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Miriam Nweze, Tim Baker, Astrid Limb, Rebecca J Shipley; Computational modelling as a tool to accelerate designs of spray systems for cell-based therapies to treat retinal diseases. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5006.
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Recently there has been significant progress in developing stem cells therapies to treat retinal diseases.Suitable methods for transplantation are still a subject of research.We used computational modelling to define spraying parameters for aerosol systems,to simulate delivery of stem cells onto the inner retinal surface.
We mimicked the geometry of the human eye using a 25 mm diameter hemisphere. We used computational fluid dynamics(implemented and solved using a finite element package)to simulate spraying of cells suspended in a hydrogel(modelled using continuum mechanics)and tracked the spatial and temporal distribution of the associated droplets.An injector with a 0.6 mm diameter nozzle was introduced into the simulated eye, and its location and orientation controlled to determine spraying conditions.We predicted the surface area of the retina to be sprayed and the thickness of the film delivered, and examined how to control these parameters through volume flow rate and pressure applied to the injector. We explored volume flow rates between 100 and 400 μL/s,with air pressures between 10 and 100 kPa.
Our simulations indicated that the surface area of the retina could be controlled by specifying the outer cone angle of the sprayed cell suspension, characterised by a linear relationship between the cone angle and the sprayed area (R2 =0.99).We observe a direct relationship between the flow rate, pressure at the nozzle on the overall thickness of the hydrogel layer (R2=0.84).The volume flow rate and pressure at the nozzle could be used to control the overall thickness of the cellular suspension.For example,if we desire a thickness of 1.5 mm,the cellular suspension will be sprayed at 400 μLs-1 at 10 kPa and 300 μLs-1 at 100 kPa.The present observations indicated that simulation protocols may provide a platform to derive specific parameters for the desired overall thickness of cell layers,and could predict the required number of cells needed for each spraying event.
The data provides evidence that cell delivery can be controlled by varying flow rate and pressure;computational modelling can inform the operating conditions for attachment of cells onto the inner surface of the retina.Validation of these methods will require experimental testing ex vivo and in vivo before they can be translated into the clinic and merits further investigations.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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