Practical Use of Hydrogels in Stereolithography for Tissue Engineering Applications

  • Karina Arcaute
  • Brenda K. Mann
  • Ryan B. Wicker


In recent years, additive manufacturing (AM) or rapid prototyping (RP) technologies, initially developed to create prototypes prior to production for the automotive, aerospace, and other industries, have found applications in tissue engineering (TE) and their use is growing rapidly. RP technologies are increasingly demonstrating the potential for fabricating biocompatible 3D structures with precise control of the micro- and macro-scale characteristics. Several comprehensive reviews on the use of RP technologies, also known as solid freeform fabrication, Additive Manufacturing, direct digital manufacturing, and other names, have been published recently [1–4].


Geometric Accuracy Energy Dosage Rapid Prototype Technology Laser Speed Hatch Spacing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The research presented here was performed at the University of Texas at El Paso (UTEP) within the W.M. Keck Center for 3D Innovation (Keck Center). Primary support for this research was provided by the National Science Foundation through Grant No. CBET-0730750. The authors are grateful to the many faculty, staff, and students within the Keck Center who assisted in various ways with this research. Equipment and facilities in the UTEP Analytical Cytology Core Facility of the Biological Sciences Department used here are maintained through NCRR Grant Number 5G12 RR008124. Any opinions, findings, and conclusions or recommendations expressed in this work are those of the authors and do not necessarily reflect the views of the National Science Foundation or any other individual or funding agency.


  1. 1.
    Leong, K.F., C.M. Cheah, and C.K. Chua. Solid freeform fabrication of three-dimensional scaffolds for engineering replacements tissues and organs. Biomaterials 24: 2363-2378, 2003.CrossRefGoogle Scholar
  2. 2.
    Liu, V. and S.N. Bhatia. Three-dimensional tissue fabrication. Advanced Drug Delivery Reviews 56: 1635–1647, 2004.CrossRefGoogle Scholar
  3. 3.
    Hutmacher, D.W. and M.A. Woodruff. Design, Fabrication, and Characterization of Scaffolds via Solid Free-Form Fabrication Techniques. In: Biomaterials Fabrication and Processing Handbook, edited by P.K. Chu and X. Liu. Boca Raton, FL: CRC Press, Taylor & Francis Group, 2008, pp. 45–67.Google Scholar
  4. 4.
    Vozzi, G. and A. Ahluwalia. Rapid Prototyping Methods for Tissue Engineering Applications. In: Biomaterials Fabrication and Processing Handbook, edited by P.K. Chu and X. Liu. Boca Raton, FL: CRC Press, Taylor & Francis Group, 2008, pp. 95–114CrossRefGoogle Scholar
  5. 5.
    Ang, T.H., F.S.A. Sultana, D.W. Hutmacher, Y.S. Wong, J.Y.H. Fuh, X.M. Mo, H.T. Loh, and S.H. Teoh. Fabrication of 3D chitosan-hydroxyapatite scaffolds using a robotic dispensing system. Materials Science and Engineering C 20: 35–42, 2002.CrossRefGoogle Scholar
  6. 6.
    Landers, R., U. Hubner, R. Schmelzeisen and R. Mulhaupt. Rapid prototyping of scaffolds derived from thermoreversible hydrogels and tailored for applications in tissue engineering. Biomaterials 23: 4437–4447, 2002CrossRefGoogle Scholar
  7. 7.
    Vozzi, G., C. Flaim, A. Ahluwalia, and S. Bhatia. Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition. Biomaterials 24: 2533–2540, 2003.CrossRefGoogle Scholar
  8. 8.
    Vozzi, G., V. Chiono, G. Ciardelli, P. Giusti, A. Previti, C. Cristallini, N. Barbani, G. Tantussi, and A. Ahluwalia. Microfabrication of biodegradable polymeric structures for guided tissue engineering. Materials Research Society Symposium Proceedings, EXS-1: F5.22.1–3, 2004.Google Scholar
  9. 9.
    Wiria, F.E., K.F. Leong, and Y. Liu. Poly-ε-caprolactone/hydroxiapatite for tissue engineering scaffold fabrication via selective laser sintering. Acta Biomaterialia 3: 1–12, 2007.CrossRefGoogle Scholar
  10. 10.
    Tan, K.H., C.K. Chua, K.F. Leong, C.M. Cheah, P. Cheang, M.S. Abu Bakar, and S.W. Cha. Scaffold development using selective laser sintering of polyetherketone-hydroxyapatite biocomposite blends. Biomaterials 24: 3115–3123, 2003.CrossRefGoogle Scholar
  11. 11.
    Hutmacher, D.W., T. Schantz, I. Zein, K.W. Ng, S.H. Teoh, and K.C. Tan. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. Journal of Biomedical Materials Research 55(2): 203–216, 2001.CrossRefGoogle Scholar
  12. 12.
    Zein, I., D.W. Hutmacher, K.C. Tan, and S.H. Teoh. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials 23: 1169–1185, 2002.CrossRefGoogle Scholar
  13. 13.
    Chim, H., D.W. Hutmacher, A.M. Chou, A.L. Oliveira, R.L. Reis, T.C. Lim, and J.T. Schantz. A comparative analysis of scaffold material modifications for load-bearing applications in tissue engineering. International Journal of Oral and Maxillofacial Surgery 35: 928–934, 2006.CrossRefGoogle Scholar
  14. 14.
    Liu, V.A. and S.N. Bhatia. Three-dimensional photopatterning of hydrogels containing living cells. Biomedical Microdevices 4: 257–266, 2002.CrossRefGoogle Scholar
  15. 15.
    Hahn, M.S., Miller, J.S., and J.L. West. Laser scanning lithography for surface micropatterning on hydrogels. Advanced Materials 17: 2939–2942, 2005.CrossRefGoogle Scholar
  16. 16.
    Hahn, M.S. L.J. Taite, J.J. Moon, M.C. Rowland, K.A. Ruffino, and J.L. West. Photolithographic patterning of polyethylene glycol hydrogels. Biomaterials 27: 2519–2534, 2006.CrossRefGoogle Scholar
  17. 17.
    Hahn, M.S., Miller J.S., and J.L. West. Three-dimensional biochemical and biomechanical patterning of hydrogels for guiding cell behavior. Advanced Materials 18: 2679–2684, 2006.CrossRefGoogle Scholar
  18. 18.
    Luo, N., A.T. Metters, B. Hutchison, C.N. Bowman, and K.S. Anseth. A methacrylated photoiniferter as a chemical basis for microlithography: micropatterning based on photografting polymerization. Macromolecules 36: 6739–6745, 2003.CrossRefGoogle Scholar
  19. 19.
    Starly, B., R. Chang, and W. Sun. UV-Photolithography fabrication of poly-ethylene glycol hydrogels encapsulated with hepatocytes. Proceedings of the 17th Annual Solid Freeform Fabrication Symposium, University of Texas at Austin, August 1–3, 2006, pp 102–110.Google Scholar
  20. 20.
    Han, L.H., G. Mapili, S. Chen, and K. Roy. Freeform fabrication of biological scaffolds by projection photopolymerization. Proceedings of the 18th Annual Solid Freeform Fabrication Symposium, University of Texas at Austin, August 1–3, 2007, pp 450–457.Google Scholar
  21. 21.
    Han, L.H., G. Mapili, S. Chen, and K. Roy. Projection Microfabrication of three-dimensional scaffolds for tissue engineering. Transactions of ASME: Journal of Manufacturing Science and Engineering 130: 021005-1–021005-4, 2008.Google Scholar
  22. 22.
    Choi, J.W., R.B. Wicker, S.H. Cho, C.S. Ha, S.H. Lee. Cure depth control for complex 3D microstructure fabrication in dynamic mask projection microstereolithography. Rapid Prototyping Journal 15(1): 59–70, 2009.CrossRefGoogle Scholar
  23. 23.
    Choi, J.W., R.B. Wicker, S.H. Lee, K.H.Choi, C.S. Ha, and I. Chung. Fabrication of 3D biocompatible/biodegradable micro-scaffolds using dynamic mask projection microstereolithography. Journal of Materials Processing Technology, 209(15–16): 5494–5503, 2009.Google Scholar
  24. 24.
    Comeau, B.M., Umar, Y., Gonsalves, K.E., and Henderson, C.L. New materials and methods for hierarchically structured tissue scaffolds. Materials Research Society Symposium Proceedings, 845(A): AA4.4.1–6, 2005.Google Scholar
  25. 25.
    Bens, A.T., C. Tille, B. Leukers, G. Bermes, E. Emons, R. Sobe, A. Pansky, B. Roitzheim, M. Schulze, E. Tobiasch, and H. Seitz. Mechanical properties and bioanalytical characterization for a novel non-toxic flexible photopolymer formulation class. Proceedings of the 16th Annual Solid Freeform Fabrication Symposium, University of Texas at Austin, August 1–3, 2005, pp 162–173.Google Scholar
  26. 26.
    Cooke, M.N., J.P. Fisher, D. Dean, Rimnac, C. and A.G. Mikos. Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone in growth. Materials Research Part B: Applied Biomaterials 64B: 65–69, 2002.CrossRefGoogle Scholar
  27. 27.
    Lee, K.W., S. Wang, B.C. Fox, E.L. Ritman, M.J. Yaszemski, and L. Lu. Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. Biomacromolecules 8: 1077–1084, 2007.CrossRefGoogle Scholar
  28. 28.
    Popov, V.K., A.V. Evseev, A.L. Ivanov, V.V. Roginski, A.I. Volozhin, and S.M. Howdle. Laser stereolithography and super critical fluid processing for custom-designed implant fabrication. Journal of Materials Science: Materials in Medicine 15: 123–128, 2004.CrossRefGoogle Scholar
  29. 29.
    Barry, J.J.A., A.V. Evseev, M.A. Markov, C.E. Upton, C.A. Scotchford, V.K. Popov, and S.M. Howdle. In vitro study of hydroxyapatite-based photocurable polymer composites prepared by laser stereolithography and supercritical fluid extraction. Acta Biomaterialia 4(6): 1603–1610, 2008.Google Scholar
  30. 30.
    Dhariwala, B., Hunt, E., and Boland, T. Rapid prototyping of tissue engineering constructs, using photopolymerizable hydrogels and stereolithography. Tissue Engineering 9(10): 1316–1322, 2004.Google Scholar
  31. 31.
    Arcaute, K., L. Ochoa, F. Medina, C. Elkins, B. Mann, and Wicker, R. Three-dimensional PEG hydrogel construct fabrication using stereolithography. Materials Research Society Symposium Proceedings, 874:L5.5.1–L5.5.7, 2005.Google Scholar
  32. 32.
    Arcaute, K., L. Ochoa, B. Mann, and R. Wicker. Hydrogels in stereolithography. Proceedings of the 16th Annual Solid Freeform Fabrication Symposium, University of Texas at Austin, August 1–3, 2005.Google Scholar
  33. 33.
    Arcaute, K., L. Ochoa, B.K. Mann, and Wicker, R.B. Stereolithography of PEG hydrogel multi-lumen nerve regeneration conduits. ASME IMECE2005-81436 American Society of Mechanical Engineers International Mechanical Engineering Congress and Exposition, November 5–11, Orlando, Florida, 2005.Google Scholar
  34. 34.
    Wohlers, T., “Wohlers Report 2004: Rapid Prototyping, Tooling and Manufacturing, State of the Industry,” Wohlers Associates, Annual Worldwide Progress Report, 2004.Google Scholar
  35. 35.
    Sandoval, J.H., L. Ochoa, A. Hernandez, K.F. Soto, L.E. Murr, R.B. Wicker. Nanotailoring stereolithography resins for unique applications using carbon nanotubes. Proceedings of the 16th Annual Solid Freeform Fabrication Symposium, University of Texas at Austin, August 1–3, 2005.Google Scholar
  36. 36.
    Inamdar, A., M. Magana, F. Medina, Y. Grajeda, and R. Wicker. Development of an automated multiple material stereolithography machine. Proceedings of the 17th Annual Solid Freeform Fabrication Symposium, University of Texas at Austin, August 14–16, 2006.Google Scholar
  37. 37.
    Jacobs, P.F., Fundamental processes. In: Rapid Prototyping and Manufacturing: Fundamentals of Stereolithography, edited by P.F. Jacobs and D.T. Reid. Dearborn, Michigan: Society of Manufacturing Engineers, 1992, pp. 79–110.Google Scholar
  38. 38.
    Lee, I.H. and D.W. Cho. Micro-stereolithography photopolymer solidification patterns for various laser beam exposure conditions. International Journal of Advanced Manufacturing Technology 22: 410–416, 2003.CrossRefGoogle Scholar
  39. 39.
    Lee, J.H., R.K. Prud’homme, and I.A. Aksay. Cure depth in photopolymerization: experiments and theory. Journal of Material Research 16(2): 3536–3544, 2001.CrossRefGoogle Scholar
  40. 40.
    Jacobs, P.F. “Diagnostic testing.” In: Rapid Prototyping and Manufacturing: Fundamentals of Stereolithography, edited by P.F. Jacobs and D.T. Reid. Dearborn, Michigan: Society of Manufacturing Engineers, 1992, pp. 249–285.Google Scholar
  41. 41.
    D Systems. SLA-190/250 WindowpaneTM Building Procedure. In: 3D Systems AccumaxTM Toolkite User Guide. Valencia, California: 3D Systems, 1993.Google Scholar
  42. 42.
    DSM Somos®. Method 2: Determination of depth of penetration of photopolymer by a laser beam scan. DSM Somos® Revision 1, pp 1–4.Google Scholar
  43. 43.
    Bryant, S.J. and K.S. Anseth. The effect of scaffold thickness on tissue engineered cartilage in photocrosslinked poly(ethylene oxide) hydrogels. Biomaterials 22: 619–626, 2001.CrossRefGoogle Scholar
  44. 44.
    Bryant, S.J., K.S. Anseth, D.A. Lee, and D.L. Bader. Crosslinking density influences the morphology of chondrocytes photoencapsulated in PEG hydrogels during the application of compressive strain. Journal of Orthopaedic Research 22: 1143–1149, 2004.CrossRefGoogle Scholar
  45. 45.
    Burdick, J.A. and K.S. Anseth. Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 23: 4315–4323, 2002.CrossRefGoogle Scholar
  46. 46.
    Williams, C.G., T.K. Kim, A. Taboas, A. Malik, P. Manson, and J. Elisseeff. In vitro chondrogenesis of bone marrow derived mesenchymal stem cells in a photopolymerizing hydrogel. Tissue Engineering 9(4):679–688, 2003.CrossRefGoogle Scholar
  47. 47.
    Gunn, J.W., S.D. Turner, and B.K. Mann. Adhesive and mechanical properties of hydrogels influence neurite extension. Journal of Biomedical Materials Research, 72A (1):91–97, 2005.CrossRefGoogle Scholar
  48. 48.
    Mann, B.K., A.S. Gobin, A.T. Tsai, R.H. Schmedlen, and J.L. West. Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. Biomaterials 22: 3045–3051, 2001.CrossRefGoogle Scholar
  49. 49.
    Mann, B.K., R.H. Schmedlen, and J.L. West. Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells in peptide-modified scaffolds. Biomaterials, 22:439–44, 2001.CrossRefGoogle Scholar
  50. 50.
    Mann, B.K. and J.L. West. Cell adhesion peptides alter smooth muscle cell adhesion, proliferation, migration, and matrix protein synthesis on modified surfaces and in polymer scaffolds. Journal of Biomedical Materials Research, 60:86–93, 2002.CrossRefGoogle Scholar
  51. 51.
    Sawhney, A.S., C.P. Pathak, and J.A. Hubbell. Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(alpha-hydroxy acid) diacrylate macromers. Macromolecules 26:581–587, 1993.CrossRefGoogle Scholar
  52. 52.
    Zalispky, S. and J.M. Harris. “Introduction to chemistry and biological applications of poly(ethylene glycol),” Chapter 1. In: Poly(ethylene glycol) Chemistry and Biological Applications, edited by S. Zalispky and J.M. Harris. Washington, DC: American Chemical Society Series 680, 1997, pp. 1–13.Google Scholar
  53. 53.
    Nguyen, K.T. and J.L. West. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23: 4307-4314, 2002.CrossRefGoogle Scholar
  54. 54.
    Arcaute, K., B.K. Mann, and R.B. Wicker. Stereolithography of three-dimensional bioactive poly(ethylene glycol) constructs with encapsulated cells. Annals of Biomedical Engineering 34(9): 1429–1441, 2006.CrossRefGoogle Scholar
  55. 55.
    Fisher, J.P., J.W. Vehof, D. Dean, J.P. Van der Waerden, T.A. Holland, A.G. Mikos, and J.A. Jansen. Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model. Journal of Biomedical Materials Research 59(3): 547–556, 2002.CrossRefGoogle Scholar
  56. 56.
    Leach, J.B., K.A. Bivens, C.W. Patrick, and C.E. Schmidt. Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. Biotechnology and Bioengineering 82(5): 578–589, 2003.CrossRefGoogle Scholar
  57. 57.
    Burdick, J.A., C. Chung, X. Jia, M.A. Randolph and R. Langer. Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. Biomacromolecules 6: 386–391, 2005.CrossRefGoogle Scholar
  58. 58.
    Masters, K.S., D.N. Shah, L.A. Leinwand, and K.S. Anseth. Crosslinked hyaluronan scaffolds as biologically active carriers for valvular interstitial cells. Biomaterials 26: 2517–2525, 2005.CrossRefGoogle Scholar
  59. 59.
    Bryant, S.J., C.R. Nuttelman, and K.S. Anseth. Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro. Journal of Biomaterials Science, Polymer Edition, 11(5): 439–457, 2000.CrossRefGoogle Scholar
  60. 60.
    Williams, C.G., A.N. Malik, T.K. Kim, P.N. Manson, and J.H Elisseeff. Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. Biomaterials, 26: 1211–1218, 2005.CrossRefGoogle Scholar
  61. 61.
    Ciba Specialty Chemicals, Coatings Effects Segment. Ciba® Irgacure® 2959 Technical Data Sheet. Edition 2 4 98. Ciba Specialty Chemicals.Google Scholar
  62. 62.
    McCurdy, K.G. and K.J. Laidler. Rates of polymerization of acrylates and methacrylates in emulsion systems. Canadian Journal of Chemistry 42: 825–829, 1964.CrossRefGoogle Scholar
  63. 63.
    Klumperman, B. Pecularities in Atom Transfer Radical Copolimerization. Available online at Accessed on 05/2008.
  64. 64.
    Jacobs, P.F. “Introduction to part building.” In: Rapid Prototyping and Manufacturing: Fundamentals of Stereolithography, edited by P.F. Jacobs and D.T. Reid. Dearborn, Michigan: Society of Manufacturing Engineers, 1992, pp. 171–194.Google Scholar
  65. 65.
    Gayet, J.C., and G. Fortier. “New bioatificial hydrogels: characterization and physical properties.” In: Hydrogels and Biodegradable Polymers for Bioapplications, edited by R.M. Ottenbrite, S.J. Huang, and K. Park. Washington, D.C. American Chemical Society, 1996, pp. 17–24.Google Scholar
  66. 66.
    Jiankang, H, L. Dichen, L. Yaxiong, Y. Bo, L. Bingheng, and L. Qin. Fabrication and characterization of chitosan/gelatin porous scaffolds with predefined internal microstructures. Polymer, 48: 4578–4588, 2007.CrossRefGoogle Scholar
  67. 67.
    Arcaute, K., N. Zuverza, B.K. Mann, and R.B. Wicker. Multi-material stereolithography: spatially-controlled bioactive poly(ethylene glycol) scaffolds for tissue engineering. Proceedings of the 2007 Solid Freeform Fabrication Symposium, University of Texas at Austin, August 6-8, 2007.Google Scholar
  68. 68.
    Arcaute, K. Stereolithography of Poly(Ethylene Glycol) Hydrogels with Application in Tissue Engineering as Peripheral Nerve Regeneration Scaffolds. Ph.D. Dissertation. The University of Texas at El Paso. December, 2008.Google Scholar
  69. 69.
    Arcaute, K, B.K. Mann, and R.B. Wicker. Stereolithography of spatially-controlled multi-material bioactive poly(ethylene glycol) scaffolds. Acta Biomaterialia, 6: 1047–1054, 2010.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Karina Arcaute
  • Brenda K. Mann
  • Ryan B. Wicker
    • 1
  1. 1.W.M. Keck Center for 3D InnovationUniversity of Texas at El PasoEl PasoUSA

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