Proximal Redundant Fibula Bone Template for Flap Osteotomies in Mandibular Reconstruction: A Novel Technique.

Background: Free fibula flap has been the workhouse of reconstruction for segmental mandibular defects. The use of computer aided design helps in achieving the desired aesthetic and functional outcome. It has its advantages but it comes with an extensive financial burden. Purpose: We propose the use of redundant proximal fibula bone segment as a template and a cutting guide for flap osteotomies in mandibular reconstruction. Methods: We have used this surgical technique in a case of T4 oral cancer that required segmental mandibulectomy. Result: Average ischaemia time was 1 hour and 30 minutes. Based on histopathology report, both the patients required adjuvant radiotherapy. Oral competence was maintained in both the patients. Post-operatively, the contour and the orientation of the mandibular reconstruction were comparable both clinically and radiologically to the previously planned 3D cases. Conclusion: This surgical technique provides an accurate guide for end angle osteotomy. In addition, it does not require any extra surgical step and does not increase the ischemia time of the flap with no additional extra cost. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01567-4.

Small Extracellular Vesicles Laden Oxygen-Releasing Thermosensitive Hydrogel for Enhanced Antibacterial Therapy against Anaerobe-Induced Periodontitis Alveolar Bone Defect.

Periodontitis is a bacterially induced chronic destructive inflammatory disease that leads to irreversible destruction of the tooth supporting structure, including connective tissue destruction, bone resorption, and even tooth loss. Until now, there has been no effective treatment to repair inflammatory bone loss in periodontitis. Recently, small extracellular vesicles (sEVs) emerged as the essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. However, limitations of antimicrobial activity associated with the use of sEVs have led to the urgency of new alternative strategies. Currently, we investigated the potential of a biocompatible oxygen-releasing thermosensitive hydrogel laded with sEVs secreted by bone marrow MSCs (BMMSCs) for the alveolar bone defect in periodontitis. The hydrogel composed of different polymers such as chitosan (CS), poloxamer 407 (P407), and cross-linked hyaluronic acid (c-HA) conglomerating is a kind of nanoporous structure material. Then, the gel matrix further encapsulated sEVs and calcium peroxide nanoparticles to realize the control of sEVs and oxygen release. Furthermore, ascorbic acid was added to achieve the REDOX equilibrium and acid-base equilibrium. The experiments in vivo and in vitro proved its good biocompatibility and effectively inhibited the growth of the periodontal main anaerobe, relieved periodontal pocket anaerobic infections, and promoted the periodontal defect regeneration. Therefore, this finding demonstrated that it was a promising approach for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria-induced infections, for future clinical application.

Bilateral double site (calvarial and mandibular) critical-size bone defect model in rabbits for evaluation of a craniofacial tissue engineering constructs.

Most existing preclinical models for evaluating the biosafety and bone-regeneration efficacy of innovative bone substitute materials (BSMs) or tissue engineering (TE) constructs only consisted of a single-site defect and the anatomical locations of defect varied drastically. While the compelling evidence showed that the bone healing pattern is location-dependent, owing to developmental, structural, and functional differences of anatomical locations, this is particularly true for the craniofacial region. Taking this into account, the bone healing efficiency of a BSM shown at one anatomical defect location cannot ensure the same impact at another. This prompted us to develop, for the first time, a model of bilateral critical-sized defect (CSD) at two distinctly different locations (non-load-bearing parietal calvaria and load-bearing mandibular body) co-existing in one rabbit to reduce the number of animals needed and avoid the influence of interindividual variability and evaluation bias on comparisons. 24 healthy adult male New Zealand White rabbits were randomly assigned to a group, either control, autograft (considered the "gold standard") or a clinically relevant BSM (biphasic calcium phosphate granules) (BCPg, Mastergraft®, Medronics). The full-thickness cylindrical calvarial defect (ø10 mm) on frontoparietal region and mandibular composite defect (ø11 mm) on the body of the mandible were created bilaterally using low-speed drilling with saline irrigation. The defect on one side was filled with autograft debris or BCPg, and the other side was no graft (empty). Following the euthanasia of animals at the predetermined intervals (4w and 12w), the defect zones were examined macroscopically and then sampled and processed for microcomputed tomography (microCT) and histological analysis. All surgeries went uneventfully, and all rabbits recovered slowly but steadily. No symptoms of infection or inflammation associated with the defect were observed during the experiment. At 4w and 12w, macroscopic views of all defect sites were clean without any signs of necrosis or abscess, and no intraoral communication was found. The analysis of microCT and histological findings showed the non-healing nature of the empty defect, thereby both calvaria and mandible CSDs can be validated. The study of the application of BCPg in this defect model highlighted good osteointegration and excellent osteoconductive properties but compromised the osteoinductive properties of this material (compared with autograft). To conclude, this novel double-site CSD model holds great promise in the application for preclinical evaluation of BSMs, TE construct, etc. With a reduced number of animals in use, and lower interindividual variability and evaluation bias for comparisons.

Association between non-vascularised bone graft failure and compartment of the defect in mandibular reconstruction: a systematic review and meta-analysis.

Controversy exists regarding the influence of the graft placement site in the mandible on the success of non-vascularised bone grafts. In this study, we examine the association between the compartment of the mandibular defect and the bone graft failure rate. A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Failure rates according to the compartment of mandibular defect were extracted and analysed by meta-analysis. The Newcastle-Ottawa Scale was used to assess the quality of the studies, and publication bias was evaluated using funnel plots. The search strategy identified 27 publications. After screening, five were selected for review. Based on the result of comparison among these five, we found no significant statistical association between the bone graft failure rate and compartment of mandibular defect, although further investigation of prospective randomised cohort studies is required.

Rabbit calvarial and mandibular critical-sized bone defects as an experimental model for the evaluation of craniofacial bone tissue regeneration.

INTRODUCTION: Many studies have aimed to investigate the regeneration potential of bone substitutes through animal models at different defect sites, where the bone healing mechanism varies due to developmental, structural and functional differences. This study aims to develop a rabbit model with two functionally different (non-load-bearing calvarias and load-bearing mandibular) critical-sized defects (CSD) in one rabbit. MATERIAL & METHOD: The comparison of the "gold standard" autograft to a sham (no graft) control was undertaken in order to validate this model; at the same time, a 3D-printed biphasic calcium phosphate scaffold was implanted to test its utility in the evaluation of new bone substitute materials. Twenty rabbits were selected with both a 10 mm calvaria defect and a 11 mm bicortical semi-cylindrical mandibular defect. The animals were euthanized at 4 and 12 weeks once surgery, microcomputed tomography and histological analysis had been performed. RESULTS: In the case of the calvaria, the results for the non-healing sham group compared with the healing of those that had undergone the autograft validated the CSD model. But the mandibular defect was not validated, due to the particularity of mandible high mechanical stress and infectious risk. DISCUSSION: This study showed for the first time that rabbits have a high tolerance for the bilateral double-site CSD model under consideration; and further studies are essential to modify and improve the design of mandibular CSD.

Vertical mandibular bone augmentation by the osteodistraction of the transplanted fibula free flap: A case series with long-term follow-up.

Vertical augmentation of the mandible to prepare dental implant therapy is still a challenge, especially with large mandible defects. Reconstruction with fibula free flap is a regularly applied approach in such cases, but it does not always yield optimal results: the resulting crestal height might differ significantly from the crestal height of the patient's intact bone, which makes esthetic and functional rehabilitation difficult. Osteodistraction of the integrated flap is a known but rarely discussed approach where the already integrated flap undergoes additional distraction. Through the four cases reported here, we would like to demonstrate that the osteodistraction of the transplanted fibula free flap is a useful and efficient method of secondary augmentation for cases where the flap itself fails to produce the desired crestal height, and no other method is applicable. The cases show that the method allows outcomes that are highly satisfactory, both in the functional and esthetic sense.

Systemic and Local Biocompatibility Assessment of Graphene Composite Dental Materials in Experimental Mandibular Bone Defect.

The main objective of this research is to demonstrate the biocompatibility of two experimental graphene dental materials by in vitro and in vivo tests for applications in dentistry. The novel graphene dental materials, including one restorative composite and one dental cement, were subjected to cytotoxicity and implantation tests by using a rat model of a non-critical mandibular defect. In vitro cytotoxicity induced by materials on human dental follicle stem cells (restorative composite) and dysplastic oral keratinocytes (dental cement) was investigated at 37 °C for 24 h. After in vivo implantation, at 7 weeks, bone samples were harvested and subjected to histological investigations. The plasma biochemistry, oxidative stress, and sub-chronic organ toxicity analysis were also performed. The resulting cytotoxicity tests confirm that the materials had no toxic effects against dental cells after 24 h. Following graphene dental materials implantation, the animals did not present any symptoms of acute toxicity or local inflammation. No alterations were detected in relative organ weights and in correlation with hepatic and renal histological findings. The materials' lack of systemic organ toxicity was confirmed. The outcomes of our study provided further evidence on the graphene dental materials' ability for bone regeneration and biocompatibility.

Three-dimensional modeling of the scapular tip for anterolateral and lateral mandibular defects.

OBJECTIVE: Three-dimensional (3D) computational modeling represents an invaluable surgical tool for complex reconstructive cases. There exists limited data on 3D imaging to evaluate the use of the scapular tip free flap in complex, anterolateral mandibular reconstructions. The purpose of this study is to radiographically assess the scapular tip free flap in anterolateral defects of the mandible. METHODS: A retrospective case series of 50 patients was performed on head and neck cancer patients treated at Michigan Medicine from 2013 to 2018. Patients who had pre-operative computed tomography neck and thorax for review were included. RESULTS: The scapular tip was able to cover defects from the ipsilateral mandibular angle to the symphysis in all cases. On average, the bone extended to cover defects from the mandibular angle to 17 mm (SD ± 3.6 mm) beyond the mandibular symphysis, which equates to 70% (95% CI 0.66-0.74) of the distance from the symphysis to the contralateral mental foramen. CONCLUSION: Use of the scapular tip as a donor site for reconstruction of the mandibular body can be evaluated pre-operatively utilizing 3D imaging. All patients were able to achieve posterior coverage to the vertical plane of the mandibular condyle and contralateral extension across the symphysis on average extends almost three-fourths of the distance to the mandibular foramen. The extent of contralateral coverage can be more accurately delineated utilizing the patient's pre-operative imaging.

Acute open callus manipulation: Clinical experience with a new surgical technique for solving old problems in distraction osteogenesis.

BACKGROUND: Transport distraction osteogenesis is challenged as a potential alternative to free-flap reconstruction of segmental jaw defects due to its longer treatment time, vector control difficulties, need for additional bone-grafting, and problems creating a curvilinear shape. We propose a new technique of acute open callus manipulation and fixation (AOCMF), which addresses these challenges. METHODS: A retrospective analysis of all patients with jaw defects who underwent DO and AOCMF between 2006 and 2015 was performed. Clinical and demographic data were recorded and analysed. Representative treated cases were presented. RESULTS: Fourteen adult patients were treated, seven for maxillary and seven for mandibular defects of mixed etiology. The mean length of distraction was 4.9 cm (range 3-8 cm). AOCMF was performed between the first and third week of the consolidation phase. Average treatment time was 7.6 weeks (range 4-13 weeks). Mean follow-up was 38 months (range 25-76 months). Stable curvilinear bone shape and soft tissue coverage was achieved in all patients except one. Four complications were recorded. CONCLUSIONS: AOCMF following DO is a safe and reliable technique for reconstruction of segmental defects. It represents a useful alternative to free-flap reconstruction in selected patients. When compared with traditional bone transport techniques, it allows a decrease in the number of surgical procedures and in average treatment time.

Combined bilobed trapezius myocutaneous and scapula osteomyocutaneous flaps for the restoration of through-and-through defects of the mandible following salvage surgery for recurrent head and neck tumours.

This study was performed to evaluate the outcomes of combined bilobed trapezius myocutaneous and scapula osteomyocutaneous flaps for the restoration of through-and-through defects of the mandible. The subjects were six patients with recurrent malignant tumours who underwent salvage surgeries and reconstruction with combined flaps based on the transverse cervical vessels (TCVs). All patients had combined bone (four type H, one type LCL, and one type C) and extensive soft tissue defects (through-and-through defects) following salvage surgery. All tumours were removed and the complex defects restored successfully. Two patients experienced minor complications: one minor intraoral flap failure and one case of wound dehiscence at the donor site. The appearance of the face and neck was satisfactory or acceptable in all patients. No patient showed severely limited range of motion of the upper limb. The patients were followed up for 10 to 18months. One patient was living with no evidence of disease. The use of combined bilobed trapezius myocutaneous and scapula osteomyocutaneous flaps based on the TCVs may be an effective approach for the restoration of through-and-through defects of the mandible and may provide satisfactory or acceptable functional and aesthetic outcomes following salvage surgery for advanced head and neck tumours.

Micro-computed tomography analysis of early stage bone healing using micro-porous titanium mesh for guided bone regeneration: preliminary experiment in a canine model.

The aim of this study was to evaluate the amount of bone formation beneath a defect area after treatment with titanium mesh membranes with different thicknesses and pore sizes alone or in combination with bone graft to induce bone formation during the early stage of healing time. The mandibular premolars were extracted bilaterally from three adult beagle dogs, and 8-mm-diameter bone defects were created on the buccal site of the premolar regions. Hydroxyapatite bone graft substitute was applied in the defect site unilaterally, and other site was left empty. Then, a novel micro-porous mesh (50 µm in pore diameter) or commercially available macro-porous titanium mesh (1700 µm in pore diameter) was placed on the defect and secured with screws. After 4 weeks, the mandibles were harvested, imaged using micro-computed tomography, and prepared for histological and morphometric evaluation. Higher new bone volumes (mm3), percentage of new bone volumes in the total defect volumes (bone ratio: %), and new bone area (mm2) through morphometric evaluation were found on the novel membranes with 50-µm-diameter pores compared to the commercial titanium mesh. Moreover, experiment sites without bone graft were observed with higher new bone volume and bone ratio compared with sites with bone graft. However, bone mineral density of novel mesh was observed to be lower compared with other experimental sites. Under the experimental condition, the result of this study suggests that titanium meshes with 50-µm-diameter pores were effective for guided bone regeneration in the early stage of healing.

Reconstruction of a Combined Maxillectomy and Segmental Mandibulectomy Defect in a Seven-Year-Old with a Single Free Fibula Osteocutaneous Flap.

Combined upper alveolectomy and segmental mandibulectomy are complex defects. Reconstruction of these defects is usually suboptimal. We describe the case of a pediatric patient with vessel-depleted neck with recurrent vascular malformation involving the ramus and coronoid process of mandible and a previous history of maxillectomy and a reconstruction with anterolateral thigh flap. The patient underwent wide resection. The defects involving the upper alveolus and mandible were simultaneously reconstructed with a single free fibula flap.

Local delivery of recombinant human FGF7 enhances bone formation in rat mandible defects.

Fibroblast growth factor 7 (FGF7) plays an important role in regulating the proliferation, migration, and differentiation of cells. However, the role of FGF7 in bone formation is not yet fully understood. We examined the effect of FGF7 on bone formation using a rat model of mandible defects. Rats underwent mandible defect surgery and then either scaffold treatment alone (control group) or FGF7-impregnated scaffold treatment (FGF7 group). Micro-CT and histological analyses revealed that the FGF7 group exhibited greater bone formation than did the control group 10 weeks after surgery. With the exception of total porosity (%), all bone parameters had higher values in the FGF7 group than in the control group at each follow-up after surgery. The FGF7 group showed greater expression of osteogenic markers, such as runt-related transcription factor 2, osterix, osteocalcin, bone morphogenetic protein 2, osteopontin, and type I collagen in newly formed bone than did the control group. The delivery of FGF7 also increased the messenger RNA expression of stromal-cell-derived factor 1 (SDF-1) and CXCR4 in newly formed bone in the FGF7 group compared with the control group. Further, addition of exogenous FGF7 induced migration of rat bone marrow stromal cells and increased the expression of SDF-1 and CXCR4 in the cells. Furthermore, the addition of FGF7 augmented mineralization in the cells with increased expression of osteogenic markers, and this augmentation was significantly suppressed by an inhibitor specific for c-Jun N-terminal kinase (SP600125) or extracellular-signal-regulated kinase (PD98059). Collectively, these results suggest that local delivery of FGF7 increases bone formation in a mandible defect with enhanced osteogenesis and chemoattraction.

Current concepts of bone tissue engineering for craniofacial bone defect repair.

Craniofacial fractures and bony defects are common causes of morbidity and contribute to increasing health care costs. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. Current methods of repair and reconstruction include rigid fixation, grafting, and free tissue transfer. However, these methods carry innate complications, including plate extrusion, nonunion, graft/flap failure, and donor site morbidity. Recent research efforts have focused on using stem cells and synthetic scaffolds to heal critical-sized bone defects similar to those sustained from traumatic injury or ablative oncologic surgery. Growth factors can be used to augment both osteogenesis and neovascularization across these defects. Many different growth factor delivery techniques and scaffold compositions have been explored yet none have emerged as the universally accepted standard. In this review, we will discuss the recent literature regarding the use of stem cells, growth factors, and synthetic scaffolds as alternative methods of craniofacial fracture repair.