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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

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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1. WHO. Chronic Diseases and Health Promotion, World Health Organisation, 2017. Available from: http://www.who.int/chp/en/.

2. R. E. Maclaren, R. A. Pearson, A. Macneil, R. H. Douglas, T. E. Salt, M. Akimoto, et al., Retinal repair by transplantation of photoreceptor precursors, Nature, 444 (2006), 203-207.

3. M. H. Amer, F. R. A. J. Rose, K. M. Shakesheff, M. Modo, L. J. White, Translational considerations in injectable cell-based therapeutics for neurological applications: Concepts, progress and challenges, npj Regen. Med., 2 (2017), 23.

4. J. Steinbeck, L. Studer, Moving stem cells to the clinic: Potential and limitations for brain repair. HHS Public Access, 86 (2015), 1922-2013.

5. D. P. Schmidt, I. Nouar, P. K. Senecal, J. Rutland, J. K. Martin, R. D. Reitz, et al., Pressure-swirl atomization in the near field, SAE Trans., 108 (1999), 471-484.

6. H. C. Geijssen, Studies on Normal Pressure Glaucoma, Kugler Publications, 1991.

7. S. Singhal, B. Bhatia, H. Jayaram, S. Becker, M. F. Jones, P. B. Cottrill, et al., Human muller glia with stem cell characteristics differentiate into retinal ganglion cell (RGC) precursors in vitro and partially restore RGC function in vivo following transplantation, Stem Cells Transl. Med., 1 (2012), 188-99.

8. A. T. Hafez, D. J. Bagli, A. Bahoric, K. Aitken, C. R. Smith, D. Herz, et al., Aerosol transfer of bladder urothelial and smooth muscle cells onto demucosalized colonic segments: A pilot study, J. Urol., 169 (2003), 2316-2320.

9. A. Roberts, B. E. Wyslouzil, L. Bonassar, Aerosol delivery of mammalian cells for tissue engineering, Biotechnol. Bioeng., 91 (2005), 801-807.

10. M. Cohen, A. Bahoric, H. M. Clarke, Aerosolization of epidermal cells with fibrin glue for the epithelialization of porcine wounds with unfavorable topography, Plast. Reconstr. Surg., 107 (2001), 1208-1215.

11. A. A. Foster, L. M. Marquardt, S. C. Heilshorn, The diverse roles of hydrogel mechanics in injectable stem cell transplantation, Curr. Opin. Chem. Eng., 15 (2017), 15-23.

12. A. Bahoric, A. R. Harrop, H. M. Clarke, R. M. Zuker, Aerosol vehicle for delivery of epidermal cells-An in vitro study, Can. J. Plast. Surg., 5 (1997), 153-156.

13. G. Marx, Evolution of fibrin glue applicators, Transfus. Med. Rev., 17 (2003), 287-298.

14. S. S. Chaurasia, R. Champakalakshmi, R. I. Angunawela, D. T. Tan, J. S. Mehta, Optimization of fibrin glue spray systems for ophthalmic surgery, Transl. Vis. Sci. Technol., 1 (2012), 2.

15. H. Jayaram, S. Becker, K. Eastlake, M. F. Jones, D. G. Charteri, G. A. Limb, Optimized feline vitrectomy technique for therapeutic stem cell delivery to the inner retina, Vet. Ophthalmol., 17 (2014), 300-304.

16. V. Falanga, S. Iwamot, M. Chartier, T. Yufit, J. Butmarc, N. Kouttab, et al., Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds, Tissue Eng., 13 (2007), 1299-1312.

17. R. S. Kirsner, W. A. Marston, R. J. Snyder, T. D. Lee, D. I. Cargill, H. B. Slade, Spray-applied cell therapy with human allogeneic fi broblasts and keratinocytes for the treatment of chronic venous leg ulcers: A phase 2, multicentre, double-blind, randomised, placebo-controlled trial, Lance, 380 (2012), 977-985.

18. A. L. Thiebes, S. Albers, C. Klopsch, S. Jockenhoevel, C. G. Cornelissen, Spraying respiratory epithelial cells to coat tissue-engineered constructs, Bio. Res. Open Access, 4 (2015), 278-287.

19. I. Abu-Reesh, F. Kargi, Biological responses of hybridoma cells to defined hydrodynamic shear stress, J. Biotechnol., 9 (1989), 167-178.

20. A. Hamon, J. E. Roger, X. J. Yang, M. Perron, Müller glial cell-dependent regeneration of the neural retina: An overview across vertebrate model systems, Dev. Dyn. 245 (2016), 727-738.

21. S. Becker, H. Jayaram, G. A. Limb, Recent advances towards the clinical application of stem cells for retinal regeneration, Cells, 1 (2012), 851-873.

22. Y. Li, H. Meng, Y. Liu, B. P. Lee, Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue engineering, Sci. World J., 2015 (2015), 685690.

23. H. Gross, F. Blechinger, B. Achnter, Human eye, in Handbook of Optical Systems, WILEY‐VCH, (2008), 3-20.

24. J. Flammer, S. Orgül, Optic nerve blood-flow abnormalities in glaucoma, Prog. Retin. Eye Res., 17 (1998), 267-289.

25. K. Dijkstra, J. Hendriks, M. Karperien, L. A. Vonk, D. B. E. Saris, Arthroscopic airbrush-assisted cell spraying for cartilage repair: Design, development, and characterization of custom-made arthroscopic spray nozzles, Tissue Eng. Part C Methods, 23 (2017), 505-515.

26. A. H. Lefebvre, V. G. McDonell, Atomization and Sprays, (ed. N. Chigier), 2nd edition, Boca Raton: Taylor & Francis Group, CRC Press, 2017, 1-13.

27. C. X. Bai, H. Rusche, A. D. Gosman, Modelling of gasoline spray impingement, Atomization Sprays, 12 (2002), 1-27.

28. J. M. Lawrence, S. Singhal, B. Bhatia, D. J. Keegan, T. A. Reh, P. J. Luthert, et al,. MIO-M1 cells and similar müller glial cell Lines derived from adult human retina exhibit neural stem cell characteristics, Stem Cells, 25 (2007), 2033-2043.

29. A. T. HAFEZ, K. AFSHAR, D. J. BÄGLI, A. Bahoric, K. Aitken, C. R. Smith, et al., Aerosol transfer of bladder urothelial and smooth muscle cells onto demucosalized colonic segments for porcine bladder augmentation in vivo: A 6 week experimental study, J. Urol., 174 (2005), 1663-1668.

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