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1.  GMP-level adipose stem cells combined with computer-aided manufacturing to reconstruct mandibular ameloblastoma resection defects: Experience with three cases 
Annals of Maxillofacial Surgery  2013;3(2):114-125.
Background:
The current management of large mandibular resection defects involves harvesting of autogenous bone grafts and repeated bending of generic reconstruction plates. However, the major disadvantage of harvesting large autogenous bone grafts is donor site morbidity and the major drawback of repeated reconstruction plate bending is plate fracture and difficulty in reproducing complex facial contours. The aim of this study was to describe reconstruction of three mandibular ameloblastoma resection defects using tissue engineered constructs of beta-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (rhBMP-2), and Good Manufacturing Practice (GMP) level autologous adipose stem cells (ASCs) with progressively increasing usage of computer-aided manufacturing (CAM) technology.
Materials and Methods:
Patients’ three-dimensional (3D) images were used in three consecutive patients to plan and reverse-engineer patient-specific saw guides and reconstruction plates using computer-aided additive manufacturing. Adipose tissue was harvested from the anterior abdominal walls of three patients before resection. ASCs were expanded ex vivo over 3 weeks and seeded onto a β-TCP scaffold with rhBMP-2. Constructs were implanted into patient resection defects together with rapid prototyped reconstruction plates.
Results:
All three cases used one step in situ bone formation without the need for an ectopic bone formation step or vascularized flaps. In two of the three patients, dental implants were placed 10 and 14 months following reconstruction, allowing harvesting of bone cores from the regenerated mandibular defects. Histological examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed.
Discussion:
Constructs with ASCs, β-TCP scaffolds, and rhBMP-2 can be used to reconstruct a variety of large mandibular defects, together with rapid prototyped reconstruction hardware which supports placement of dental implants.
doi:10.4103/2231-0746.119216
PMCID: PMC3814659  PMID: 24205470
Adipose-derived stem cells; beta-tricalcium phosphate; bone morphogenetic protein; computer-aided design
2.  BONE REGENERATION AND DOCKING SITE HEALING AFTER BONE TRANSPORT DISTRACTION OSTEOGENESIS IN THE CANINE MANDIBLE 
Purpose
Bone transport distraction osteogenesis (BTDO) provides a promising alternative to traditional grafting techniques. However, existing BTDO devices have many limitations. The purpose of this research was to test a new device, the mandibular bone transport reconstruction plate (BTRP), in an animal model with comparable mandible size to humans and to histologically and mechanically examine the regenerate bone.
Materials and methods
Eleven adult foxhound dogs were divided into an unreconstructed control group of 5 animals, and an experimental group of 6 animals. In each animal, a 34 mm segmental defect was created in the mandible. The defect was reconstructed with BTRP. Histological and biomechanical characteristics of the regenerate and un-repaired defect were analyzed and compared to bone on the contralateral side of the mandible after 4 weeks of consolidation.
Results
The reconstructed defect was bridged with new bone, with little bone in the control defect. Regenerate density and microhardness were 22.3% and 42.6% lower than the contralateral normal bone, respectively. Likewise, the anisotropy of the experimental group was statistically lower than in the contralateral bone. Half the experimental animals showed non-union at the docking site.
Conclusion
The device was very stable and easy to install and activate. After one month of consolidation, the defect has been bridged with new bone with evidence of active bone formation. Regenerate bone was less mature than the control bone. Studies are underway to identify when the regenerate properties compare to normal bone, and to identify methods to augment bone union at the docking site.
doi:10.1016/j.joms.2011.02.016
PMCID: PMC3181270  PMID: 21601342
Bone transport distraction osteogenesis; microhardness; ultrasound velocity testing; regenerate; bone; mandibular reconstruction; distraction osteogenesis
3.  Skin paddle vascularity of free fibula flap – A study of 386 cases and a classification based on contribution from axial vessels of the leg 
Objective:
The skin paddle of the free fibula flap receives its vascular supply from septocutaneous perforators, musculocutaneous perforators or from both, and these perforators might originate from the peroneal or posterior tibial vessels or from both. The objective of this study was to classify the skin paddles based on the dominance of vascular contribution by these axial vessels through their different perforator systems.
Materials and Methods:
A retrospective analysis of 5-year data of 386 free fibula flaps used in oro-mandibular reconstruction was done and the skin paddle vascularity was studied. While majority of the skin paddles received their blood supply from the peroneal septocutaneous perforators, a few had their dominant supply from the soleus musculocutaneous perforators in addition to peroneal septocutaneous perforators. In few cases, the soleus musculocutaneous perforators were the sole source of blood supply to the skin paddle. The limitation in this study was the inability to augment the clinical observation with cadaveric study.
Results:
The skin paddle of the free fibula flap was classified into four different types (a–d) based on the dominance of vascular contribution by axial vessels of the leg.
Conclusion:
The skin paddle of the free fibula flap has reliable blood supply, but a thorough knowledge of the variations in vascular pattern of the skin paddle is required especially to salvage the larger paddles used in the reconstruction complex oro-mandibular defects.
doi:10.4103/0970-0358.96586
PMCID: PMC3385400  PMID: 22754154
Free fibula flap; musculocutaneous perforators; septo cutaneous perforators; skin paddle; vascular supply
4.  Pre-operative planning for mandibular reconstruction - A full digital planning workflow resulting in a patient specific reconstruction 
Head & Neck Oncology  2011;3:45.
Objectives
Reconstruction of large mandiblular defects following ablative oncologic surgery could be done by using vascularized bone transfer or, more often, primarily with simultaneous or delayed bone grafting, using load bearing reconstruction plates. Bending of these reconstruction plates is typically directed along the outer contour of the original mandible. Simultaneously or in a second operation vascularized or non-vascularized bone is fixed to the reconstruction plate. However, the prosthodontic-driven backward planning to ease bony reconstruction of the mandible in terms of dental rehabilitation using implant-retained overdentures might be an eligible solution. The purpose of this work was to develop, establish and clinically evaluate a novel 3D planning procedure for mandibular reconstruction.
Materials and methods
Three patients with tumors involving the mandible, which included squamous cell carcinoma in the floor of the mouth and keratocystic odontogenic tumor, were treated surgically by hemimandibulectomy.
Results
In primary alloplastic mandible reconstruction, shape and size of the reconstruction plate could be predefined and prebent prior to surgery.
Clinical relevance
This study provides modern treatment strategies for mandibular reconstruction.
doi:10.1186/1758-3284-3-45
PMCID: PMC3195208  PMID: 21968330
Mandibular reconstruction; backward planning; patient specific implant; computer-assisted surgery
5.  “Transport Distraction Osteogenesis for Reconstruction of Mandibular Defects”: Our Experience 
Introduction
Mandibular defects usually involve a combination of osseous and soft tissue deficiency and are among the most challenging problems in maxillofacial surgery, many options are available for mandibular reconstruction. One of the options discussed in literature recently being distraction osteogenesis.
Aim and Objective
The aims and objectives of the study were to evaluate clinically the technique of distraction osteogenesis to reconstruct mandibular defects, using indigenous transport distractors, and to evaluate the efficacy of Indigenous transport distraction osteogenesis device.
Materials and Methods
A prospective, experimental study was designed to examine the use of transport distraction osteogenesis in the treatment of defects of the mandible. Four patients with defects of the mandible were subjected to distraction osteogenesis with indigenously manufactured distraction device. The regenerate was assessed clinically and radiographically.
Results
The results showed that the regenerate was clinically as hard as the adjacent unaffected mandible and radiologic evidence of bone regeneration was observed. The major advantage being regeneration of hard tissue and soft tissue components without the morbidity of donor site, so that functional rehabilitation of the patient is possible.
Conclusion
Thus from our study it is shown that transport distraction osteogenesis using indigenous distractors is a reliable yet affordable option for reconstruction of mandibular defects.
doi:10.1007/s12663-011-0190-4
PMCID: PMC3177527  PMID: 22654358
Distraction osteogenesis; Mandible; Reconstruction; Transport
6.  Reconstruction of mandibular defects - clinical retrospective research over a 10-year period - 
Head & Neck Oncology  2011;3:23.
Backround
Functional and cosmetic defects in the maxillofacial region are caused by various ailments and these defects are addressed according to their need. Simplicity of procedure, intact facial function and esthetic outcome with the least possible donor site morbidity are the minimum requirements of a good reconstruction. Oro-mandibular reconstruction, although a challenge for the head and neck reconstructive surgeon, is now reliable and highly successful with excellent long-term functional and aesthetic outcomes with the use of autogenous bone grafts. Reconstruction of trauma- or mandibular oncologic defects with bony free flaps is considered the gold standard. However the the optimal reconstruction of mandibular defects is still controversial in regards to reconstructive options which include the donor site selection and the timing of surgery. The purpose of this study was to determine the outcome of different osseous reconstruction options using autogenous bone grafts for mandibular reconstructions.
Methods
This study was carried out on 178 patients with mandibular bone defects. They were reconstructed with autogenous bone grafts from different donor sites. At post operative visits they were evaluated for functional and cosmetic results.
Results
The success rate found in this study was around 90%. Only 7.6% of the cases showed poor results regarding facial contours and mouth opening. All other patients were satisfied with their cosmesis and mouth opening at the recipient sites was in the normal range during last follow-up visits. Donor sites were primarily closed in all cases and there was no hypertrophic scar.
Conclusion
Based on this study, autogenous bone grafts are a reliable treatment modality for the reconstruction of mandibular bone defects with predictable aesthetic and functional outcomes. As the free vascularized fibular flap has the least resorption and failure rate, it should be the first choice for most cases of mandiblular reconstruction.
doi:10.1186/1758-3284-3-23
PMCID: PMC3098818  PMID: 21527038
7.  Bifocal Distraction to Regenerate Segmental Mandibular Defects Using a Custom Made Device: A Report of Two Cases 
Background and objective: Mandibular reconstruction following tumor ablative surgery had been a challenge. It has gone through days of temporary stabilization with k-wire, stainless steel reconstruction plate to avascularized and vascularized bone grafts with varying degree of success and failure. Reconstruction with vascularized bone grafts, though most definitive, requires special expertise, expensive equipment, and long operative time. It also produces donor site morbidity and requires a significant learning curve. With the development of transport distraction techniques there has been a paradigm shift from “reconstructive” to “regenerative” surgery. The objective of this study was to identify the feasibility of an internal device for reconstruction of extensive mandibular defects. Methods and material: This article is to highlight a process of attempted mandibular regeneration in two cases using an indigenously designed distractor device. In individuals with extensive post ablative mandibular defects who were unwilling to have a secondary surgical site or were medically unfit for a long reconstructive procedure, the distraction technique can be used to reconstruct the lost mandibular structures. Conclusion: A satisfactory amount of regenerate was achieved using a bifocal distraction osteogenesis technique for extensive defects of the mandible. The custom made device which was used for this purpose was moderately satisfactory and requires further evaluation and refinement.
doi:10.1055/s-0030-1254382
PMCID: PMC3052676  PMID: 22110823
Transport distraction; extensive mandibular defects; single unit distractor device; mandibular reconstruction
8.  The accuracy of computer-assisted primary mandibular reconstruction with vascularized bone flaps: iliac crest bone flap versus osteomyocutaneous fibula flap 
Background
The intention of mandibular reconstruction is to restore the complex anatomy with maximum possible functionality and high accuracy. The aim of this study was to evaluate the accuracy of computer-assisted surgery in primary mandibular reconstruction with an iliac crest bone flap compared with an osteomyocutaneous fibula flap.
Materials and methods
Preoperative computed tomography data of the mandible and the iliac crest or fibula donor site were imported into a specific surgical planning software program. Surgical guides were manufactured using a rapid prototyping technique for translating the virtual plan, including information on the transplant dimensions and shape, into real-time surgery. Using postoperative computed tomography scans and an automatic surface-comparison algorithm, the actual postoperative situation was compared with the preoperative virtual simulation.
Results
The actual flap position showed a mean difference from the virtual plan of 2.43 mm (standard deviation [SD] ±1.26) and a surface deviation of 39% <2 mm and 15% <1 mm for the iliac crest bone flap, and a mean difference of 2.18 mm (SD ±1.93) and a surface deviation of 60% <2 mm and 37% <1 mm for the osteomyocutaneous fibula flap. The position of the neomandible reconstructed with an osteomyocutaneous fibula flap indicated a mean difference from the virtual plan of 1.25 mm (SD ±1.31) and a surface deviation of 82% <2 mm and 57% <1 mm, in contrast to a mean difference of 1.68 mm (SD ±1.25) and a surface deviation of 63% <2 mm and 38% <1 mm for the neomandible after reconstruction with an iliac crest bone flap. For shape analysis, a similarly high accuracy could be calculated for both flaps.
Conclusion
Virtual surgical planning is an effective method for mandibular reconstruction with vascularized bone flaps, and can help to restore the anatomy of the mandible with high accuracy in position and shape. It seems that primary mandibular reconstruction with the osteomyocutaneous fibula flap is more accurate compared with the vascularized iliac crest bone flap.
doi:10.2147/MDER.S62698
PMCID: PMC4064953  PMID: 24966700
computer-assisted surgery; virtual planning; vascularized bone flaps; surgical guide; primary mandibular reconstruction
9.  Mandibular Repair in Rats with Premineralized Silk Scaffolds and BMP-2-modified bMSCs 
Biomaterials  2009;30(27):4522-4532.
Premineralized silk fibroin protein scaffolds (mSS) were prepared to combine the osteoconductive properties of biological apatite with aqueous-derived silk scaffold (SS) as a composite scaffold for bone regeneration. The aim of present study was to evaluate the effect of premineralized silk scaffolds combined with bone morphogenetic protein-2 (BMP-2) modified bone marrow stromal cells (bMSCs) to repair mandibular bony defects in a rat model. bMSCs were expanded and transduced with adenovirus AdBMP-2, AdLacZ gene in vitro. These genetically modified bMSCs were then combined with premineralized silk scaffolds to form tissue engineered bone. Mandibular repairs with AdBMP-2 transduced bMSCs/mSS constructs were compared with those treated with AdLacZ transduced bMSCs/mSS constructs, native (nontransduced) bMSCs/mSS constructs and mSS alone. Eight weeks post-operation, the mandibles were explanted and evaluated by radiographic observation, micro-CT, histological analysis and immunohistochemistry. The presence of BMP-2 gene enhanced tissue engineered bone in terms of the most new bone formed and the highest local bone mineral densities (BMD) found. These results demonstrated that premineralized silk scaffold could serve as a potential substrate for bMSCs to construct tissue engineered bone for mandibular bony defects. BMP-2 gene therapy and tissue engineering techniques could be used in mandibular repair and bone regeneration.
doi:10.1016/j.biomaterials.2009.05.021
PMCID: PMC2871698  PMID: 19501905
10.  Stabilization of Mobile Mandibular Segments in Mandibular Reconstruction: Use of Spanning Reconstruction Plate 
The fibular free flap is the gold standard for mandibular reconstruction. Accurate 3-dimensional contouring and precise alignment of the fibula is critical for reestablishing native occlusion and facial symmetry. Following segmental mandibulectomy, the remaining mandibular fragments become freely mobile. Various stabilization methods including external fixation, intermaxillary fixation, and preplating with reconstruction plate have been used. We describe a modification to the preplating technique. After wide resection of buccal squamous cell carcinoma, our patient had an 11-cm mandibular defect from the angle of the left mandible to the right midparasymphyseal region. A single 2.0-mm Unilock® (Synthes, Singapore) plate was used to span the defect. This was placed on the vestibular aspect of the superior border of the mandibular remnants before resection. Segmental mandibulectomy was then performed with the plate removed. The spanning plate was then reattached to provide rigid fixation. The fibular bone was contoured with a single osteotomy and reattached. The conventional technique involves molding of the plate at the inferior border of the mandible. This is time-consuming and not possible in patients with distorted mandibular contour. It is also difficult to fit the osteotomized fibula to the contoured plate. In comparison, the superiorly positioned spanning plate achieve rigid fixation of the mandible while leaving the defect completely free and unhampered by hardware, allowing space for planning osteotomies and easier fixation of the neomandible. Using this modified technique, we are able to recreate the original mandibular profile with ease.
doi:10.1055/s-0032-1313354
PMCID: PMC3578648  PMID: 23997856
mandibular reconstruction; preplating technique; spanning reconstruction plate
11.  The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible 
The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.
doi:10.1186/1748-717X-7-151
PMCID: PMC3494577  PMID: 22958832
12.  Stem Cells from Deciduous Tooth Repair Mandibular Defect in Swine 
Journal of dental research  2009;88(3):249-254.
Stem cells from human exfoliated deciduous teeth have been identified as a new post-natal stem cell population with multipotential differentiation capabilities, including regeneration of mineralized tissues in vivo. To examine the efficacy of utilizing these stem cells in regenerating orofacial bone defects, we isolated stem cells from miniature pig deciduous teeth and engrafted the critical-size bone defects generated in swine mandible models. Our results indicated that stem cells from miniature pig deciduous teeth, an autologous and easily accessible stem cell source, were able to engraft and regenerate bone to repair critical-size mandibular defects at 6 months post-surgical reconstruction. This pre-clinical study in a large-animal model, specifically swine, allows for testing of a stem cells/scaffold construct in the restoration of orofacial skeletal defects and provides rapid translation of stem-cell-based therapy in orofacial reconstruction in human clinical trials.
doi:10.1177/0022034509333804
PMCID: PMC2829885  PMID: 19329459
deciduous tooth; stem cell; bone; tissue engineering; miniature pig
13.  Stem Cells from Deciduous Tooth Repair Mandibular Defect in Swine 
Journal of Dental Research  2009;88(3):249-254.
Stem cells from human exfoliated deciduous teeth have been identified as a new post-natal stem cell population with multipotential differentiation capabilities, including regeneration of mineralized tissues in vivo. To examine the efficacy of utilizing these stem cells in regenerating orofacial bone defects, we isolated stem cells from miniature pig deciduous teeth and engrafted the critical-size bone defects generated in swine mandible models. Our results indicated that stem cells from miniature pig deciduous teeth, an autologous and easily accessible stem cell source, were able to engraft and regenerate bone to repair critical-size mandibular defects at 6 months post-surgical reconstruction. This pre-clinical study in a large-animal model, specifically swine, allows for testing of a stem cells/scaffold construct in the restoration of orofacial skeletal defects and provides rapid translation of stem-cell-based therapy in orofacial reconstruction in human clinical trials.
doi:10.1177/0022034509333804
PMCID: PMC2829885  PMID: 19329459
deciduous tooth; stem cell; bone; tissue engineering; miniature pig
14.  Use of Recombinant Bone Morphogenetic Protein 2 in Free Flap Reconstruction for Osteonecrosis of the Mandible 
Purpose:
Osteoradionecrosis of the mandible is a debilitating consequence of radiation therapy for head-and-neck malignancy. It can result in pain, bone exposure, fistula formation, and pathologic fracture. Recombinant human bone morphogenetic protein 2 (rhBMP-2) has shown promise in reconstruction of bone defects. The purpose of this study is to determine whether the addition of rhBMP-2 at the union of vascularized bone and native bone improves surgical outcomes in patients with osteonecrosis of the mandible.
Materials and Methods:
This study was a retrospective analysis of patients who were treated between 2006 and 2010 for osteonecrosis of the mandible. Patients requiring definitive reconstruction after failure of a course of conservative management were included. Patients were divided into 2 cohorts depending on whether rhBMP-2 was used during the reconstruction. The primary outcome measure was defined as stable mandibular union.
Results:
Seventeen patients were included. The development of malunion was similar in both groups (13% for rhBMP-2 group vs 11% for non–rhBMP-2 group). Infectious complications were similar between the groups (25% in rhBMP-2 group vs 56% in non–rhBMP-2 group, P = .33). The rates of hardware removal were similar for the 2 groups (33% in non–rhBMP-2 group vs 25% in rhBMP-2 group, P = .10). No cancer recurrences were observed in patients receiving rhBMP-2.
Conclusions:
The use of rhBMP-2 is safe in free flap reconstruction of the mandible, but its ability to significantly improve patient outcomes, as measured by rates of malunion, reoperation, or infection, is still unknown.
doi:10.1016/j.joms.2011.08.037
PMCID: PMC3951353  PMID: 22177824
15.  Apatite-coated Silk Fibroin Scaffolds to Healing Mandibular Border Defects in Canines 
Bone  2009;45(3):517-527.
Tissue engineering has become a new approach for repairing bony defects. Highly porous osteoconductive scaffolds perform the important role for the success of bone regeneration. By biomimetic strategy, apatite-coated porous biomaterial based on silk fibroin scaffolds (SS) might provide an enhanced osteogenic environment for bone-related outcomes. To assess the effects of apatite-coated silk fibroin (mSS) biomaterials for bone healing as a tissue engineered bony scaffold, we explored a tissue engineered bony graft using mSS seeded with osteogenically induced autologous bone marrow stromal cells (bMSCs) to repair inferior mandibular border defects in a canine model. The results were compared with those treated with bMSCs/SS constructs, mSS alone, SS alone, autologous mandibular grafts and untreated blank defects. According to radiographic and histological examination, new bone formation was observed from 4 weeks post-operation, and the defect site was completely repaired after 12 months for the bMSCs/mSS group. In the bMSCs/SS group, new bone formation was observed with more residual silk scaffold remaining at the center of the defect compared with the bMSCs/mSS group. The engineered bone with bMSCs/mSS achieved satisfactory bone mineral densities (BMD) at 12 months post-operation close to those of normal mandible (p>0.05). The quantities of newly formed bone area for the bMSCs/mSS group was higher than the bMSCs/SS group (p<0.01), but no significant differences were found when compared with the autograft group (p>0.05). In contrast, bony defects remained in the center with undegraded silk fibroin scaffold and fibrous connective tissue, and new bone only formed at the periphery in the groups treated with mSS or SS alone. The results suggested apatite-coated silk fibroin scaffolds combined with bMSCs could be successfully used to repair mandibular critical size border defects and the premineralization of these porous silk fibroin protein scaffolds provided an increased osteoconductive environment for bMSCs to regenerate sufficient new bone tissue.
doi:10.1016/j.bone.2009.05.026
PMCID: PMC2828815  PMID: 19505603
Tissue engineering; Silk; Apatite; Bone marrow stromal cells; Canine
16.  Reconstruction of Mandibular Defects 
Seminars in Plastic Surgery  2010;24(2):188-197.
Defects requiring reconstruction in the mandible are commonly encountered and may result from resection of benign or malignant lesions, trauma, or osteoradionecrosis. Mandibular defects can be classified according to location and extent, as well as involvement of mucosa, skin, and tongue. Vascularized bone flaps, in general, provide the best functional and aesthetic outcome, with the fibula flap remaining the gold standard for mandible reconstruction. In this review, we discuss classification and approach to reconstruction of mandibular defects. We also elaborate upon four commonly used free osteocutaneous flaps, inclusive of fibula, iliac crest, scapula, and radial forearm. Finally, we discuss indications and use of osseointegrated implants as well as recent advances in mandibular reconstruction.
doi:10.1055/s-0030-1255336
PMCID: PMC3324243  PMID: 22550439
Bone flap; condyle; fibular flap; mandible; osseointegrated implant; osteocutaneous flap
17.  Pediatric Mandibular Resection and Reconstruction: Long-Term Results with Autogenous Rib Grafts 
Reconstruction of mandibular defects following tumor resection in infants is a particular challenge. Although autogenous rib grafts have no relevance in the restoration of mandibular bone defects occurring after ablative tumor surgery due to limited bone stock and the availability of other donor areas, they are a useful surgical alternative following tumor surgery in infants. We here report on a 2, 5, 8, and 15-year follow-up of four children who were diagnosed with benign tumors of the mandible with osseous destruction at the age of 4, 6, 15, and 18 months, respectively. Histologic diagnoses were melanotic neuroectodermal tumor (n = 2), hemangioendothelioma of the mandible (n = 1), and ameloblastoma (n = 1). Following continuity resection of the mandible, lateromandibular bone defects were restored using autogenous rib grafts. Both clinical and radiologic follow-up visits were performed for all children to assess growth of the facial skeleton and the mandible. One child was already further reconstructed using bone augmentation at the age of 15 years. Cephalometric measurements on panorex films and three-dimensional computed tomographic scans revealed a slight vertical growth excess and transversal growth inhibition of the reconstructed mandible compared with the nonoperated side. Although further growth of rib grafts is difficult to predict and occlusal disharmony may occur due to physiologic maxillary growth and growth of the unaffected mandible, we believe that autogenous rib grafts can be ideally used for the restoration of mandibular continuity defects in newborns and young children. Clinical follow-up visits on a yearly basis and orthodontic controls are useful for early orthodontic treatment of growth deficits. Further corrective surgery with bone augmentation or osseous distraction is required following completion of growth of the facial skeleton.
doi:10.1055/s-0030-1249371
PMCID: PMC3052664  PMID: 22110815
Mandibular reconstruction; rib graft; facial growth; bone graft; pediatric maxillofacial tumor
18.  Biomechanical characteristics of regenerated cortical bone in the canine mandible 
To test the mechanical properties of regenerate cortical bone created using Mandibular Bone Transport (MBT) distraction, five adult male American foxhound dogs underwent unilateral distraction of the mandible with a novel MBT device placed to linearly repair a 30-35 mm bone defect. The animals were sacrificed 12 weeks after the beginning of the consolidation period. Fourteen cylindrical specimens were taken from the inner (lingual) and outer (buccal) plates of the reconstructed mandible and 21 control specimens were removed from the contralateral aspect of the mandible. The mechanical properties of the 35 cylindrical cortical bone specimens were assessed by using a non-destructive pulse ultrasound technique. Results showed that all of the cortical mechanical properties exhibit higher numerical values on the control side than the MBT regenerate side. In addition, both densities and the elastic moduli in the direction of maximum stiffness of the regenerate cortical bone specimens are higher on the lingual side than the buccal side. Interestingly, there is no statistical difference between elastic modulus (E1 and E2) in orthogonal directions throughout the 35 cortical specimens. The data suggest that the regenerate canine cortical bone is not only heterogeneous, but the elastic mechanical properties tend to approximate transverse isotropy at a tissue level as opposed to control cortical bone that is orthotropic. In addition, the elastic mechanical properties are not only higher on the control side but also in the lingual anatomical position, suggesting a stress shielding effect from the presence of the reconstruction plate.
doi:10.1002/term.347
PMCID: PMC3116951  PMID: 21695796
Ultrasound technique; animal model; bony tissue; bone transport; distraction device; bone healing; jaw mechanics
19.  Study of mandible reconstruction using a fibula flap with application of additive manufacturing technology 
Background
This study aimed to establish surgical guiding techniques for completing mandible lesion resection and reconstruction of the mandible defect area with fibula sections in one surgery by applying additive manufacturing technology, which can reduce the surgical duration and enhance the surgical accuracy and success rate.
Methods
A computer assisted mandible reconstruction planning (CAMRP) program was used to calculate the optimal cutting length and number of fibula pieces and design the fixtures for mandible cutting, registration, and arrangement of the fibula segments. The mandible cutting and registering fixtures were then generated using an additive manufacturing system. The CAMRP calculated the optimal fibula cutting length and number of segments based on the location and length of the defective portion of the mandible. The mandible cutting jig was generated according to the boundary surface of the lesion resection on the mandible STL model. The fibular cutting fixture was based on the length of each segment, and the registered fixture was used to quickly arrange the fibula pieces into the shape of the defect area. In this study, the mandibular lesion was reconstructed using registered fibular sections in one step, and the method is very easy to perform.
Results and conclusion
The application of additive manufacturing technology provided customized models and the cutting fixtures and registered fixtures, which can improve the efficiency of clinical application. This study showed that the cutting fixture helped to rapidly complete lesion resection and fibula cutting, and the registered fixture enabled arrangement of the fibula pieces and allowed completion of the mandible reconstruction in a timely manner. Our method can overcome the disadvantages of traditional surgery, which requires a long and different course of treatment and is liable to cause error. With the help of optimal cutting planning by the CAMRP and the 3D printed mandible resection jig and fibula cutting fixture, this all-in-one process of mandible reconstruction furnishes many benefits in this field by enhancing the accuracy of surgery, shortening the operation duration, reducing the surgical risk, and resulting in a better mandible appearance of the patients after surgery.
doi:10.1186/1475-925X-13-57
PMCID: PMC4094279  PMID: 24885749
Additive manufacturing; Computer-aided engineering; Mandible reconstruction; Rapid manufacturing; Reverse engineering
20.  Assessment and determination of human mandibular and dental arch profiles in subjects with lower third molar impaction in Port Harcourt, Nigeria 
Annals of Maxillofacial Surgery  2011;1(2):126-130.
Aim:
The aim of this study was to determine the normal size of the mandible and the difference in dental arch length and total teeth size space that is necessary to prevent lower third molar impaction.
Background:
The mandible is an important component of facial skeleton and its morphology is relevant to the determination of acceptable aesthetics. In addition, function of the dentition is dependent on the available space for positioning of all the teeth including the third molar, and for enough space to be created, the sizes of the mandible and dental arch must be within normal ranges.
Materials and Methods:
Impaction of the lower third molar was assessed by clinical evaluation and radiography. The total length of the mandible is determined by adding the distance between the midpoint of the tragus and soft tissue around the angle of the mandible to the distance between the angle and the soft tissue in the region of the chin. Mandibular width is the distance between the two angles of the mandible. The teeth sizes of the three anterior teeth, the two premolars, and the two molars were measured with a divider/ruler and recorded. The anterior-posterior distance of the arch from the midline to the retromolar pad was also measured.
Results:
There were 44 (53%) females and 39 (47%) males. Eighty-one (97.6%) of the participants were between 16 and 23 years old, while 2 (2.4%) were in the fourth decade. There were 38 (45.8%) cases of impaction and 45 (54.2%) cases of unimpacted mandibular third molar. The means/standard deviation values for mandibular length for males in each group are 18.20 ± 0.98 and 18.20 ± 1.13 cm, respectively. The values for mandibular length for females in each group are 17.20 ± 0.76 and 17.60 ± 1.07. There are significant differences between the genders for mandibular length (P < 0.05, 95% CI). The means/standard deviation values for mandibular width for both genders in each group are also shown. There are also significant differences between the genders for mandibular width (P < 0.05, 95% CI). Normal sized mandible should have a length within or above 17.22–19.33 cm in males and 16.44–18.67 cm in females, while normal dental arch-total teeth size difference range should be within or above 0.71–1.20 cm in males and 0.76–1.10 cm in females in order to accommodate a properly erupting third molar.
Conclusions:
Based on these figures, clinicians may be justified to perform a preventive or therapeutic surgical removal of the impacted lower third molars of the postpubertal patients whose parameters fall below these set values. This study is also useful for evaluation of patients who would need orthognathic and reconstructive surgeries.
doi:10.4103/2231-0746.92775
PMCID: PMC3591016  PMID: 23482900
Dental arch; impaction; mandible; third molar
21.  Development of 3D statistical mandible models for cephalometric measurements 
Imaging Science in Dentistry  2012;42(3):175-182.
Purpose
The aim of this study was to provide sex-matched three-dimensional (3D) statistical shape models of the mandible, which would provide cephalometric parameters for 3D treatment planning and cephalometric measurements in orthognathic surgery.
Materials and Methods
The subjects used to create the 3D shape models of the mandible included 23 males and 23 females. The mandibles were segmented semi-automatically from 3D facial CT images. Each individual mandible shape was reconstructed as a 3D surface model, which was parameterized to establish correspondence between different individual surfaces. The principal component analysis (PCA) applied to all mandible shapes produced a mean model and characteristic models of variation. The cephalometric parameters were measured directly from the mean models to evaluate the 3D shape models. The means of the measured parameters were compared with those from other conventional studies. The male and female 3D statistical mean models were developed from 23 individual mandibles, respectively.
Results
The male and female characteristic shapes of variation produced by PCA showed a large variability included in the individual mandibles. The cephalometric measurements from the developed models were very close to those from some conventional studies.
Conclusion
We described the construction of 3D mandibular shape models and presented the application of the 3D mandibular template in cephalometric measurements. Optimal reference models determined from variations produced by PCA could be used for craniofacial patients with various types of skeletal shape.
doi:10.5624/isd.2012.42.3.175
PMCID: PMC3465760  PMID: 23071968
Three-Dimensional Image; Mandible; Cephalometry; Principal Component Analysis
22.  The Nature and Role of Periosteum in Bone and Cartilage Regeneration 
Cells, Tissues, Organs  2011;194(2-4):320-325.
This study was undertaken to determine whether periosteum from different bone sources in a donor results in the same formation of bone and cartilage. In this case, periosteum obtained from the cranium and mandible (examples of tissue supporting intramembranous ossification) and the radius and ilium (examples of tissues supporting endochondral ossification) of individual calves was used to produce tissue-engineered constructs that were implanted in nude mice and then retrieved after 10 and 20 weeks. Specimens were compared in terms of their osteogenic and chondrogenic potential by radiography, histology, and gene expression levels. By 10 weeks of implantation and more so by 20 weeks, constructs with cranial periosteum had developed to the greatest extent, followed in order by ilium, radius, and mandible periosteum. All constructs, particularly with cranial tissue although minimally with mandibular periosteum, had mineralized by 10 weeks on radiography and stained for proteoglycans with safranin-O red (cranial tissue most intensely and mandibular tissue least intensely). Gene expression of type I collagen, type II collagen, runx2, and bone sialoprotein (BSP) was detectable on QRT-PCR for all specimens at 10 and 20 weeks. By 20 weeks, the relative gene levels were: type I collagen, ilium >> radial ≥ cranial ≥ mandibular; type II collagen, radial > ilium > cranial ≥ mandibular; runx2, cranial >>> radial > mandibular ≥ ilium; and BSP, ilium ≥ radial > cranial > mandibular. These data demonstrate that the osteogenic and chondrogenic capacity of the various constructs is not identical and depends on the periosteal source regardless of intramembranous or endochondral ossification. Based on these results, cranial and mandibular periosteal tissues appear to enhance bone formation most and least prominently, respectively. The appropriate periosteal choice for bone and cartilage tissue engineering and regeneration should be a function of its immediate application as well as other factors besides growth rate.
doi:10.1159/000324642
PMCID: PMC3178095  PMID: 21597269
Periosteum; Bone; Cartilage; Regeneration; Tissue engineering
23.  Measures of health-related quality of life and socio-cultural aspects in young patients who after mandible primary reconstruction with free fibula flap 
Background
The reconstruction of mandibular defects after trauma or tumor resection is one of the most challenging problems facing reconstructive surgeons. Although the primary intended outcome of surgery to treat head-and-neck malignancies is still the disease-free survival of the patient, health-related quality of life (HRQOL) is now seen as an essential secondary outcome. This study aims to evaluate HRQOL outcomes in young patients undergoing primary mandible reconstruction with free fibula flap and to collect information about their socio-cultural situation.
Methods
The HRQOL outcomes of 25 young patients after primary mandible reconstruction with free fibula flap for mandible malignancies were assessed using the Medical Outcomes Study-Short Form-36 (MOS SF-36) and University of Washington Quality of Life (UW-QOL) questionnaires 12 months postoperatively.
Results
Using the UW-QOL questionnaire, the best-scoring domain was ‘pain’, whereas ‘chewing’ and ‘anxiety’ were given the lowest scores. Using the MOS SF-36 questionnaire, the best-scoring domain was ‘physical functioning’, while ‘bodily pain’ and ‘general health’ also scored well.
Conclusions
Mandible reconstruction with fibula flap will significantly influence a young patient’s HRQOL. Young patients pay more attention to postoperative facial appearance; this should be considered in surgical planning. The socio-cultural data show a fairly low level of education for the majority of patients.
doi:10.1186/1477-7819-11-250
PMCID: PMC3850790  PMID: 24083617
Free fibula flap; Health-related quality of life; Reconstruction
24.  Three-Dimensional Evaluation of Mandibular Bone Regenerated By Bone Transport Distraction Osteogenesis 
Calcified tissue international  2011;89(1):43-52.
The purpose of this study was to evaluate the structure and material properties of native mandibular bone and those of early regenerate bone, produced by bone transport distraction osteogenesis. Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 3- to 4-cm defect was created on one side of the mandible. A bone transport reconstruction plate, consisting of a reconstruction plate with an attached intraoral transport unit, was utilized to stabilize the mandible and regenerate bone at a rate of 1 mm/day. After the distraction period was finished, the animals were killed at 6 and 12 weeks of consolidation. Micro-computed tomography was used to assess the morphometric and structural indices of regenerate bone and matching bone from the unoperated contralateral side. Significant new bone was formed within the defect in the 6- and 12-week groups. Significant differences (P ≤ 0.05) between mandibular regenerated and native bone were found in regard to bone volume fraction, mineral density, bone surface ratio, trabecular thickness, trabecular separation, and connectivity density, which increased from 12 to 18 weeks of consolidation. We showed that regenerated bone is still mineralizing and that native bone appears denser because of a thick outer layer of cortical bone that is not yet formed in the regenerate. However, the regenerate showed a significantly higher number of thicker trabeculae.
doi:10.1007/s00223-011-9492-2
PMCID: PMC3133632  PMID: 21556698
Micro-computed tomography; Distraction device; Bone transport; Bone regeneration
25.  Analysis of the Biomechanical Properties of the Mandible After Unilateral Distraction Osteogenesis 
Plastic and Reconstructive Surgery  2010;126(2):533-542.
Background
The purpose of this study was to establish biomechanical outcomes measures to evaluate how mandibular distraction osteogenesis affects the overall quality of bone healing in the mandible. Strength and functional integrity of the regenerate was quantitatively determined after unilateral mandibular distraction osteogenesis in comparison to the contralateral mandible, and a partially reduced fracture. We hypothesized that the breaking load, yield and stiffness of mandibular distraction osteogenesis would be significantly reduced in comparison to both the contralateral mandible and a partially reduced fracture.
Methods
Sprague-Dawley rats underwent mandibular distraction osteogenesis (n=8) or a partially reduced fracture (n=6). External fixators were secured, unilateral osteotomies created behind the 3rd molar, followed by either mandibular distraction osteogenesis: 4days latency then 0.3mm Q12hrs × 8days (5.1mm) or a partially reduced mandibular fracture: fixed gap post-operatively (2.1mm). Both groups underwent 4 weeks consolidation. The contralateral mandibles were used as controls (n = 14). Mandibles were tension tested at 0.5mm/s to failure and then breaking load, yield and stiffness were determined.
Results
mandibular distraction osteogenesis had significantly lower breaking load, yield and stiffness when compared to the contralateral mandible, by 40%, 30% and 60%, respectively. Breaking load was reduced in partially reduced mandibular fractures by 40% when compared to mandibular distraction osteogenesis.
Conclusion
Utilizing a standard Ilizarov protocol, the strength and durability of the regenerate, as measured by breaking load, yield and stiffness in mandibular distraction osteogenesis was significantly lower than contralateral mandibles. Surprisingly, the breaking load of mandibular distraction osteogenesis was significantly greater than partially reduced mandibular fracture. These verifiable metrics of regenerate integrity can be utilized to discern optimal outcomes of mandibular distraction osteogenesis, and to extrapolate the data from the bench and bring it to the bedside, enhancing the clinical applications of this powerful technique.
doi:10.1097/PRS.0b013e3181de2240
PMCID: PMC3401944  PMID: 20375764

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