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Design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct

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Abstract

We describe the design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct, and demonstrate the adhesion of corneal epithelial and fibroblast cells to its central and peripheral components, respectively. The design consists of a central “core” optical component and a peripheral tissue-integrable “skirt.” The core is composed of a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) double-network with high strength, high water content, and collagen type I tethered to its surface. Interpenetrating the periphery of the core is a microperforated, but resilient poly(hydroxyethyl acrylate) (PHEA) hydrogel skirt that is also surface-modified with collagen type I. The well-defined microperforations in the peripheral component were created by photolithography using a mask with radially arranged chrome discs. Surface modification of both the core and skirt elements was accomplished through the use of a photoreactive, heterobifunctional crosslinker. Primary corneal epithelial cells were cultured onto modified and unmodified PEG/PAA hydrogels to evaluate whether the central optic material could support epithelialization. Primary corneal fibroblasts were seeded onto the PHEA hydrogels to evaluate whether the peripheral skirt material could support the adhesion of corneal stromal cells. Cell growth in both cases was shown to be contingent on the covalent tethering of collagen. Successful demonstration of cell growth on the two engineered components was followed by fabrication of core-skirt constructs in which the central optic and peripheral skirt were synthesized in sequence and joined by an interpenetrating diffusion zone.

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Acknowledgments

This research was supported by the Bio-X Program and the Office of Technology Licensing at Stanford University. Instrument support was provided by the shared facilities at the Center on Polymer Interfaces and Macromolecular Assemblies (CPIMA) at Stanford University. The authors thank Stacey Bent and Jungsic Hong for use of the X-ray spectrometer and Beinn Muir for use of his high-resolution digital camera. Additional external support was also received from VISX, Incorporated (now VISX Technology) and the Fight for Sight Foundation.

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Authors and Affiliations

  1. Department of Ophthalmology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305-5080, USA

    David Myung, Amit Bakri, Jaan Noolandi & Christopher N. Ta

  2. Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stauffer III, Stanford, CA, 94305, USA

    David Myung, Amanda Marshall, Jungmin Ko, Jaan Noolandi & Curtis W. Frank

  3. Department of Chemical Engineering, Yonsei University, 134 Shinchon-dong, Seodaemoon-ku, Seoul, 120-749, South Korea

    Wongun Koh

  4. Department of Bioengineering, Stanford University, 318 Campus Drive, Clark Center, Stanford, CA, 94305, USA

    Fan Zhang & Jennifer R. Cochran

  5. Department of Chemistry, Santa Clara University, 500 El Camino Real, Santa Clara, California, 95053, USA

    Michael Carrasco

  6. Department of Ophthalmology, Stanford University, 900 Blake Wilbur Drive, W3036, Stanford, CA, 94304-5353, USA

    Christopher N. Ta

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  1. David Myung
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  2. Wongun Koh
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  11. Christopher N. Ta
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Correspondence to Christopher N. Ta.

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Myung, D., Koh, W., Bakri, A. et al. Design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct. Biomed Microdevices 9, 911–922 (2007). https://doi.org/10.1007/s10544-006-9040-4

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