Special Issue "Corneal Scarring: Wound Healing and Biomaterials"

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A special issue of Journal of Functional Biomaterials (ISSN 2079-4983).

Deadline for manuscript submissions: closed (31 August 2012)

Special Issue Editor

Guest Editor
Dr. Dimitris Karamichos

Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston MA 02114, USA
Website | E-Mail
Interests: corneal wound healing; extracellular matrix; biomaterials; growth factors

Special Issue Information

Dear Colleagues,

Over 10 million people worldwide are blind as a result of corneal opacity or scarring. Currently, there are few therapeutic options other than corneal transplantation. One of the hopes for treatment of these patients is the development of an artificial cornea or a compatible biomaterial to replace part or all of the affected area. For well over 200 years, ophthalmologists have been intrigued by the concept of replacing an opaque cornea with an optically clear substitute. These efforts have been slowed by the difficulty in finding a substitute that can replace the exquisitely aligned collagen matrix of the cornea, as well as resist rejection. Several investigations have been made in to the use of plastics to develop an artificial cornea, also termed keratoprosthesis. These keratoprosthesis have enjoyed some success however have not solved the problem. As an alternative to the use of plastics, several investigations have been made to engineer an artificial cornea using natural compounds such as collagens, and to allow corneal cells to secrete their own matrix. The goal of these studies is to develop a synthetic cornea that mimics the native cornea and also integrates into the human eye. It is clearly a huge challenge and the input and effort of various scientific disciplines is vital.

Dr. Dimitris Karamichos
Guest Editor

Keywords

  • cornea
  • scarring
  • wound healing
  • extracellular matrix
  • biomechanics
  • biomaterials
  • keratocytes

Published Papers (5 papers)

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Research

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Open AccessArticle Novel in Vitro Model for Keratoconus Disease
J. Funct. Biomater. 2012, 3(4), 760-775; doi:10.3390/jfb3040760
Received: 29 August 2012 / Revised: 9 October 2012 / Accepted: 24 October 2012 / Published: 13 November 2012
Cited by 11 | PDF Full-text (6495 KB) | HTML Full-text | XML Full-text
Abstract
Keratoconus is a disease where the cornea becomes cone-like due to structural thinning and ultimately leads to compromised corneal integrity and loss of vision. Currently, the therapeutic options are corrective lenses for early stages and surgery for advanced cases with no in vitro
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Keratoconus is a disease where the cornea becomes cone-like due to structural thinning and ultimately leads to compromised corneal integrity and loss of vision. Currently, the therapeutic options are corrective lenses for early stages and surgery for advanced cases with no in vitro model available. In this study, we used human corneal fibroblasts (HCFs) and compared them to human Keratoconus fibroblasts (HKCs) cultured in a 3-dimensional (3D) model, in order to compare the expression and secretion of specific extracellular matrix (ECM) components. For four weeks, the cells were stimulated with a stable Vitamin C (VitC) derivative ± TGF-β1 or TGF-β3 (T1 and T3, respectively). After four weeks, HKCs stimulated with T1 and T3 were significantly thicker compared with Control (VitC only); however, HCF constructs were significantly thicker than HKCs under all conditions. Both cell types secreted copious amounts of type I and V collagens in their assembled, aligned collagen fibrils, which increased in the degree of alignment upon T3 stimulation. In contrast, only HKCs expressed high levels of corneal scarring markers, such as type III collagen, which was dramatically reduced with T3. HKCs expressed α-smooth muscle actin (SMA) under all conditions in contrast to HCFs, where T3 minimized SMA expression. Fast Fourier transform (FFT) data indicated that HKCs were more aligned when compared to HCFs, independent of treatments; however, HKC’s ECM showed the least degree of rotation. HKCs also secreted the most aligned type I collagen under T3 treatment, when compared to any condition and cell type. Overall, our model for Keratoconus disease studies is the first 3D in vitro tissue engineered model that can mimic the Keratoconus disease in vivo and may be a breakthrough in efforts to understand the progression of this disease. Full article
(This article belongs to the Special Issue Corneal Scarring: Wound Healing and Biomaterials)
Open AccessArticle Experimental Models for Investigating Intra-Stromal Migration of Corneal Keratocytes, Fibroblasts and Myofibroblasts
J. Funct. Biomater. 2012, 3(1), 183-198; doi:10.3390/jfb3010183
Received: 27 January 2012 / Revised: 10 March 2012 / Accepted: 13 March 2012 / Published: 19 March 2012
Cited by 3 | PDF Full-text (2425 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Following laser vision correction, corneal keratocytes must repopulate areas of cell loss by migrating through the intact corneal stroma, and this can impact corneal shape and transparency. In this study, we evaluate 3D culture models for simulating this process in vitro. Buttons
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Following laser vision correction, corneal keratocytes must repopulate areas of cell loss by migrating through the intact corneal stroma, and this can impact corneal shape and transparency. In this study, we evaluate 3D culture models for simulating this process in vitro. Buttons (8 mm diameter) were first punched out of keratocyte populated compressed collagen matrices, exposed to a 3 mm diameter freeze injury, and cultured in serum-free media (basal media) or media supplemented with 10% FBS, TGFb1 or PDGF BB. Following freeze injury, a region of cell death was observed in the center of the constructs. Although cells readily migrated on top of the matrices to cover the wound area, a limited amount of cell migration was observed within the constructs. We next developed a novel “sandwich” model, which better mimics the native lamellar architecture of the cornea. Using this model, significant migration was observed under all conditions studied. In both models, cells in TGFb and 10% FBS developed stress fibers; whereas cells in PDGF were more dendritic. PDGF stimulated the most inter-lamellar migration in the sandwich construct. Overall, these models provide insights into the complex interplay between growth factors, cell mechanical phenotypes and the structural properties of the ECM. Full article
(This article belongs to the Special Issue Corneal Scarring: Wound Healing and Biomaterials)

Review

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Open AccessReview Extracellular Matrix is an Important Component of Limbal Stem Cell Niche
J. Funct. Biomater. 2012, 3(4), 879-894; doi:10.3390/jfb3040879
Received: 7 September 2012 / Revised: 4 December 2012 / Accepted: 5 December 2012 / Published: 10 December 2012
Cited by 5 | PDF Full-text (241 KB) | HTML Full-text | XML Full-text
Abstract
Extracellular matrix plays an important role in stem cell niche which maintains the undifferentiated stem cell phenotype. Human corneal epithelial stem cells are presumed to reside mainly at the limbal basal epithelium. Efforts have been made to characterize different components of the extracellular
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Extracellular matrix plays an important role in stem cell niche which maintains the undifferentiated stem cell phenotype. Human corneal epithelial stem cells are presumed to reside mainly at the limbal basal epithelium. Efforts have been made to characterize different components of the extracellular matrix that are preferentially expressed at the limbus. Mounting evidence from experimental data suggest that these components are part of the stem cell niche and play a role in the homeostasis of limbal stem cells. The extracellular matrix provides a mechanical and structural support as well as regulates cellular functions such as adhesion, migration, proliferation, self-renewal and differentiation. Optimization of the extracellular matrix components might be able to recreate an ex vivo stem cell niche to expand limbal stem cells. Full article
(This article belongs to the Special Issue Corneal Scarring: Wound Healing and Biomaterials)
Open AccessReview Tissue Engineering of Corneal Endothelium
J. Funct. Biomater. 2012, 3(4), 726-744; doi:10.3390/jfb3040726
Received: 27 July 2012 / Revised: 12 September 2012 / Accepted: 17 September 2012 / Published: 17 October 2012
Cited by 6 | PDF Full-text (648 KB) | HTML Full-text | XML Full-text
Abstract
Human corneal endothelial cells (HCECs) do not replicate after wounding. Therefore, corneal endothelial deficiency can result in irreversible corneal edema. Descemet stripping automated endothelial keratoplasty (DSAEK) allows selective replacement of the diseased corneal endothelium. However, DSAEK requires a donor cornea and the worldwide
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Human corneal endothelial cells (HCECs) do not replicate after wounding. Therefore, corneal endothelial deficiency can result in irreversible corneal edema. Descemet stripping automated endothelial keratoplasty (DSAEK) allows selective replacement of the diseased corneal endothelium. However, DSAEK requires a donor cornea and the worldwide shortage of corneas limits its application. This review presents current knowledge on the tissue engineering of corneal endothelium using cultured HCECs. We also provide our recent work on tissue engineering for DSAEK grafts using cultured HCECs. We reconstructed DSAEK grafts by seeding cultured DiI-labelled HCECs on collagen sheets. Then HCEC sheets were transplanted onto the posterior stroma after descemetorhexis in the DSAEK group. Severe stromal edema was detected in the control group, but not in the DSAEK group throughout the observation period. Fluorescein microscopy one month after surgery showed numerous DiI-labelled cells on the posterior corneal surface in the DSAEK group. Frozen sections showed a monolayer of DiI-labelled cells on Descemet’s membrane. These findings indicate that cultured adult HCECs, transplanted with DSAEK surgery, maintain corneal transparency after transplantation and suggest the feasibility of performing DSAEK with HCECs to treat endothelial dysfunction. Full article
(This article belongs to the Special Issue Corneal Scarring: Wound Healing and Biomaterials)
Open AccessReview Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering
J. Funct. Biomater. 2012, 3(3), 642-687; doi:10.3390/jfb3030642
Received: 30 June 2012 / Revised: 27 August 2012 / Accepted: 30 August 2012 / Published: 18 September 2012
Cited by 12 | PDF Full-text (2228 KB) | HTML Full-text | XML Full-text
Abstract
Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due
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Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation. Full article
(This article belongs to the Special Issue Corneal Scarring: Wound Healing and Biomaterials)
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