Elastomeric Cell-Laden Nanocomposite Microfibers for Engineering Complex Tissues
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Biomaterials-based three dimensional scaffolds with tunable elasticity hold promise in replacing failed organs resulting from injuries, aging, and diseases by providing a suitable cellular microenvironment to facilitate regeneration of damaged tissues. However, controlled presentation of biological signals with tunable tissue mechanics and architecture remain a bottleneck that needs to be addressed to engineer functional artificial tissues. Nanocomposite hydrogels that promote cells adhesion and demonstrate tunable viscoelastic properties could mimic key properties and structures of native tissue. We have developed elastomeric fiber shaped cellular constructs from poly(ethylene glycol) diacrylate, silicate nanoparticles, and gelatin methacrylate via ionic and covalent crosslinking. By controlling the interactions between nanoparticles and polymers, nanocomposite hydrogels with tunable mechanical and degradation properties are fabricated. By encapsulating multiple cell types in these cellular constructs, we demonstrate materials-based control of cell spreading, survival, and proliferation. As a proof-of-concept, we assembled the hydrogel microfibers to obtain multicellular elastomeric tissue constructs. These elastic microfibers may serve as model systems to explore the effect of mechanical stress on cell–matrix interactions. Moreover, such elastomeric hydrogel fibers can be used to engineer scaffold structures, fabric sheets, bundles, or as building blocks for 3D tissue construction.
KeywordsNanocomposite hydrogels Nanoparticles Microfibers Cell–matrix interactions Tissue engineering Bioadhesive
We would like to acknowledge Lauren Cross for hydrogel preparation, and Manish K. Jaiswal for SEM imaging. Ravi G. Patel of Cornell University for establishing focal adhesion protocol. We also like to thank Prof. Roland Kaunas (Texas A&M University) for providing RFP-mosJ cells.
Conflict of interest
Charles W. Peak, James K. Carrow, Ashish Thakur, Ankur Singh, and Akhilesh K. Gaharwar declare that they have no conflicts of interest.
No animal or human studies were carried out by the authors for this article.
- 3.Cayrol, F., M. C. Diaz Flaque, T. Fernando, S. N. Yang, H. A. Sterle, M. Bolontrade, M. Amoros, B. Isse, R. N. Farias, H. Ahn, Y. F. Tian, F. Tabbo, A. Singh, G. Inghirami, L. Cerchietti, and G. A. Cremaschi. Integrin alphavbeta3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells. Blood 125(5):841–851, 2015.CrossRefGoogle Scholar
- 6.Coyer, S. R., A. Singh, D. W. Dumbauld, D. A. Calderwood, S. W. Craig, E. Delamarche, and A. J. García. Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension. J. Cell Sci. 125(21):5110–5123, 2012.CrossRefGoogle Scholar
- 10.Gaharwar, A. K., V. Kishore, C. Rivera, W. Bullock, C. J. Wu, O. Akkus, and G. Schmidt. Physically crosslinked nanocomposites from silicate-crosslinked peo: mechanical properties and osteogenic differentiation of human mesenchymal stem cells. Macromol. Biosci. 12(6):779–793, 2012.CrossRefGoogle Scholar
- 20.Karimi, A., and M. Navidbakhsh. Material properties in unconfined compression of gelatin hydrogel for skin tissue engineering applications. Biomed. Eng. Biomed. Tech. 59(6):479–486, 2014.Google Scholar
- 22.Lee, T. T., J. R. Garcia, J. I. Paez, A. Singh, E. A. Phelps, S. Weis, Z. Shafiq, A. Shekaran, A. Del Campo, and A. J. Garcia. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat. Mater. 14(3):352–360, 2014.CrossRefGoogle Scholar
- 38.Santos, M. I., K. Tuzlakoglu, S. Fuchs, M. E. Gomes, K. Peters, R. E. Unger, E. Piskin, R. L. Reis, and C. J. Kirkpatrick. Endothelial cell colonization and angiogenic potential of combined nano- and micro-fibrous scaffolds for bone tissue engineering. Biomaterials 29(32):4306–4313, 2008.CrossRefGoogle Scholar