The Network of Excellence in Corneal Regeneration

2016 Research Articles

Lynch AP, Wilson SL, Ahearne M. Dextran Preserves Native Corneal Structure

During Decellularization. Tissue Eng Part C Methods. 2016 Jun;22(6):561-72.




Tóth G, Bucher F, Siebelmann S, Bachmann B, Hermann M, Szentmáry N, Nagy ZZ, Cursiefen C. In Situ Corneal Cross-Linking for Recurrent Corneal Melting After Boston Type 1 Keratoprosthesis. Cornea. 2016 Jun;35(6):884-7.




Schaub F, Hos D, Bucher F, Siebelmann S, Bachmann BO, Cursiefen C. [Boston-keratoprosthesis : Preliminary experiences in 13 high-risk eyes from the Department of Ophthalmology of the University of Cologne]. Ophthalmologe. 2016 Jun;113(6):492-9.




Morgado AL, Rodrigues CM, Solá S. MicroRNA-145 Regulates Neural Stem Cell Differentiation Through the Sox2-Lin28/let-7 Signaling Pathway. Stem Cells. 2016 May;34(5):1386-95.




Kumar P, Pandit A, Zeugolis DI. Progress in Corneal Stromal Repair: From Tissue Grafts and Biomaterials to Modular Supramolecular Tissue-Like Assemblies. Adv Mater. 2016 Mar 30.




Siebelmann S, Steven P, Hos D, Hüttmann G, Lankenau E, Bachmann B, Cursiefen C. Advantages of microscope-integrated intraoperative online optical coherence tomography: usage in Boston keratoprosthesis type I surgery. J Biomed Opt. 2016 Jan;21(1):16005.





Notara M, Refaian N, Braun G, Steven P, Bock F, Cursiefen C. Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu. Invest Ophthalmol Vis Sci. 2016 Mar 1;57(3):928-39.






Barbaro V, Nasti AA, Raffa P, Migliorati A, Nespeca P, Ferrari S, Palumbo E, Bertolin M, Breda C, Miceli F, Russo A, Caenazzo L, Ponzin D, Palù G, Parolin C, Di Iorio E. Personalized Stem Cell Therapy to Correct Corneal Defects Due to a Unique Homozygous-Heterozygous Mosaicism of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome. Stem Cells Transl Med. 2016 May 5.






Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications
Mehrdad Rafat, Maria Xeroudaki, Marina Koulikovska, Peter Sherrell, Fredrik Groth, Per Fagerholm, Neil Lagali

Article history: Received 4 June 2015; Received in revised form; 24 December 2015; Accepted 1 January 2016; Available online 4 January 2016



Scarcity of donor tissue to treat corneal blindness and the need to deliver stem cells or pharmacologic agents to ensure corneal graft survival are major challenges. Here, new composite collagen-based hydrogels are developed as implants to restore corneal transparency while serving as a possible reservoir for cells and drugs. The composite hydrogels have a centrally transparent core and embedded peripheral skirt of adjustable transparency and degradability, with the skirt exhibiting faster degradation in vitro. Both core and skirt supported human epithelial cell populations in vitro and the skirt merged homogeneously with the core material to smoothly distribute a mechanical load in vitro. After in vivo transplantation in rabbit corneas over three months, composites maintained overall corneal shape and integrity, while skirt degradation could be tracked in vivo and non-invasively due to partial opacity. Skirt degradation was associated with partial collagen breakdown, thinning, and migration of host stromal cells and macrophages, while the central core maintained integrity and transparency as host cells migrated and nerves regenerated.

Impact: This study indicates the feasibility of a collagen-based composite hydrogel to maintain corneal stability and transparency while providing a degradable peripheral reservoir for cell or substance release.
© 2016 Elsevier Ltd. All rights reserved.






Biocompatibility of a fish scale-derived artificial cornea: Cytotoxicity, cellular adhesion and phenotype, and in vivo immunogenicity.

van Essen TH1, van Zijl L2, Possemiers T3, Mulder AA4, Zwart SJ5, Chou CH6, Lin CC7, Lai HJ8, Luyten GP9, Tassignon MJ10, Zakaria N11, El Ghalbzouri A12, Jager MJ13


Biomaterials. 2016 Mar;81:36-45. doi: 10.1016/j.biomaterials.2015.11.015. Epub 2015 Dec 1.




To determine whether a fish scale-derived collagen matrix (FSCM) meets the basic criteria to serve as an artificial cornea, as determined with in vitro and in vivo tests.


Primary corneal epithelial and stromal cells were obtained from human donor corneas and used to examine the (in)direct cytotoxicity effects of the scaffold. Cytotoxicity was assessed by an MTT assay, while cellular proliferation, corneal cell phenotype and adhesion markers were assessed using an EdU-assay and immunofluorescence. For in vivo-testing, FSCMs were implanted subcutaneously in rats. Ologen(®) Collagen Matrices were used as controls. A second implant was implanted as an immunological challenge. The FSCM was implanted in a corneal pocket of seven New Zealand White rabbits, and compared to sham surgery.


The FSCM was used as a scaffold to grow corneal epithelial and stromal cells, and displayed no cytotoxicity to these cells. Corneal epithelial cells displayed their normal phenotypical markers (CK3/12 and E-cadherin), as well as cell-matrix adhesion molecules: integrin-α6 and β4, laminin 332, and hemi-desmosomes. Corneal stromal cells similarly expressed adhesion molecules (integrin-α6 and β1). A subcutaneous implant of the FSCM in rats did not induce inflammation or sensitization; the response was comparable to the response against the Ologen(®) Collagen Matrix. Implantation of the FSCM in a corneal stromal pocket in rabbits led to a transparent cornea, healthy epithelium, and, on histology, hardly any infiltrating immune cells.


The FSCM allows excellent cell growth, is not immunogenic and is well-tolerated in the cornea, and thus meets the basic criteria to serve as a scaffold to reconstitute the cornea.

KEYWORDS: Artificial cornea; Biocompatibility; Collagen; In vitro; In vivo; Keratoprosthesis




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Action BM1302 "Joining Forces in Corneal Regeneration Research" 2014-2017.