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.
|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|
|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|
|Appel, Eric A; Tibbitt, Mark W; Webber, Matthew J et al. (2015) Self-assembled hydrogels utilizing polymer-nanoparticle interactions. Nat Commun 6:6295|
|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|
|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|
|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|
|Jhunjhunwala, Siddharth; Aresta-DaSilva, Stephanie; Tang, Katherine et al. (2015) Neutrophil Responses to Sterile Implant Materials. PLoS One 10:e0137550|
|Hook, Andrew L; Chang, Chien-Yi; Scurr, David J et al. (2014) Thermally switchable polymers achieve controlled Escherichia coli detachment. Adv Healthc Mater 3:1020-5|
|Dong, Yizhou; Eltoukhy, Ahmed A; Alabi, Christopher A et al. (2014) Lipid-like nanomaterials for simultaneous gene expression and silencing in vivo. Adv Healthc Mater 3:1392-7|
Showing the most recent 10 out of 64 publications