Interpenetrating polymer network hydrogel scaffolds for artificial cornea periphery

  • Rachel Parke-Houben
  • Courtney H. Fox
  • Luo Luo Zheng
  • Dale J. Waters
  • Jennifer R. Cochran
  • Christopher N. Ta
  • Curtis W. Frank
Clinical Applications of Biomaterials
Part of the following topical collections:
  1. Clinical Applications of Biomaterials


Three-dimensional scaffolds based on inverted colloidal crystals (ICCs) were fabricated from sequentially polymerized interpenetrating polymer network (IPN) hydrogels of poly(ethyleneglycol) and poly(acrylic acid). This high-strength, high-water-content IPN hydrogel may be suitable for use in an artificial cornea application. Development of a highly porous, biointegrable region at the periphery of the artificial cornea device is critical to long-term retention of the implant. The ICC fabrication technique produced scaffolds with well-controlled, tunable pore and channel dimensions. When surface functionalized with extracellular matrix proteins, corneal fibroblasts were successfully cultured on IPN hydrogel scaffolds, demonstrating the feasibility of these gels as materials for the artificial cornea porous periphery. Porous hydrogels with and without cells were visualized non-invasively in the hydrated state using variable-pressure scanning electron microscopy.


Interpenetrate Polymer Network Corneal Epithelial Cell Polystyrene Microsphere Hydrogel Scaffold Hydrogel Surface 
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 authors acknowledge the National Institutes of Health (NIH) Grant R01 EY016987-03 and the Singapore Eye Research Institute for funding.


  1. 1.
    Zeng Y, Yang J, Huang K, Lee Z, Lee X. A comparison of biomechanical properties between human and porcine cornea. J Biomech. 2001;34:533–7.CrossRefGoogle Scholar
  2. 2.
    National Advisory Eye Council. National plan for eye and vision research. National Institutes of Health; 2004.Google Scholar
  3. 3.
    Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull. World Health Org. 2001;79:214–21.Google Scholar
  4. 4.
    Myung D, Koh W, Bakri A, Zhang F, Marshall A, Ko J, et al. Design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct. Biomed. Microdev. 2007;9:911–22.CrossRefGoogle Scholar
  5. 5.
    Myung D, Farooqui N, Waters D, Schaber S, Koh W, Carrasco M, et al. Glucose-permeable interpenetrating polymer network hydrogels for corneal implant applications: a pilot study. Curr Eye Res. 2008;33:29–43.CrossRefGoogle Scholar
  6. 6.
    Marshall AJ, Ratner BD. Quantitative characterization of sphere-templated porous biomaterials. AIChE J. 2005;51:1221–32.CrossRefGoogle Scholar
  7. 7.
    Galperin A, Long TJ, Ratner BD. Degradable, thermo-sensitive poly(N-isopropyl acrylamide)-based scaffolds with controlled porosity for tissue engineering applications. Biomacromolecules. 2010;11:2583–92.CrossRefGoogle Scholar
  8. 8.
    Lee J, Shanbhag S, Kotov NA. Inverted colloidal crystals as three-dimensional microenvironments for cellular co-cultures. J Mater Chem. 2006;16:3558–64.CrossRefGoogle Scholar
  9. 9.
    Myung D, Farooqui N, Zheng LL, Koh W, Gupta S, Bakri A, et al. Bioactive interpenetrating polymer network hydrogels that support corneal epithelial wound healing. J Biomed Mater Res. 2009;90A:70–81.CrossRefGoogle Scholar
  10. 10.
    Jue B, Maurice DM. The mechanical properties of the rabbit and human cornea. J Biomech. 1986;19:847–53.CrossRefGoogle Scholar
  11. 11.
    Elsheikh A, Wang D, Pye D. Determination of the modulus of elasticity of the human cornea. J Refract Surg. 2007;23:808–18.Google Scholar
  12. 12.
    Xiao W, He J, Nichol JW, Wang L, Hutson CB, Wang B, et al. Synthesis and characterization of photocross linkable gelatin and silk fibroin interpenetrating polymer network hydrogels. Acta Biomater. 2011;7:2384–93.CrossRefGoogle Scholar
  13. 13.
    Nyquist GW. Rheology of the cornea: experimental techniques and results. Exp Eye Res. 1968;7:183–8.CrossRefGoogle Scholar
  14. 14.
    Chung C, Kang JY, Yoon I, Hwang H, Balakrishnan P, Cho H, et al. Interpenetrating polymer network (IPN) scaffolds of sodium hyaluronate and sodium alginate for chondrocyte culture. Coll. Surf. B: Biointerfaces. 2011;88:711–6.CrossRefGoogle Scholar
  15. 15.
    Kotov NA, Liu Y, Wang S, Cumming C, Eghtedari M, Vargas G, et al. Inverted colloidal crystals as three-dimensional cell scaffolds. Langmuir. 2004;20:7887–92.CrossRefGoogle Scholar
  16. 16.
    Zhang Y, Wang S, Eghtedari M, Motamedi M, Kotov NA. Inverted-colloidal-crystal hydrogel matrices as three-dimensional cell scaffolds. Adv Funct Mater. 2005;15:725–31.CrossRefGoogle Scholar
  17. 17.
    Sehgal D, Vijay IK. A method for the high efficiency of water-soluble carbodiimide-mediated amidation. Anal Biochem. 1994;218:87–91.CrossRefGoogle Scholar
  18. 18.
    Joubert LM. Visualization of hydrogels with variable-pressure SEM. Microsc Microanal. 2009;15:1308–9.CrossRefGoogle Scholar
  19. 19.
    Myung D, Koh W, Ko J, Hu Y, Carrasco M, Noolandi J, et al. Biomimetic strain hardening in interpenetrating polymer network hydrogels. Polymer. 2007;48:5376–87.CrossRefGoogle Scholar
  20. 20.
    Conway JH, Sloane NJA. Sphere packings, lattices, and groups. 3rd ed. New York: Springer; 1999.CrossRefGoogle Scholar
  21. 21.
    Wang X, Haasch RT, Bohn PW. Anisotropic hydrogel thickness gradient films derivatized to yield three-dimensional composite materials. Langmuir. 2005;21:8452–9.CrossRefGoogle Scholar
  22. 22.
    Engberg K, Frank CW. Protein diffusion in photopolymerized poly(ethylene glycol) hydrogel networks. Biomed Mater. 2011;6:055006.CrossRefGoogle Scholar
  23. 23.
    Salem AK, Stevens R, Pearson RG, Davies MC, Tendler SJB, Roberts CJ, et al. Interactions of 3T3 fibroblasts and endothelial cells with defined pore features. J Biomed Mater Res. 2002;61:212–7.CrossRefGoogle Scholar
  24. 24.
    Sun G, Zhang X, Chu C. Effect of the molecular weight of polyethylene glycol (PEG) on the properties of chitosan-PEG-poly(N-isopropylacrylamide) hydrogels. J Mater Sci Mater Med. 2008;19:2865–72.CrossRefGoogle Scholar
  25. 25.
    Zeltinger J, Sherwood JK, Graham DA, Mueller R, Griffith LG. Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. Tiss. Eng. 2001;7:557–72.CrossRefGoogle Scholar
  26. 26.
    Kwon IK, Park KD, Choi SW, Lee S, Lee EB, Na JS, et al. Fibroblast culture on surface-modified poly(glycolide-co-epsilon-caprolactone) scaffold for soft tissue regeneration. J Biomater Sci Polym Ed. 2001;12:1147–60.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Rachel Parke-Houben
    • 1
  • Courtney H. Fox
    • 1
  • Luo Luo Zheng
    • 2
  • Dale J. Waters
    • 1
  • Jennifer R. Cochran
    • 2
  • Christopher N. Ta
    • 3
  • Curtis W. Frank
    • 1
  1. 1.Department of Chemical EngineeringStanford UniversityStanfordUSA
  2. 2.Department of BioengineeringStanford UniversityStanfordUSA
  3. 3.Department of OphthalmologyStanford UniversityStanfordUSA

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