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Bioengineered in vitro model of retinal pigmented epithelium of human eye

No.: 2016/23/Z/ST8/04375
Program: UNISONO
Financing unit: NCN (National Science Center)
Project leader: professor Wojciech Święszkowski
Function: consortium member
Timeframe: 2017 - 2020

Project description

Age-Related Macular Degeneration (AMD) is the leading cause of blindness in the elderly worldwide: although it does not cause total blindness, there is a progressive loss of high-acuity vision attributable to degenerative and neovascular changes in the macula. Currently, there is neither a cure nor a means to prevent AMD. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events and biochemical processes associated with early AMD and the ageing process in general. Although we do have a basic understanding of some of the processes involved in extra-cellular ageing, what comes first and what triggers what is still unclear. Four key phenomena are known to contribute to extracellular senescence: matrix stiffening due to cross-linking and fibrosis, a shift in the reactive oxygen species (ROS) generation/scavenging balance, neovascularization and inflammation. The main objective of BIOMEMBRANE project is the design and fabrication of an alternative and smart in vitro model to boost the discovery of new therapeutic strategies for age-related macular degeneration. The development of an in vitro model of retinal pigmented epithelium (RPE) interfaced to choroidal vascular network (CVN) is expected to provide a more reliable device for the pharmaceutical testing and the evaluation of custom therapies for each patient. This device, developed during the project, will have an important impact on health care costs as the new materials and the related in vitro models are expected to be more economic than the current testing system. To reach the goal, BIOMEMBRANE project will make use of innovative micro- and nano-fabrication system with bioactive materials to mimic the physiological role played by the Bruch’s membrane (BrM), the interface between CVN and RPE. Not only efficacy, standardisation and biocompatibility will be considered, but also the fidelity to reproduce the interface between RPE and the underlying vascular network, as most oxygen and nutrient supply to the outer retina is provided by the choroid. To mimic the topology of this eye structure two different micro and nanofabrication techniques will be combined. The BrM will be assembled using an electrospinning system able to produce an unwoven structure made of fibre with nanometers resolution and with a well-defined porosity at micro and nano level: this structure will be able to mimic the extracellular matrix (ECM) topology, which in turn affects the permeability of this cell-free barrier. The CVN will be designed as a branched microfluidic network, which will be fabricated using a soft lithographic approach. The bioactivity of the bioengineered structures will be improved with SOFT-MI method, by imprinting bioactive sites able to bond selectively selected biomolecules for enhancing cell functions. The cellularized bioengineered RPE and CVN substitutes will be integrated in a unique milli-structure, of the same size of a classic well for cell culture and connected to a peristaltic pump, to be the first biomimetic and dynamic in vitro model of this barrier. The concept of smart multiscale biostructures integrated in a bioengineered platform able to mimic eye’s structures, such as that we will create in BIOMEMBRANE project, will render the European biomaterials, pharmaceutical and biotechnological industries more productive and dynamic. At present these industries are struggling with regulatory issues, due to the fact that their products must comply with stringent pre-clinical testing requirements. Here we propose a novel biotechnological platform aimed at reducing experimental time and costs by mimicking a physiopathological environment difficult to analyse in vivo and develop custom in vitro tests for drug therapy efficacy.