Regeneration of normal shape, architecture and function of craniofacial tissues due to congenital abnormality, trauma or surgical treatment presents special problems to tissue engineering. Because of the great variations in properties of these tissues, currently available treatment options fall short of adequate care. The availability of customized living tissues engineered in vitro would revolutionize the way we currently treat craniofacial defects. In the 1st grant cycle, we established a tissue engineering approach to craniofacial reconstruction based on anatomically shaped cartilage/bone grafts formed using human stem cells, composite scaffolds and perfusion/loading bioreactors. From these studies, we published 74 peer-reviewed journal articles, 27 of which were coauthored by the two laboratories (Columbia University and Tufts University). For the 2nd grant cycle, we will maintain our focus on the temporomandibular joint (TMJ) and build upon the results of the 1st cycle to make advances in three important areas: (i) Develop composite scaffolds mimicking the internal architectures of craniofacial tissues, (ii) Integrate bioreactors with live imaging to study tissue development without interrupting cultivation, and (iii) Conduct a large animal study of craniofacial reconstruction. The research plan has been designed for impact in two areas: (i) Customized approach to craniofacial reconstruction, and (ii) Quantitative insights into the formation of craniofacial tissues, using an advanced bioreactor-imaging system and a clinically relevant animal model. Our overall hypothesis is that craniofacial grafts can be formed by biophysical regulation of adult human stem cells using a biomimetic scaffold-bioreactor system. We will engineer the TMJ condyle and the TMJ disc, two important and interacting jaw components, with complex architectures and mechanical loading, but with distinct structures.
Three specific aims will be pursued:
Aim 1 - Develop anatomically shaped scaffolds for engineering TMJ condyle and disc, with their characteristic structural and biomechanical anisotropies, Aim 2 - Engineer customized craniofacial tissues using an advanced bioreactor-imaging platform, and Aim 3 - Evaluate the tissue engineering approach to craniofacial reconstruction in a large animal model (Yucatan pig).
BROADER IMPACT Damage or malformation of bone in head and face due to trauma, surgical treatment or birth defects not only leave the patient with the loss of tissue, but also render them psychologically scarred. Radically new approaches are necessary for advancing our ability to precisely reconstruct the normal anatomy and function of the head and face. The proposed studies are designed to enable in-depth understanding of the factors important for full regeneration of the bones of head and face, and to use this knowledge to develop a tissue engineering approach customized to the patient and the defect being treated.
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|Wobma, Holly; Vunjak-Novakovic, Gordana (2016) Tissue Engineering and Regenerative Medicine 2015: A Year in Review. Tissue Eng Part B Rev 22:101-13|
|Bernhard, Jonathan C; Vunjak-Novakovic, Gordana (2016) Should we use cells, biomaterials, or tissue engineering for cartilage regeneration? Stem Cell Res Ther 7:56|
|Cigan, Alexander D; Roach, Brendan L; Nims, Robert J et al. (2016) High seeding density of human chondrocytes in agarose produces tissue-engineered cartilage approaching native mechanical and biochemical properties. J Biomech 49:1909-17|
|Bhumiratana, Sarindr; Bernhard, Jonathan C; Alfi, David M et al. (2016) Tissue-engineered autologous grafts for facial bone reconstruction. Sci Transl Med 8:343ra83|
|Cigan, Alexander D; Durney, Krista M; Nims, Robert J et al. (2016) Nutrient Channels Aid the Growth of Articular Surface-Sized Engineered Cartilage Constructs. Tissue Eng Part A 22:1063-74|
|Cigan, Alexander D; Nims, Robert J; Vunjak-Novakovic, Gordana et al. (2016) Optimizing nutrient channel spacing and revisiting TGF-beta in large engineered cartilage constructs. J Biomech 49:2089-94|
|Spiller, Kara L; Freytes, Donald O; Vunjak-Novakovic, Gordana (2015) Macrophages modulate engineered human tissues for enhanced vascularization and healing. Ann Biomed Eng 43:616-27|
|Yodmuang, Supansa; McNamara, Stephanie L; Nover, Adam B et al. (2015) Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair. Acta Biomater 11:27-36|
|Spiller, Kara L; Nassiri, Sina; Witherel, Claire E et al. (2015) Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37:194-207|
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