Reconstruction of large mandibular defects using autologous tissues generated from in vivo bioreactors

Tatara, Alexander M.; Shah, Sarita R.; Demian, Nagi; Ho, Tang; Shum, Jonathan; Beucken, Jeroen J.J.P. van den; Jansen, John A.; Wong, Mark; Mikos, Antonios G.

doi:10.1016/j.actbio.2016.09.013

Cited by 35 publications

(60 citation statements)

References 29 publications

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“…4 A-D, both AG and SG were capable of supporting new viable mineralized tissues. Of note, as described in previous work (5,6), bioreactors initially filled with AG had nonzero measurements of remaining SG in Fig. 4F due to artifact (unbiased thresholding, including cellular debris, detected as remaining SG).…”

Section: Resultssupporting

confidence: 53%

“…To that effect, we and others have investigated in vivo bioreactors for the generation of engineered autologous vascularized bony free flaps (4)(5)(6)(7). These bioreactors are implanted at a site ectopic to the defect, such as against the periosteum of the rib cage.…”

mentioning

confidence: 99%

“…This strategy utilizes acellular scaffolds without the need for exogenous cells or supplemented growth factors. As the tissues grow to fill the size and shape of the bioreactor (5,6), customized vascularized flaps can be designed for specific geometries on a patient-to-patient basis.…”

mentioning

confidence: 99%

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Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Tatara

Koons

Watson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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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.

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Section: Resultssupporting

confidence: 53%

mentioning

confidence: 99%

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Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Tatara

Koons

Watson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…However, reducing or eliminating the need for autologous bone would be a clinical advantage so as to minimize the number of donor sites. Tatara et al selected the rib membrane as a bioreactor to evaluate the effects of autologous bone and synthetic ceramics on the tissue produced and to reconstruct a mandibular defect using bioreactors filled with a synthetic graft as either avascular grafts or vascularized flaps. The scaffold used was either a morcellized autograft, synthetic graft, or a 50/50 (v/v) mixture of the two.…”

Section: Pre‐vascularization Of a Scaffoldmentioning

confidence: 99%

Section: Pre‐vascularization Of a Scaffoldmentioning

confidence: 99%

Recent Advances in Scaffold Design and Material for Vascularized Tissue‐Engineered Bone Regeneration

Yin

Zhang

Zhang³

et al. 2019

Adv Healthcare Materials

201

123

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Bone tissue is a highly vascularized tissue and concomitant development of the vascular system and mineralized matrix requires a synergistic interaction between osteogenesis and angioblasts. Several strategies have been applied to achieve vascularized tissue‐engineered bone, including the addition of cytokines as well as pre‐vascularization strategies and co‐culture systems. However, the scaffold is another extremely important component to consider, and development of vascularized bone scaffolds remains one of the greatest challenges for engineering clinically relevant bone substitutes. Here, this review highlights the biomaterial selection, preparation of pre‐vascularized scaffolds, composition modification of the scaffold, structural design, and the comprehensive use of the above synergistic modifications of scaffold materials for vascular scaffolds in bone tissue engineering. Moreover, a strategy is proposed for the design of future scaffold structures, in which promoting the regeneration of vascularized bone by regulating the microenvironment should be the main focus. This overview can help illuminate progress in this field and identify the most recently developed scaffolds that show the greatest potential for achieving clinically vascularized bone.

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A novel classification of bone graft materials

2022

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Over the past few decades, the field of biomaterials concerning bone tissue engineering has gained a significant amount of interest. This has led to new biomaterials to be used as bone substitute materials. Despite the rapid increase in the types and forms of bone substitutes, a comprehensive classification encompassing all types of bone graft materials that have so far been developed and evaluated is lacking. Therefore, this review aims to integrate and bring together the published data on bone substitutes within the last 5 years and produce a novel classification that would provide bone material researchers with a better understanding of what materials have so far been used and evaluated and the areas, where research is lacking and deserves more attention. The literature available in all major databases was obtained and filtered using an elimination criterion to extract all the articles related to studies that tested bone substitute materials in nonclinical and clinical trials over the last 5 years. The review article would provide bone material researchers with an insight into the materials that have been evaluated for bone tissue engineering applications and identify future perspectives for bone graft material research.

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Reconstruction of large mandibular defects using autologous tissues generated from in vivo bioreactors

Cited by 35 publications

References 29 publications

Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Recent Advances in Scaffold Design and Material for Vascularized Tissue‐Engineered Bone Regeneration

A novel classification of bone graft materials

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