Insights into the design of spray systems for cell therapies for retinal disease using computational modelling

Miriam Nweze; Tim Baker; G. Astrid Limb; Rebecca J. Shipley; Miriam Nweze; Tim Baker; G. Astrid Limb; Rebecca J. Shipley

doi:10.3934/mbe.2020150

Mathematical Biosciences and Engineering

2020, Volume 17, Issue 3: 2741-2759. doi: 10.3934/mbe.2020150

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Research article

Insights into the design of spray systems for cell therapies for retinal disease using computational modelling

1.
Department of Mechanical Engineering, University College London, UK
2.
Institute of Healthcare Engineering, University College London, UK
3.
Institute of Ophthalmology, University College London, UK

Received: 10 October 2019 Accepted: 11 February 2020 Published: 11 March 2020

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.
- computational modelling,
- retina,
- cell-based therapy,
- cell spraying,
- cell delivery
Citation: Miriam Nweze, Tim Baker, G. Astrid Limb, Rebecca J. Shipley. Insights into the design of spray systems for cell therapies for retinal disease using computational modelling[J]. Mathematical Biosciences and Engineering, 2020, 17(3): 2741-2759. doi: 10.3934/mbe.2020150

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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.

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