGF, and SDF-1 with the VEGF group, with a larger amount of new bone compared with the control group, especially SDF-1 with the VEGF group. Micro-CT analysis and biomechanical tests showed Continuous injection of the SDF-1, VEGF, and SDF-1 with VEGF during the consolidation period significantly increased bone mineral density bone volume, mechanical maximum loading, and bone mineralization of the regenerate. Similarly, the expression of osteogenic-specific genes, as determined by real-time polymerase chain reaction , was significantly higher in SDF-1 with the VEGF group than in the other groups. Histological examination revealed more new trabeculae in the distraction gap and more mature bone tissue for the SDF-1 with the VEGF group. SDF-1 and VEGF promote bone regeneration and mineralization during DO, and there is a synergistic effect between the SDF-1 and VEGF. It is possible to provide a new and feasible method to shorten the period of treatment of DO.

Novel patient-specific helical maxillary distractor: an in vitro feasibility study.

At present, stock linear distractors are used for internal maxillary distraction osteogenesis. However, the authors' research group has demonstrated, through an in silico analysis, that linear distraction leads to bone deformities and malocclusion, whereas helical distraction can yield ideal outcomes. A system for designing and manufacturing custom helical distractors has recently been developed, and the feasibility of these appliances now needs to be assessed. This study was, therefore, conducted to gain an initial insight into their feasibility. The study had two goals. First, it aimed to demonstrate, in an in vitro model, that the novel system of custom helical distraction can produce appropriate clinical outcomes. The second aim was to compare the performance of custom helical distractors with that of stock devices and hybrid devices (i.e., linear appliances that feature patient-specific footplates). Interpreting the results as trends, this study showed that the system of custom helical distraction resulted in in vitro outcomes that were superior to those obtained with stock and hybrid devices.

Distraction osteogenesis in combined sequential use of external fixation and nailing (lengthening and then nailing): An experimental study in rabbits.

Limb lengthening relies on the process of distraction osteogenesis. The active periosteal bone formation has been detected in clinical practice with a lengthening and then nail (LATN) technique but has not been confirmed by experimental studies to date. The aim of this study is to compare the tissue regeneration of the distraction regenerate during tibial lengthening in rabbits using a LATN technique. This study was performed on 54 mature rabbits of the Soviet Chinchilla breed, which were divided into three groups of 18 animals. In group 1 (control), the tibia was lengthened in an external fixator. In group 2, the LATN technique was modeled and in group 3, lengthening over nail (LON) was modeled. The total duration of the experiment was 45 days. On the 10th, 15th, 20th, 30th, and 45th day X-ray, computed tomography and morphological studies were performed. In the experimental groups (2 and 3), a more pronounced periosteal bone formation in the area of regenerate was noted when compared to group 1. In group 2 (LATN), wide cortical plates were formed from the intermediate and periosteal areas. In this group, the maximum densitometric density values were noted. Endosteal bone formation was preserved in all groups. The LON and LATN techniques, when compared with the classical Ilizarov lengthening, do not demonstrate any deficiency in the tissue regeneration of the bone tissue at the regenerate sites. The most powerful bone structures are formed with the sequential use of the external fixation and nailing (LATN).

H Vessel Formation as a Marker for Enhanced Bone Healing in Irradiated Distraction Osteogenesis.

In the setting of bone defects, the injured vasculature and loss of hemodynamic inflow leads to hematoma formation and low oxygen tension which stimulates vascular expansion through the HIf-1α pathway. Most importantly, this pathway upregulates sprouting of type H vessels (CD31hiEmcnhi vessels). H vessels engage in direct interaction with perivascular osteoprogenitor cells (OPCs), osteoblasts, and preosteoclasts of bone formation and remodeling. This angiogenic-osteogenic coupling leads to synchronous propagation of vascular and bony tissue for regenerative healing. A growing body of literature demonstrates that H vessels constitute a large portion of bone's innate capacity for osteogenic healing. We believe that CD31hiEmcnhi vessels play a role in bone healing during distraction osteogenesis (DO). DO is a procedure that utilizes traction forces to facilitate induction of endogenous bone formation and regeneration of surrounding soft tissues such as skin, muscle, tendon, and neurovascular structures. While the H vessel response to mechanical injury is adequate to facilitate healing in normal healthy tissue, it remains inadequate to overcome the devastation of radiation. We posit that the destruction of CD31hiEmcnhi vessels plays a role in precluding DO's effectiveness in irradiated bone defect healing. We aim, therefore, to recapitulate the normal pathway of bony healing by utilizing the regenerative capacity of H vessels. We hypothesize that using localized application of deferoxamine (DFO) will enhance the H vessel-mediated vasculogenic response to radiation damage and ultimately enable osteogenic healing during DO. This discovery could potentially be exploited by developing translational therapeutics to hopefully accelerate bone formation and shorten the DO consolidation period, thereby potentially expanding DO's utilization in irradiated bone healing. Sprague-Dawley rats were divided into three groups: DO, radiation with DO (xDO), and radiation with DO and DFO implantation (xDODFO). Experimental groups received 35 Gy of radiation. All groups underwent DO. The treatment group received injections into the osteotomy site, every other day, beginning on postoperative day (POD) 4 of DFO. Animals were sacrificed on POD 40. For immunohistochemical analysis, mandibles were dissected and fixed in 4% paraformaldehyde for 48 hours, decalcified in Cal-Ex II for 2 days, dehydrated through graded ethanol of increasing concentration, and then embedded in paraffin. Samples were cut into 7-µm thick longitudinally oriented sections including the metaphysis and diaphysis. CD31 and Emcn double immunofluorescent staining were performed to evaluate the extent of CD31hiEmcnhi vessel formation. Bone sections were then stained with conjugated antibodies overnight at 4°C. Nuclei were stained with Hoechst. Slides were also double stained with Osterix and CD31 to study the quantity of H vessel-mediated recruitment of OPCs to accelerate bone healing. Images were acquired with a Nikon Ti2 widefield microscope and analyzed in NIS- Elements Advanced Research 5.41.02 software. The abundance of type H vessels is represented by the area fraction of CD31 + Emcn+ vessel area inside the regenerate sample. OPC concomitant proliferation into the distraction gap is represented by the area fraction of Osterix+ cell area inside of the regenerate sample. There were 6× more type H vessels in DO groups than in xDO groups. Localized DFO significantly increased the abundance of type H vessels of irradiated DO animals compared to xDO by 15× ( p = 0.00133531). Moreover, the DO and xDODFO groups with higher abundance of type H vessels also demonstrated better angiogenesis and osteogenesis outcomes. Interestingly, xDODFO groups doubled the quantity of H vessel formation compared to DO, indicating a supraphysiologic response ( p = 0.044655055). Furthermore, H vessel-mediated recruitment of OPCs mimicked the described H vessel formation trend in our study groups. Irradiated DO groups contained 3× less OPCs compared to DO controls. DFO treatment to xDO animals remediated irradiation damage by containing 12× Osterix+ cells. Finally, DFO treatment of irradiated animals quadrupled osteoprogenitor recruitment into the distraction gap compared to DO controls. In this study, we developed a novel approach to visualize CD31hiEmcnhi in paraffin sections to study DO regeneration. Normal DO demonstrated a significant upregulation of H vessel formation and associated angiogenic-osteogenic coupling. Radiation severely decreased H vessel formation along with an associated significant diminution of new bone formation and nonunion. DFO administration, however, resulted in vascular replenishment and the restoration of high quantities of CD31hiEmcnhi and OPCs, recapitulating the normal process of bony regeneration and repair. DFO treatment remediated new bone formation and bony union in irradiated fields associated with increased H vessel angiogenic-osteogenic coupling. While further studies are required to optimize this approach, the results of this study are incredibly promising for the long-awaited translation of localized DFO into the clinical arena.

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.

TP508 Promotes Bone Regeneration on Distraction Osteogenesis via the Activation of Wnt/ß-catenin Signaling Pathway.

INTRODUCTION: TP508 is a thrombin peptide that participates in the inflammatory response and wound healing. Its role in the molecular mechanism of distraction osteogenesis remains unclear. This study established a tibia distraction osteogenesis (DO) model in rats and investigated the role and mechanism of TP508 in bone regeneration during DO. METHOD: Micro-computed tomography (Micro-CT) and hematoxylin-eosin (HE) staining were used to track osteogenesis. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to measure the expression of osteoblast-related factors, Wnt/ß- catenin signaling-related proteins and genes. Immunohistochemistry was used to measure the expression of ß-catenin in the cytoplasm and nucleus. TP508 accelerated bone regeneration increased the expression of the osteoblast-related factors Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). RESULTS: After the Wnt signaling was inhibited by LGK974, the expression of osteoblast-related factors was downregulated, leading to a decrease in bone regeneration ability. More importantly, TP508 upregulated ß-catenin and its target CYCLIN-D1 and could reverse the decreased osteogenic ability caused by LGK974. CONCLUSION: In conclusion, TP508 promotes bone regeneration in DO by activating the Wnt/ß- catenin signaling pathway.

Does distraction osteogenesis improve the airway volume and quality of life of obstructive sleep apnoea patients secondary to temporomandibular joint ankylosis?

Temporomandibular joint (TMJ) ankylosis leads to mandibular micrognathia that severely collapses the upper airway causing obstructive sleep apnoea (OSA), resulting in deterioration and compromise in the quality of life (QoL) of patients. In this study, we aimed to calculate airway volume changes, apnoea-hypopnoea index (AHI), and improvement in quality of life before and after distraction osteogenesis (DO). Fourteen Patients with OSA secondary to TMJ ankylosis at a mean (SD) age of 17.5 (5.43) years were enrolled in this prospective study. Multivector mandibular distractors were used in all patients following the standard Ilizarov distraction protocol with a mean (SD) anteroposterior distraction of 16.21 (4.37) mm and a consolidation period of 116.92 (14.35) days. The patients were followed up for six months. A polysomnography test (PSG) was done to quantify AHI and a low-dose computed tomographic scan was done to calculate airway volume using Dolphin medical imaging software pre and post-DO. The QoL of the patients was calculated using the OSA-18 questionnaire. Results analysis depicted that the mean (SD) preoperative AHI was 51.44 (37.99)/h which was improved to 9.57 (9.74)/h (p = 0.001) after DO. Airway volume was calculated on Dolphin software before and after DO showed a significant improvement in airway volume by 121.12% (98.30)%. Similarly, the OSA-18 questionnaire showed significant improvement in QoL from severe to normal. This study suggested that DO increases the corpus length of the mandible, leading to an increment in airway volume, which improves the QoL.

Management of bilateral condylar agenesis by distraction osteogenesis: a rare case report.

Condylar agenesis is a rare case involving developmental disturbances related to growth of mandible, facial aesthetics, dentition development, muscle deformation, and occlusal problems. As such, this is a rare condition, and there is no internationally accepted protocol for the same. Underdevelopment or defective formation of condyle may be congenital or acquired. Condylar agenesis is congenital non formation of condyle, while hypoplasia is poor development. We report a case of bilateral condylar agenesis in a 30-year-old female patient.

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.

Skeletal stability after maxillary distraction osteogenesis or conventional Le Fort I osteotomy in patients with cleft lip and palate: A superimposition-based cephalometric analysis.

PURPOSE: The aim was to assess skeletal stability after maxillary advancement using either distraction osteogenesis (DO) or conventional Le Fort I osteotomy (CO) in patients with cleft lip and palate (CLP) or cleft palate (CP) utilising a new superimposition-based cephalometric method. METHOD: This retrospective study included patients who were treated with DO (N = 12) or CO (N = 9). Sagittal and vertical changes after surgery, and skeletal stability at 18 months post-operatively were assessed with superimposition-based cephalometry, comparing lateral cephalograms performed pre-operatively (T0), post-operatively after CO or immediately after completed distraction in DO (T1), and at 18 months of follow-up (T2). RESULTS: The mean sagittal movements from T0 to T2 in the DO and CO groups were 5.9 mm and 2.2 mm, respectively, with a skeletal relapse rate of 16% in the DO group and 15% in the CO group between T1 and T2. The vertical mean movement from T0 to T2 in the DO and CO groups was 2.8 mm and 2.0 mm, respectively, and the skeletal relapse rate between T1 and T2 was 36% in the DO group and 32% in the CO group. CONCLUSION: Sagittal advancement of the maxilla was stable, in contrast to the vertical downward movement, which showed more-extensive relapse in both groups. Despite more-extensive maxillary advancement in the DO group, the rates of skeletal relapse were similar.

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.

Genioplasty and Hyoid Advancement by Distraction Osteogenesis for the Correction of Obstructive Sleep Apnea in a Pediatric Patient.

Advancement genioplasty is one variation of genioglossus advancement (GA) and GA is a surgical intervention that can be applied for obstructive sleep apnea (OSA) caused by hypopharyngeal collapse. The genioglossus muscle originates from the posterior surface of the midline mandible and inserts into the entire tongue mass and the body of the hyoid bone. Placing horizontal tension on the genioglossus muscle enlarges the posterior airway space. We use a modified GA that applies distraction osteogenesis to increase forward movement of the genioglossus muscle and also connects the bone transport segment to the hyoid bone with a thread to maximize the anterior movement of the hyoid bone. We used this technique on a young patient and obtained good results.

3D-CT measurements of facial symmetry in severe CFM patients: A comparative study between mandibular ascending ramus distraction osteogenesis and bone grafting.

This study aims to compare the effects of mandibular distraction osteogenesis (MDO) and bone grafting on the facial symmetry of children with Pruzansky-Kaban type IIB and III craniofacial microsomia (CFM). Medical records and three-dimensional computed tomography (3D-CT) data of CFM patients who had primarily undergone MDO and bone grafting were collected. A retrospective analysis of pre-and post-operative 3D imaging data was conducted to compare the improvement rate in facial symmetry between the two groups based on occlusal cant, affected/unaffected ramus height ratio and chin point deviation. The data were tested for normality using the Shapiro-Wilk test. When the data followed a normal distribution, a paired sample t-test was employed for the comparison between preoperative and postoperative data. When the data did not follow a normal distribution, the Wilcoxon signed-rank test for paired samples was used for preoperative and postoperative comparison. The study included 18 children with type IIB and III CFM, 11 in the MDO group and 7 in the bone grafting group. In the MDO group, postoperative Gn-FH and Gn-Cor distances increased significantly, whereas the postoperative Gn-Mid distance decreased significantly. Occlusal cant decreased significantly and ramus height affected/unaffected ratio increased significantly after MDO. In the bone graft group, there was no statistically significant difference in the postoperative ratios of chin deviation, occlusal cant, and ramus height affected/unaffected compared to the preoperative values. Compared to bone grafting, MDO can significantly enhance ramus height ratio, level occlusal plane, and centralize the chin point among patients with CFM. Furthermore, MDO achieves superior enhancements in facial symmetry.

Tensile Stress-Activated and Exosome-Transferred YAP/TAZ-Notch Circuit Specifies Type H Endothelial Cell for Segmental Bone Regeneration.

The Ilizarov technique has been continuously innovated to utilize tensile stress (TS) for inducing a bone development-like regenerative process, aiming to achieve skeletal elongation and reconstruction. However, it remains uncertain whether this distraction osteogenesis (DO) process induced by TS involves the pivotal coupling of angiogenesis and osteogenesis mediated by type H endothelial cells (THECs). In this study, it is demonstrated that the Ilizarov technique induces the formation of a metaphysis-like architecture composed of THECs, leading to segmental bone regeneration during the DO process. Mechanistically, cell-matrix interactions-mediated activation of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) transcriptionally upregulates the expression of Notch1 and Delta-like ligand 4, which act as direct positive regulators of THECs phenotype, in bone marrow endothelial cells (BMECs) upon TS stimulation. Simultaneously, the Notch intracellular domain enhances YAP/TAZ activity by transcriptionally upregulating YAP expression and stabilizing TAZ protein, thus establishing the YAP/TAZ-Notch circuit. Additionally, TS-stimulated BMECs secrete exosomes enriched with vital molecules in this positive feedback pathway, which can be utilized to promote segmental bone defect healing, mimicking the therapeutic effects of Ilizarov technique. The findings advance the understanding of TS-induced segmental bone regeneration and establish the foundation for innovative biological therapeutic strategies aimed at activating THECs.

Objective and subjective evaluation of the efficacy of trans-sutural distraction osteogenesis: A correlation analysis between computed tomography measurements and FACE-Q scores.

Previous studies on the efficacy of trans-sutural distraction osteogenesis (TSDO) to treat midface hypoplasia caused by cleft lip and palate (CLP) have mainly focused on objective measurements while ignoring the subjective feelings of patients. This study aimed to analyse the changes in and correlation between computed tomography (CT) measurements and FACE-Q scores in patients who underwent TSDO by performing a comprehensive evaluation from both objective and subjective perspectives. This retrospective study included 25 patients with an average age of 10.7 years who had midface hypoplasia caused by CLP and underwent TSDO between August 2018 and December 2022. The average follow-up time was 18.8 ± 7.7 months. Facial morphology and CT measurements, including A-CR, N-A⊥HR, the SNA angle and the L-ZA, indicated significant improvements in midface concavity (all p < 0.0001). All FACE-Q scores (except for facial function) exhibited a significant increase. The ΔA-CR, ΔN-A⊥HR, and ΔSNA angle were strongly correlated with specific aspects of the FACE-Q-Appearance items, including the ΔFACE-Q-Appearance of the cheeks (all p < 0.0001), the ΔFACE-Q-Appearance of the face (all p < 0.0001), the ΔFACE-Q-Appearance of the jaws (all p < 0.01), the ΔSatisfaction with decision (all p < 0.0001) and the ΔSatisfaction with outcome (all p < 0.001). However, the ΔA-CR, ΔN-A⊥HR, and ΔSNA were weakly correlated with other FACE-Q-Health-related quality of life and function items. These findings suggest that both CT findings and FACE-Q scores have their own emphases and advantages. It is necessary to establish an integrated curative effect evaluation model that combines FACE-Q scores with CT measurements to evaluate both the physical health and psychological status of patients.

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.

Comparative analysis of free vascularized fibula grafting and Ilizarov bone transport in management of segmental long bone defect of the lower limb: A systematic review and meta-analysis.

Introduction: Reconstruction of segmental defects of long bones is a daunting task for surgeons. Bone transport with the help of Illizarov external fixator and vascularized free fibula flap are some of the most discussed and valid options for the same. Both techniques have their limitations and overlapping indications. However, there has been no objective evidence in the manner of a systematic review supporting one treatment method over the other. Aim: This systemic review is aimed to compare the bony union, functional outcomes, and complications of Illizarov bone lengthening and free fibula flap performed for segmental bone defects of long bones of the leg. Methods: A comprehensive search was done for all studies published before May 2023. Any observational study comparing bone transport based on Illizarov external fixator and free vascularized fibula grafting techniques for treating lower limb long bone segmental defects was entailed in this study. Results: This systematic review comprised of five retrospective studies. A total of 96 patients were treated by the Illizarov-based bone transport technique and 72 patients were treated by the free vascularized fibula grafting technique. The free vascularized fibula grafting technique yielded a shorter mean time to union (average difference 9.3 months), relatively shorter external fixator time (average difference 5.32 months), and external fixator index (average difference 0.57 months/cm). However, there was no difference in terms of bony and functional outcomes between both techniques when used for the reconstruction of bony defects in the lower limb. Total number of complications was 68 % higher in bone transport with Illizarov external fixator. However, the rates of non-union didn't differ between the groups. Conclusion: The free vascularized fibula grafting technique had a lesser time to bony union, shorter time for external fixator application, and lower incidence of complications. However, the functional and bony outcomes didn't differ between both techniques. Level of evidence: Level 4.

Evaluation of transpalatal distraction in cleft palate patients.

PURPOSE: The aim of this study was to evaluate the effect of combining a bone-borne palatal expander (distractor) with a maxillary osteotomy in the treatment of narrowed maxillae in treated cleft palate patients. Few articles in the literature isolated the effects of transpalatal distraction in cleft patients and most either excluded cleft patients or grouped them with non-cleft patients. The hypothesis is that the use of a bone-borne palatal expander in conjunction with a maxillary osteotomy would improve the amount of maxillary expansion at the anterior segment with less tipping of the segments and provide a harmonious arch form. METHODS: We studied four patients above 14 years of age with repaired cleft palate and progressive anterior constriction of the arch. All patients received a bone-borne distractor (UNI-Smile Distractor, Titamed, Belgium) combined with a LeFort I level osteotomy without pterygomaxillary disjunction. Dental models and CBCT measurements were used to analyze the skeletal and dental effects of the intervention. RESULT: All the patients who completed the trial had satisfactory expansion and normalization of the maxillary arch form. The average increase in the intercanine distance was 12.9 mm while the average increase in the intermolar distance was 7.2 mm. No significant change in molar inclination or buccal bone thickness was observed. CONCLUSION: The use of bone-borne palatal expanders aided by a maxillary osteotomy (transpalatal distraction) in treated cleft palate patients can provide a harmonious arch form in adolescent and adult patients. This trial was registered in the clinical trials registry with the ID NCT03837652 on February 12, 2019.

Helical distraction is superior to linear and circular distraction in mandibular distraction osteogenesis: an in silico study.

Helical mandibular distraction is theoretically better than linear or circular distraction. However, it is not known whether this more complex treatment will result in unquestionably better outcomes. Therefore, the best attainable outcomes of mandibular distraction osteogenesis were evaluated in silico, given the constraints of linear, circular, and helical motion. This cross-sectional kinematic study included 30 patients with mandibular hypoplasia who had been treated with distraction, or to whom this treatment had been recommended. Demographic information and the computed tomography (CT) scans showing the baseline deformity were collected. The CT scans of each patient were segmented and three-dimensional models of the face created. Then, the ideal distraction outcomes were simulated. Next, the most favorable helical, circular, and linear distraction movements were calculated. Finally, errors were measured: misalignment of key mandibular landmarks, misalignment of the occlusion, and changes in intercondylar distance. Helical distraction produced trivial errors. In contrast, circular and linear distractions resulted in errors that were statistically and clinically significant. Helical distraction also preserved the planned intercondylar distance, while circular and linear distractions led to unwanted changes in the intercondylar distance. It is now evident that helical distraction offers a new strategy to improve the outcomes of mandibular distraction osteogenesis.