Skip to main content
Log in

Elastomeric Cell-Laden Nanocomposite Microfibers for Engineering Complex Tissues

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Annabi, N., J. W. Nichol, X. Zhong, C. Ji, S. Koshy, A. Khademhosseini, and F. Dehghani. Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng. B 16(4):371–383, 2010.

    Article  Google Scholar 

  2. Carrow, J. K., and A. K. Gaharwar. Bioinspired polymeric nanocomposites for regenerative medicine. Macromol. Chem. Phys. 216(3):248, 2015.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  4. Chan, B. K., C. C. Wippich, C.-J. Wu, P. M. Sivasankar, and G. Schmidt. Robust and semi-interpenetrating hydrogels from poly(ethylene glycol) and collagen for elastomeric tissue scaffolds. Macromol. Biosci. 12(11):1490–1501, 2012.

    Article  Google Scholar 

  5. Chaudhuri, O., S. T. Koshy, C. B. da Cunha, J. W. Shin, C. S. Verbeke, K. H. Allison, and D. J. Mooney. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat. Mater. 13(10):970–978, 2014.

    Article  Google 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.

    Article  Google Scholar 

  7. Dumbauld, D. W., T. T. Lee, A. Singh, J. Scrimgeour, C. A. Gersbach, E. A. Zamir, J. Fu, C. S. Chen, J. E. Curtis, and S. W. Craig. How vinculin regulates force transmission. Proc. Natl. Acad. Sci. 110(24):9788–9793, 2013.

    Article  Google Scholar 

  8. Dvir, T., B. P. Timko, D. S. Kohane, and R. Langer. Nanotechnological strategies for engineering complex tissues. Nat. Nanotechnol. 6(1):13–22, 2011.

    Article  Google Scholar 

  9. Gaharwar, A. K., R. K. Avery, A. Assmann, A. Paul, G. H. McKinley, A. Khademhosseini, and B. D. Olsen. Shear-thinning nanocomposite hydrogels for the treatment of hemorrhage. ACS Nano 8(10):9833–9842, 2014.

    Article  Google 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.

    Article  Google Scholar 

  11. Gaharwar, A. K., S. M. Mihaila, A. Swami, A. Patel, S. Sant, R. L. Reis, A. P. Marques, M. E. Gomes, and A. Khademhosseini. Bioactive silicate nanoplatelets for osteogenic differentiation of human mesenchymal stem cells. Adv. Mater. 25(24):3329–3336, 2013.

    Article  Google Scholar 

  12. Gaharwar, A. K., N. A. Peppas, and A. Khademhosseini. Nanocomposite hydrogels for biomedical applications. Biotechnol. Bioeng. 111(3):441–453, 2014.

    Article  Google Scholar 

  13. Gaharwar, A. K., P. J. Schexnailder, A. Dundigalla, J. D. White, C. R. Matos-Pérez, J. L. Cloud, S. Seifert, J. J. Wilker, and G. Schmidt. Highly extensible bio-nanocomposite fibers. Macromol. Rapid Commun. 32(1):50–57, 2011.

    Article  Google Scholar 

  14. Gaharwar, A. K., P. J. Schexnailder, B. P. Kline, and G. Schmidt. Assessment of using Laponite® cross-linked poly(ethylene oxide) for controlled cell adhesion and mineralization. Acta Biomater. 7(2):568–577, 2011.

    Article  Google Scholar 

  15. Giano, M. C., Z. Ibrahim, S. H. Medina, K. A. Sarhane, J. M. Christensen, Y. Yamada, G. Brandacher, and J. P. Schneider. Injectable bioadhesive hydrogels with innate antibacterial properties. Nat. Commun. 5:4095, 2014.

    Article  Google Scholar 

  16. Hern, D. L., and J. A. Hubbell. Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing. J. Biomed. Mater. Res. 39(2):266–276, 1998.

    Article  Google Scholar 

  17. Hoffman, A. S. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 64:18–23, 2012.

    Article  Google Scholar 

  18. Hoffman, A. S. Stimuli-responsive polymers: Biomedical applications and challenges for clinical translation. Adv Drug Deliv Rev. 65(1):10–16, 2013.

    Article  Google Scholar 

  19. Hutson, C. B., J. W. Nichol, H. Aubin, H. Bae, S. Yamanlar, S. Al-Haque, S. T. Koshy, and A. Khademhosseini. Synthesis and characterization of tunable poly(ethylene glycol): gelatin methacrylate composite hydrogels. Tissue Eng. A 17(13–14):1713–1723, 2011.

    Article  Google 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 

  21. Kerativitayanan, P., J. K. Carrow, and A. K. Gaharwar. Nanomaterials for engineering stem cell responses. Adv. Healthc. Mater. 2015. doi:10.1002/adhm.201500272.

    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.

    Article  Google Scholar 

  23. Lee, K. Y., and D. J. Mooney. Hydrogels for tissue engineering. Chem. Rev. 101(7):1869–1880, 2001.

    Article  Google Scholar 

  24. Liu, Y., H. Meng, S. Konst, R. Sarmiento, R. Rajachar, and B. P. Lee. Injectable dopamine-modified poly(ethylene glycol) nanocomposite hydrogel with enhanced adhesive property and bioactivity. Acs Appl. Mater. Interfaces 6(19):16982–16992, 2014.

    Article  Google Scholar 

  25. Mellott, M. B., K. Searcy, and M. V. Pishko. Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization. Biomaterials 22(9):929–941, 2001.

    Article  Google Scholar 

  26. Mihaila, S. M., A. K. Gaharwar, R. L. Reis, A. Khademhosseini, A. P. Marques, and M. E. Gomes. The osteogenic differentiation of SSEA-4 sub-population of human adipose derived stem cells using silicate nanoplatelets. Biomaterials 35(33):9087–9099, 2014.

    Article  Google Scholar 

  27. Mooney, D. T., C. L. Mazzoni, C. Breuer, K. McNamara, D. Hern, J. P. Vacanti, and R. Langer. Stabilized polyglycolic acid fibre based tubes for tissue engineering. Biomaterials 17(2):115–124, 1996.

    Article  Google Scholar 

  28. Nguyen, K. T., and J. L. West. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23(22):4307–4314, 2002.

    Article  Google Scholar 

  29. Nichol, J. W., S. T. Koshy, H. Bae, C. M. Hwang, S. Yamanlar, and A. Khademhosseini. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31(21):5536–5544, 2010.

    Article  Google Scholar 

  30. Patel, R. G., A. Purwada, L. Cerchietti, G. Inghirami, A. Melnick, A. K. Gaharwar, and A. Singh. microscale bioadhesive hydrogel arrays for cell engineering applications. Cell. Mol. Bioeng. 7(3):394–408, 2014.

    Article  Google Scholar 

  31. Peak, C. W., S. Nagar, R. D. Watts, and G. Schmidt. Robust and degradable hydrogels from poly(ethylene glycol) and semi-interpenetrating collagen. Macromolecules 47(18):6408–6417, 2014.

    Article  Google Scholar 

  32. Peak, C. W., J. J. Wilker, and G. Schmidt. A review on tough and sticky hydrogels. Colloid Polym. Sci. 291(9):2031–2047, 2013.

    Article  Google Scholar 

  33. Peppas, N. A., P. Bures, W. Leobandung, and H. Ichikawa. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50(1):27–46, 2000.

    Article  Google Scholar 

  34. Peppas, N. A., J. Z. Hilt, A. Khademhosseini, and R. Langer. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18(11):1345–1360, 2006.

    Article  Google Scholar 

  35. Peppas, N. A., K. B. Keys, M. Torres-Lugo, and A. M. Lowman. Poly(ethylene glycol)-containing hydrogels in drug delivery. J. Control. Release 62(1–2):81–87, 1999.

    Article  Google Scholar 

  36. Purwada, A., M. K. Jaiswal, H. Ahn, T. Nojima, D. Kitamura, A. K. Gaharwar, L. Cerchietti, and A. Singh. Ex vivo engineered immune organoids for controlled germinal center reactions. Biomaterials 63:24–34, 2015.

    Article  Google Scholar 

  37. Qiu, Y., and K. Park. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev. 64:49–60, 2012.

    Article  Google 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.

    Article  Google Scholar 

  39. Shingleton, W. D., D. J. Hodges, P. Brick, and T. E. Cawston. Collagenase: a key enzyme in collagen turnover. Biochem. Cell Biol. 74(6):759–775, 1996.

    Article  Google Scholar 

  40. Singh, A., and N. A. Peppas. Hydrogels and scaffolds for immunomodulation. Adv. Mater. 26(38):6530–6541, 2014.

    Article  Google Scholar 

  41. Ullm, S., A. Kruger, C. Tondera, T. P. Gebauer, A. T. Neffe, A. Lendlein, F. Jung, and J. Pietzsch. Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties. Biomaterials 35(37):9755–9766, 2014.

    Article  Google Scholar 

  42. Xavier, J. R., T. Thakur, P. Desai, M. K. Jaiswal, N. Sears, E. Cosgriff-Hernandez, R. Kaunas, and A. K. Gaharwar. Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach. ACS Nano 9(3):3109–3118, 2015.

    Article  Google Scholar 

Download references

Acknowledgments

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.

Ethical Standards

No animal or human studies were carried out by the authors for this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Akhilesh K. Gaharwar.

Additional information

Associate Editor Christine Schmidt oversaw the review of this article.

This article is part of the 2015 Young Innovators Issue.

Akhilesh K. Gaharwar is an Assistant Professor in the Department of Biomedical Engineering at Texas A&M University, where he directs the Inspired Nanomaterials and Tissue Engineering Laboratory. His research interest includes nanomaterials, cell-nanomaterials interactions, stem cell biology, and tissue engineering. His current research effort centers on creating bioactive nanomaterials for modulating the behavior of stem cells and understanding underlying nanomaterials induced cell signaling for developing bioengineering strategies. Dr. Gaharwar received his Ph.D. in Biomedical Engineering at Purdue University and postdoctoral training at Massachusetts Institute of Technology and Harvard University. Over 14 major international awards have recognized Dr. Gaharwar’s interdisciplinary research. He receives awards from three major societies: biomedical (2011 BMES Graduate Award, 2013 CMBE - BMES Rising Star/Fellows), materials science (2011 MRS Silver Award), and biomaterials (2010 Society For Biomaterials – STAR). He was awarded the prestigious “2010 Dimitris N. Chorafas Foundation Award” for an outstanding Ph.D dissertation. Other notable awards include “2011 ACTA Student Award”, “2005 DAAD Fellowship” and “2004 MHRD Fellowship”. He has published peer-reviewed research articles in Advanced Materials, ACS Nano, Advanced Functional Materials, Biomaterials, Acta Biomaterialia, Biomacromolecules, Journal of Controlled Release, and Tissue Engineering Part A.

figure a

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peak, C.W., Carrow, J.K., Thakur, A. et al. Elastomeric Cell-Laden Nanocomposite Microfibers for Engineering Complex Tissues. Cel. Mol. Bioeng. 8, 404–415 (2015). https://doi.org/10.1007/s12195-015-0406-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-015-0406-7

Keywords

Navigation