Biomicrofluidics: understanding deep vein thrombosis and controlling cells behaviour

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• Dr Daniele Vigolo, University of Birmingham
• Thursday 10 October 2019, 11:00-12:00
• Department of Chemistry, Unilever Lecture Theatre.

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In my talk I will discuss the exploitation of microfluidics in biomedical applications. I will focus in particular on two topics: the possibility to investigate the mechanisms of thrombus formation in deep vein thrombosis (DVT) and an innovative method to control cells behaviour by introducing mechanical cues within the soft biocompatible substrate where cells are grown taking advantage of thermophoresis. In the first part of my talk I will introduce DVT , which is a dangerous and painful condition in which blood clots form in deep veins (e.g. femoral vein¹). Mechanisms of clot development remain unclear, however the specific flow patterns in veins, especially around the valve flaps play a fundamental role². In order to study DVT , we fabricated flexible valves made of polyethylene glycol diacrylate (PEGDA) in-situ in a microfluidic device achieving control over geometry and elasticity using stop flow lithography³. By tuning PEGDA and photoinitiator concentration we independently varied the elasticity of each valve’s leaflet in order to obtain symmetrical or asymmetrical characteristics. To analyse the velocity profiles we exploit ghost particle velocimetry (GPV) [4,5] and we studied particle accumulation, mimicking clot formation, by flowing polystyrene particles. Here I will show the results we obtained showing that elasticity of the valves and flow conditions are important factors when looking at clot formation in DVT as they will influence residence time behind the valve and thus increase likelihood of thrombus formation and this is important as a major risk factor for DVT in the elderly is a reduced elasticity of their valves. In the second part of my talk I will discuss the optimisation of the interactions between cells and the material over which they are cultivated, important for tissue engineering and biomedical applications such as tissue repair and wound healing. In particular I will focus on biomaterials exhibiting a gradient of mechanical properties that can be used to regulate cell behaviour [6,7]. However, the possibility to create these materials is still limited especially at the micron scale [8]. Here I will show that by carefully imposing and controlling temperature gradients across a microfluidic channel and exploiting thermophoresis [9,10], we can induce gradients of stiffness in a biocompatible hydrogel [11]. A microfluidic device consisting of a main microchannel and two side channels acting as hot and cold thermal sources [12] are used to apply the transversal temperature gradient and fabricate biocompatible hydrogels exhibiting a stiffness gradient. We characterised the biomaterials by evaluating locally the Young’s modulus by AFM nanoindentation, and their porosity by Scanning Electron Microscopy (SEM). Finally, we monitored the cells behaviour over time by seeding MC3T3 osteoblasts on the surface of the biomaterial. Selective cell viability, migration and mineralisation of the substrate were observed.

References 1 Hunt, B. J. Br. J. Haematol. 144, 642–652 (2009) 2 Bovill, E. G. et al. Annu. Rev. Physiol. 73, 527–545 (2011) 3 Wexler, J. S. et al. J. Fluid Mech. 720, 517–544 (2013) 4 Buzzaccaro, S. et al. Phys. Rev. Lett. 111, 048101 (2013) 5 Riccomi, M. et al. Chem. Eng. Res. Des. 133, 183–194 (2018) 6 Moreo, P. et al. Acta Biomater. 4, 613–21 (2008) 7 Hsiong, S. X. et al. J. Biomed. Mater. Res. A 85 , 145–56 (2008) 8 Vincent, L. G. et al. Biotechnol. J. 8, 472–484 (2013) 9 Vigolo, D. et al. Soft Matter 6, 3489 (2010) 10 Vigolo, D. et al. Langmuir 26, 7792–801 (2010) 11 Vigolo, D. et al. Sci. Rep. 9, 7125 (2019) 12 Vigolo, D. et al. Sci. Rep. 7, 1211 (2017)

This talk is part of the Biophysical Seminar series.

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