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Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

ABSTRACT: Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.

SUBMITTER: Tatara AM

PROVIDER: S-EPMC6452741 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

Tatara Alexander M AM Koons Gerry L GL Watson Emma E Piepergerdes Trenton C TC Shah Sarita R SR Smith Brandon T BT Shum Jonathan J Melville James C JC Hanna Issa A IA Demian Nagi N Ho Tang T Ratcliffe Anthony A van den Beucken Jeroen J J P JJJP Jansen John A JA Wong Mark E ME Mikos Antonios G AG

Proceedings of the National Academy of Sciences of the United States of America 20190318 14

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry ...[more]

PMID: 30886100

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Project description:BackgroundFree osteocutaneous fibula flap (FFF) is currently considered the best option for segmental mandibular reconstruction; however, there are only a few reports comparing secondary with primary reconstructions using FFF. This study aimed to evaluate the safety and efficacy of secondary mandibular reconstruction using FFF when compared with primary mandibular reconstruction.MethodsFrom October 2018 to February 2020, patients who underwent mandibular reconstruction using FFF after segmental mandibulectomy were retrospectively reviewed. The size and location of the mandibular defect, the segment length and number of osteotomies in the fibula, types of the mandibular plating system, kinds and laterality of the recipient vessels were recorded from the surgical notes. Flap survival, duration of nasogastric tube use, and implant installation after reconstruction were recorded as postoperative evaluation indices.ResultsTwelve patients underwent mandibular reconstruction using FFF during the study period. There were no significant differences in demographic characteristics other than body mass index between the primary (n = 8) and secondary (n = 4) reconstruction groups. No significant differences were observed in the size and location of defects, the segment length and number of osteotomies in the fibula, and the types of mandibular plating system. There was no significant difference in the kinds of recipient vessels; however, the laterality of recipient vessels was ipsilateral in all cases of primary reconstructions and contralateral in all cases of secondary reconstructions. Three out of eight patients with primary FFF reconstruction developed partial flap necrosis. Four patients in the secondary FFF reconstruction group achieved complete flap survival. The duration of use of the nasogastric tube and implant installation after reconstruction was comparable between the two groups.ConclusionSafe and effective secondary mandibular reconstruction can be performed in this clinical case study using FFF.

Project description:INTRODUCTION:Functional and cosmetic defects in maxillofacial region are caused by various ailments like trauma, neoplasm, developmental, infections and iatrogenic causes. Reconstruction of these defects with free flaps remains the gold standard but demerits like need for surgical expertise and equipment, prolonged duration of surgery, compliance of the patient and increased cost are associated with microvascular reconstruction. Hence reconstruction with nonvascular bone grafts can be considered when defect is nonirradiated and <9 cm and with sufficient soft tissue cover available. PURPOSE:To retrospectively evaluate clinical, radiological outcome and complications encountered with mandibular reconstruction using non vascular fibula graft. PATIENTS AND METHODS:This retrospective study included 7 patients who were treated in the Department of Oral and Maxillofacial Surgery, Narayana Dental College and Hospital, Nellore, AP between 2011 and 2013 with histologically proven benign osteolytic lesions of mandible that require a segmental mandibulectomy and primary reconstruction using autogenous non-vascularised fibular graft. The clinical case records of the patients and personal patient assessment forms (Quality of Life Assessment Forms) were analysed. They were recalled every 3rd, 6th and 9th month after surgery for evaluation of clinical, radiological outcome of the graft and complications occurring at recipient and donor sites. RESULTS:In all the 7 patients, the lower border continuity was maintained except in one where the graft was dislodged. Tongue movements in all the patients were unrestricted. Jaw movements were affected in cases of ramus defects with slight deviation to operated side and reduced mouth opening. Radiological observations revealed no significant changes in 3 months except for slight reduction in graft height. The radioopaque bridging with continuity of lower border of mandible was noticed in 6th month indicating the take of the graft. This was achieved in every case except in one where the graft was lost due to dislodged reconstruction plate. In 9th month the edges of the graft i.e., graft to native mandible junction showed more resorption (3 mm) especially where there is >2 mm of gap. Whereas increase in height of graft in other areas especially in graft to graft junction was seen. Significant graft resorption was seen in two cases. There were no major complications associated with the donor site. CONCLUSION:Avascular fibula graft although a second choice to vascularised fibula, is a favourable option for mandible defects of 6-10 cm under optimum conditions especially in developing countries where financial and/or surgical resources are limited. An attempt for primary reconstruction with this is never futile as it prevents aesthetic deformity even in the event of failure and thus makes secondary reconstruction easy. However in order to confirm the results a prospective study with large scale of patients is necessary.

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Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

Publications

Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

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