Autologously Generated Tissue-Engineered Bone Flaps for Reconstruction of Large Mandibular Defects in an Ovine Model

Tatara, Alexander M.; Kretlow, James D.; Spicer, Patrick P.; Lu, Shuaiyao; Lam, Johnny; Liu, Wei; Cao, Yilin; Liu, Guangpeng; Jackson, John D.; Yoo, James J.; Atala, Anthony; Beucken, Jeroen J.J.P. van den; Jansen, John A.; Kasper, F. Kurtis; Ho, Tang; Demian, Nagi; Miller, Michael J.; Wong, Mark E.; Mikos, Antonios G.

doi:10.1089/ten.tea.2014.0426

Cited by 32 publications

(46 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 54%

“…In total, 83.3% of the implanted bioreactors generated mineralized tissue suitable for transfer, an improvement compared with previous recent ovine bioreactor studies [50.0% (6) and 76.9% (5)]. By radiographic analysis, both biomaterials (synthetic beta-tricalcium phosphate/hydroxyapatite composite and morcellized AG) demonstrated significant changes in Tb.N.…”

Section: Discussionmentioning

confidence: 80%

“…The current state-of-the-art treatment for large mandibular defects, the fibula flap, is limited by the size and shape of the donor tissue. Therefore, we have developed a strategy in which engineered autologous flaps with customizable dimensions can be generated using the periosteum of the rib (5,6). In this study, we leveraged advances in biomaterials (3D printing and porous space maintenance technology) to (i) three-dimensionally print bioreactors with geometry and volume conforming to a mandibular defect and (ii) maintain the defect space and promote healthy soft tissue envelope formation during the period of time in which tissues can be generated from in vivo bioreactors for definitive reconstruction.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 4 more Smart Citations

Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Tatara

Koons

Watson

et al. 2019

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 54%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Tatara

Koons

Watson

et al. 2019

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

Self Cite

View full text Add to dashboard Cite

show abstract

Advanced Biotechnologies Toward Engineering a Cell Home for Stem Cell Accommodation

Tian

et al. 2017

Adv Materials Technologies

View full text Add to dashboard Cite

Biomaterials that exhibit bioinspired behavior enable a range of novel biomedical applications. Cell‐friendly biomaterials incorporating crucial physicochemical cues can instruct and dictate cell behavior both in vitro and in vivo. Despite substantial advances, engineering a complex cell regulatory system that incorporates mechanical and chemical signals targeting specific intracellular events has remained far from a reality. Recently, biological studies have begun to decipher the dynamic interplay between stem cells and their microenvironments. Moreover, the myriad recently developed advanced material biotechnologies, such as 3D bioprinting, protein engineering, release technology, high‐throughput screening, and microfluidics, have enabled the engineering of sophisticated biomaterial systems that increasingly closely mimic the spatial and temporal characteristics of the native cell milieu. Thus, biomaterials engineered in the laboratory not only provide a fertile environment for fostering stem cells but also exhibit properties that elicit favorable crosstalk between the structural components, the cells and the host tissue in a precise physiological manner, enabling balanced matrix generation and degradation for successful tissue regeneration to be achieved. This progress report discusses these advanced biotechnologies for the design, fabrication, and functionalization of biomaterials, highlighting their merits over traditional methodologies for mimicking the structural and mechanical properties of their natural in vivo counterparts.

show abstract

A novel classification of bone graft materials

2022

View full text Add to dashboard Cite

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.

show abstract

Autologously Generated Tissue-Engineered Bone Flaps for Reconstruction of Large Mandibular Defects in an Ovine Model

Cited by 32 publications

References 33 publications

Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Advanced Biotechnologies Toward Engineering a Cell Home for Stem Cell Accommodation

A novel classification of bone graft materials

Contact Info

Product

Resources

About