Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation

Li, Fengfu and Carlsson, David and Lohmann, Chris and Suuronen, Erik and Vascotto, Sandy and Kobuch, Karin and Sheardown, Heather and Munger, Rejean and Nakamura, Masatsugu and Griffith, May (2003) Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 100 (26). pp. 15346-15351. ISSN 0027-8424

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Abstract

Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required.

Item Type: Article
Uncontrolled Keywords: IN-VITRO; PENETRATING KERATOPLASTY; EPITHELIAL-CELLS; OCULAR SURFACE; RABBIT; SENSITIVITY; MICROSCOPY; BLINDNESS; ADHESION; GLUCOSE; regenerative medicine; tissue engineering; cornea; implantation; innervation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Augenheilkunde
Depositing User: Dr. Gernot Deinzer
Date Deposited: 27 Jul 2021 09:44
Last Modified: 27 Jul 2021 09:44
URI: https://pred.uni-regensburg.de/id/eprint/38305

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