Research team

Cobioto, Corneale Biopsy Tool. 06/03/2017 - 05/03/2018

Abstract

Keratitis, or an inflammation of the cornea, is a common eye disease in which a biopsy of the cornea is required to determine its underlying cause which can range from infectious causes (including viral, bacterial, fungal, parasitic), mechanical (contact lens wear), non infectious (Vitamin A deficiency) (Gorski et al., 2015). Currently, no standardized tool is available for taking such biopsy and corneal scrapings are performed with a scalpel or wide bore needle, very often with inconclusive results as too little material is removed for fear of penetration. Consequently, biopsies are not performed as often and a broad-spectrum antibiotic is prescribed, assuming bacterial keratitis. The delay in providing optimal treatment can result in untoward sequelae such as corneal scarring and opacification requiring corneal transplantation. Collaborative research between the department of ophthalmology (UZA) Centre for Cell Therapy and Regenerative Medicine (Ophthalmology/Vaxinfectio – UA/UZA) and Product Development (UA) together with the industrial partner D.O.R.C. will lead to the development of a standardized tool for taking a biopsy of the cornea where the safety of the patient is guaranteed thereby addressing the aforementioned shortcomings.

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Tissue engineering in Ophthalmology: Regenerating the Anterior Cornea using Self-Aligning Human Recombinant Collagen nanoscaffolds and Corneal Epithelial Stem Cells. 01/10/2016 - 30/09/2018

Abstract

The overall aim of this project is to develop a scaffold with collagen nanofibre alignment to replace the existing use of human amniotic membranes for ocular surface reconstruction. The expected outcome is a standardized prototype composite graft with improved transparency, mechanical strength, bio-integration and reduced microbial susceptibility, realised through combining biomaterials engineering, protein surface modification and stem cell technologies. During the course of this research we intend to bring this prototype to a proof-of-concept in a rabbit model of limbal stem cell deficiency. This cutting-edge research will lay the groundwork for the development of sustainable biomimetic artificial corneas through an extension of its engineering.

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Tissue Engineering in Ophthalmology: Regenerating the ocular surface using standardized, xeno-free, tissue-engineered conjunctival grafts for conjunctival reconstruction. 01/10/2016 - 30/09/2017

Abstract

The conjunctiva is a thin membrane, which covers the white part of the eye and the inside of the eyelids. It is essential that this membrane functions correctly as it plays an important role in the maintenance of a healthy ocular surface and the preservation of vision. In some ocular disorders, the conjunctiva is damaged resulting in excessive scarring leading to surface disorders such as severe dry eyes, eyelid distortions and even blindness. Current treatment strategies for conjunctival reconstruction include surgically removing the diseased tissue and placing a human amniotic membrane over the bare sclera to aid in tissue regeneration. However, at times, either due to the nature of the diseased environment or a lack of properly functioning conjunctival epithelial stem cells, there is aberrant wound healing with scar formation, worsening the outlook for ocular reconstruction. In this project, we address this issue by creating a cellularized conjunctival substitute that can be transplanted onto the ocular surface after debridement of diseased tissue. This substitute is expected to reduce/eliminate scar formation and facilitate regeneration by providing a functional conjunctival replacement, containing both mucin-producing goblet cells to stabilize the tear film as well as conjunctival epithelium to establish a barrier to infectious microbes. The human amniotic membrane will be investigated as a biological scaffold for cultivating the cellular grafts for this purpose.

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Research team(s)

From bench to bedside: accelerating the clinical development of cell therapy innovations by "lean" gmp manufacturing of ATMP. 01/05/2016 - 30/11/2016

Abstract

To specifically advance translation initiatives of cell therapeutic advanced therapeutic medicinal products (ATMP) into commercially viable and safe treatments and hence, overcome regulatory, developer-related and value chain-related challenges, a consortium of stakeholders along the value chain, will, in collaboration with the sponsor, drive the ATMP through the early clinical trials with the objective to generate a lean manufactured and effective ATMP. The key concept is to task each of the specific necessary steps to the entity that is best suited for the task. It is important for all team members to understand, to some degree, the whole process involved in product development to adequately balance what needs to be done and more importantly when to do it as time and resources are not unlimited. Concrete tasks of this partnership are (i) upgrade the research 'product and process' to a lean manufacturing process with built-in quality measures, (ii) revise the whole process to generate an efficient, scalable process from patient to lab and back to patient, (iii) interact from an early stage with the Committee for Advanced Therapies (CAT) in the process of marketing authorization licensing and (iv) will support the sponsor in the licensing/spin-out of their ATMP project. In collaboration with an external consultant, different business models will be evaluated from which one concrete business case will be designed and serve as the basis to apply for further funding.

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    Development of a biocompatible corneal endothelial cell based therapy to address global corneal donor shortage. 01/01/2016 - 31/12/2019

    Abstract

    Human corneal endothelial cells (HCEnC) regulate fluid and solute transport across the posterior surface of the human cornea and actively maintain the cornea in a dehydrated state, which is crucial for optical transparency.The dual function of the corneal endothelium is described as the "pump-leak hypothesis" which is essential to allow nutrition to the cornea whilst maintaining its avascularity and transparency. There is no evidence that human endothelial cells divide under normal circumstances as they are arrested in G1 phase of the cell cycle, although they can be induced to divide in vitro. When the amount of corneal endothelial cells decreases below a certain threshold, this cell layer can no longer pump sufficient fluid back to the anterior chamber, resulting in an irreversibly swollen, cloudy cornea. Despite its success, corneal transplantation (either full-thickness or partial) is limited worldwide by the shortage of suitable donor corneas incurring long waiting times. Initial progress to overcome this global shortage is the use of one donor cornea for multiple partial keratoplasties ("split-cornea transplantations"), by using one donor cornea for a partial endothelial and a stromal transplantation. This project aims to investigate ex vivo expansion of corneal endothelial cells to develop a cell sheet based therapy. This would overcome donor deficit that limits the treatment of corneal endotheliopathies. The principle is to expand primary human corneal endothelial cells isolated from human cadavers and to seed them on an ideal scaffolding material to introduce these cells in the patient. Specifically in this project we propose the expansion of human corneal endothelial cells (HCEnC) on human lens capsules to obtain a composite graft. The final goal of this project is a proof-of-principle of this functional cell sheet in a rabbit corneal endotheliopathy model.

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    REGENERATing the cornEa : REGENERATE (Euronanomed II part of ERA-NET scheme) 01/04/2015 - 31/03/2018

    Abstract

    This is a fundamental research project financed by the Research Foundation – Flanders (FWO). The project was subsidized after selection by the FWO-expert panel.The human cornea is transparent and depends on this property to allow vision. Damage to the stem cell population that maintains the cornea surface results in Limbal Epithelial Stem Cells Deficiency (LSCD). This results in conjunctival overgrowth of the cornea with stromal scarring, corneal neovascularisation and opacification with decreased visual acuity, pain and photophobia. Current surgical treatment for LSCD includes transplanting large segments of donor excised limbal tissue but has a high risk of complications. Recent research has shown the benefit and feasibility of small limbal grafts cultured on biologically-derived scaffolds, e.g. human amniotic membranes. However, these are optically translucent at best. Being biologically derived they are difficult to standardise and carry potential health risks. Our objective, therefore, is to take a multidisciplinary approach to develop a synthetic alternative with superior cell-interactive properties that circumvents the problems with current limbal stem cell delivery scaffolds. Our research strategy is to exploit the recent introduction of human recombinant collagen that displays nano-fibre alignment under shear deposition to develop transparent, mechanically stable nano-implants that mimic the corneal collagen alignment seen in normal, healthy corneas. In order to further enhance cellular attachment, improved delivery and biointegration, the scaffolds will be enhanced through nano-printing of surface peptides. Collectively we will bring this nano-corneal scaffold to a proof-of-principle in animal models of limbal stem cell deficiency. By providing advancements in corneal regeneration we will be able to gain more insight into regenerative medicine as a whole. The data that we will acquire from this research will help us better understand the role that collagen nano-fibre alignment and surface nano-patterning plays in improving implant integration, and survival eventually paving the way to full thickness synthetic corneal replacements in the future. Our expected results include new scaffolds for delivery of stem cells that will have an impact of healthcare, in particular ophthalmology. However, the technologies developed also form a broader nanotechnology base that can be extended to regeneration of other target organs. An IP protection and dissemination strategy will ensure our economic and scientific impacts.

    Researcher(s)

    Research team(s)

    Development of a biomimetic cornea combining additive manufacturing and stem cell technologies. 01/01/2015 - 31/12/2015

    Abstract

    Each year, there are 1.5-2.0 million new cases of monocular corneal blindness due to ocular trauma and corneal ulceration. This includes 500 new cases in Flanders, while only 350 corneal transplants are performed annually. This project aims to develop biomimetic corneal constructs that will be fabricated using 3D printing and which will be seeded with corneal stem cells, which allows cost-effective manufacturing of customized structures with high resolution. This project will focus on innovation via interdisciplinary collaboration between production engineering, biomaterials and cell biology in ophthalmology in order to bring the 3D printed biocornea to a proof-of-concept. The overall goal is to create a biocornea that is optically transparent, with appropriate mechanical and geometric properties that can serve as a replacement for the existing use of cadaveric donor corneas

    Researcher(s)

    Research team(s)

    Tissue engineering in Ophthalmology: Regenerating the Anterior Cornea using Self-Aligning Human Recombinant Collagen nanoscaffolds and Corneal Epithelial Stem Cells. 01/10/2014 - 30/09/2016

    Abstract

    The overall aim of this project is to develop a scaffold with collagen nanofibre alignment to replace the existing use of human amniotic membranes for ocular surface reconstruction. The expected outcome is a standardized prototype composite graft with improved transparency, mechanical strength, bio-integration and reduced microbial susceptibility, realised through combining biomaterials engineering, protein surface modification and stem cell technologies. During the course of this research we intend to bring this prototype to a proof-of-concept in a rabbit model of limbal stem cell deficiency. This cutting-edge research will lay the groundwork for the development of sustainable biomimetic artificial corneas through an extension of its engineering.

    Researcher(s)

    Research team(s)

    Development of a biomimetic cornea combining additive manufacturing and stem cell technologies. 01/01/2014 - 31/12/2017

    Abstract

    The overall goal is to create a bio-cornea that is optically transparent, with appropriate mechanical and geometric properties. Bio-compatability and integration will be determined in in vivo rabbit models of corneal transplantation. This project will focus on innovation via interdisciplinary collaboration between production engineering, biomaterials, and cell biology in ophthalmology in order to bring the 3D printed bio-cornea to a proof-ofconcept.

    Researcher(s)

    Research team(s)