We propose to use our established and well documented history in the development of biomaterials as scaffolding for tissue replacement as a platform for stem cell approaches in craniofacial tissue regeneration. The governing hypotheses of this work include: i) that human stem cells of embryonic origin can be differentiated into craniofacial tissue producing cells such as osteoblasts and chondrocytes, ii) that highthroughput techniques can be used for the screening of large numbers of media and polymer candidates for potential use with tissue engineering scaffolds, and iii) that the appropriate combination of stem cells with 3-dimensional polymer scaffolds can be used for the production of complex craniofacial tissues. To test these hypotheses, we propose the following:
Aim 1 : Examine the in vitro differentiation of human embryonic stem cells into precursors of craniofacial tissues. Our previous work investigating the in vitro differentiation of human embryonic stem cells into various cell types and tissues will be continued to assess conditions necessary for differentiation into cell types necessary for craniofacial tissue formation.
Aim 2 : Investigate the interaction of human stem cells with polymer surfaces using high-throughput screening technology. Recently, we have developed techniques for the rapid screening of cell/polymer interactions using nanoliter-scale microarrays of various monomers and polymers. Success will be assessed through cell proliferation and the presence of tissue specific markers for craniofacial tissues.
Aim 3 : Assess in vitro tissue production by differentiated and undifferentiated human embryonic stem cell seeded polymeric scaffolds incorporating various genes and growth factors. Polymeric materials that support the differentiation of human stem cells into craniofacial tissues will be fabricated into 3-dimensional scaffolds incorporating various genes and growth factors and analyzed by histological staining of various markers.
Aim 4 : Optimal candidates from the previous aims will be seeded with differentiated and undifferentiated cells and implanted either subcutaneously or in a critical sized defect model in rats. The subcutaneous model in athymic rats will be used to assess tissue production by stem cell seeded scaffolds in an in vivo environment, including scaffolds with cells differentiated into multiple phenotypes. The cranial defect model in athymic rats is a clinically relevant model that is commonly used as a measure of bone regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016516-04
Application #
7385976
Study Section
Special Emphasis Panel (ZDE1-YL (03))
Program Officer
Lumelsky, Nadya L
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$369,782
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Dong, Yizhou; Dorkin, J Robert; Wang, Weiheng et al. (2016) Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo. Nano Lett 16:842-8
Yin, Hao; Bogorad, Roman L; Barnes, Carmen et al. (2016) RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver. J Hepatol 64:899-907
Luo, X; Wang, W; Dorkin, J R et al. (2016) Poly(glycoamidoamine) brush nanomaterials for systemic siRNA delivery in vivo. Biomater Sci 5:38-40
Patel, Asha K; Celiz, Adam D; Rajamohan, Divya et al. (2015) A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays. Biomaterials 61:257-65
Appel, Eric A; Tibbitt, Mark W; Webber, Matthew J et al. (2015) Self-assembled hydrogels utilizing polymer-nanoparticle interactions. Nat Commun 6:6295
White, Kevin; Lu, Yu; Annis, Sofia et al. (2015) Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension. EMBO Mol Med 7:695-713
Sydlik, Stefanie A; Jhunjhunwala, Siddharth; Webber, Matthew J et al. (2015) In vivo compatibility of graphene oxide with differing oxidation states. ACS Nano 9:3866-74
Appel, Eric A; Larson, Benjamin L; Luly, Kathryn M et al. (2015) Non-cell-adhesive substrates for printing of arrayed biomaterials. Adv Healthc Mater 4:501-5
Jhunjhunwala, Siddharth; Aresta-DaSilva, Stephanie; Tang, Katherine et al. (2015) Neutrophil Responses to Sterile Implant Materials. PLoS One 10:e0137550
Bogorad, Roman L; Yin, Hao; Zeigerer, Anja et al. (2014) Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice. Nat Commun 5:3869

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