Abstract
Chronic eye diseases are the main cause of vision loss among adults. Among these, retinal degenerative diseases affect millions of people globally, causing permanent loss of cells and organ dysfunction. Despite recent progress in developing stem cell therapies for retinal diseases, methods for delivery remain an area of intense research. Aerosol technology is a promising technique with the potential to spray cells evenly and directly across the retinal surface, promoting cell attachment and survival. Here we implement mathematical modelling of the spraying process to develop organ-specific spraying parameters in this therapeutic scenario. Firstly, we characterise the rheological parameters for a typical hydrogel used for spraying cells. These parameters are then integrated into a 3D computational model of an adult human eye under realistic surgical conditions. Simulation results provide quantitative relationships between the volume flow rate of the cell-laden hydrogel, external pressure needed for aerosolization, angle of the spraying, and properties of the cell delivery. An experimental assessment is also carried out to explore the impact of spraying under the regimes identified by the computational model on cell viability. This is the first stage towards using computational models to inform the design of spray systems to deliver cell therapies onto the human retina.
Highlights
Chronic degenerative diseases affect millions of people globally [1]; they can cause permanent loss of specialised cells, often resulting in organ dysfunction and degeneration
We present the experimental methods used to characterise the rheological properties of the hydrogels used for spraying, followed by the computational model used to describe spraying of cell-laden hydrogels in the human eye, and the experimental methods used to assess cell viability under different spraying conditions
We model the spraying of a cellular suspension, comprised of stem cells embedded in fibrin-derived gel, onto the inner surface of the human retina
Summary
Chronic degenerative diseases affect millions of people globally [1]; they can cause permanent loss of specialised cells, often resulting in organ dysfunction and degeneration. This spraying technology relies on aerosolization to deliver a controlled volume of cellular hydrogel in droplet form; commercially available spraying applicators (for example, Baxter [13]) have integrated pressure regulators and nozzle adaptors to enable the volume, pressure and flow rate of the cellular scaffold to be controlled to cover a required surface area of tissue with a spatially uniform cell layer This technology has been subsequently used both preclinically and clinically, including on animal eye models [14,15], human cutaneous wounds and ulcers [16,17] and for tracheal tissue engineering [18]. Sensitivity analyses of the model predictions demonstrate the link between key parameters (such as air pressure, volumetric flow rates) and features of the spray that must be controlled (such as retinal surface area to be covered, thickness of the cell layer, velocity of sprayed droplets) These relationships are formulated as operating equations, which enable an end-user to define spraying parameters to achieve geometry-specific outcomes. This is the first stage towards using computational models to inform the design of spray systems to deliver cell therapies onto the human retina
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