Biopolymers immobilized on Polyester Membranes: a new vision towards ocular regeneration

Student thesis: Doctoral Thesis

Abstract

Ocular diseases are leading causes of visual impairment in the western society. Although there exists a plethora of conditions, the current PhD research focusses on cornea-related conditions. Over 10 million people worldwide suffer from corneal blindness with a yearly prevalence of 1.5 million.1 One important cause of corneal blindness is related to dysfunction of the corneal endothelium.2 This monolayer of hexagonal cells maintains the cornea in a state of deturgescence via a pump-and-leak mechanism.2 These cells, however, cannot undergo mitosis and consequently do not regenerate. When the monolayer is damaged, they can only migrate and enlarge to cover the tissue defect. Following ageing, trauma or disease, the cell density will drop below a critical threshold and excessive fluid is no longer efficiently pumped away from the cornea, leading to edema. Concomitant loss of the organized collagen structure results in opacity, thereby impairing vision.2 Currently, treatment is only possible through corneal endothelial transplantation, for which tissue is sourced from cadaveric donor eyes. Unfortunately, supply does not meet the demand, thereby underlining the need for tailored synthetic alternatives to develop ex vivo manufactured biomimetic grafts which is the focus of the current PhD research.3 The ideal endothelial graft should be transparent to visual light (> 90%, 390 – 700 nm). It needs to allow the free passage of nutrients and waste (O2, CO2, glucose).4 To this end, a permeability close to or higher than that of the natural Descemet’s membrane and endothelium should be achieved (1.2*10-5 cm/s).5 Since the natural Descemet’s membrane is characterized by a thickness of around 10 µm and currently applied grafts measure up to 120 µm, the proposed membrane should be well below 120 µm and preferably in the same order of magnitude to the natural membrane.6,7 Additionally, it needs to be robust to allow easy handling during surgical procedures, while exhibiting sufficient flexibility in order not to damage the surrounding tissue after implantation. It should also be biocompatible and promote the growth of corneal endothelial cells thereby maintaining the correct cellular phenotype.4 Furthermore, biodegradability is preferred to limit long- term foreign body complications. Finally, the option to introduce active compounds to the membrane including anti-oxidants or pharmaceuticals is considered beneficial. To meet these requirements, a dedicated transparent poly(lactic acid) derived polyester will be developed to provide mechanical support, while gelatin-based coatings will yield a proper extracellular matrix (ECM) mimic. Finally, the influence of micropatterns deposited using two-photon-polymerization, a state-of-the-art microfabrication technique, on cellular behaviour will be assessed. Additionally, the technique allows the introduction of other biomolecules or pharmaceuticals including laminin, fibronectin and RGD sequences to provide a superior ECM mimic.
Date of AwardDec 2019
Original languageEnglish

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