MDR Vacation Bursary Project: Engineering mechanically-defined microenvironments for stem cells
by Luke Goater
By Pernille Fladsrud, undergraduate student, Faculty of Engineering and the Environment
I just completed my third year in Mechanical Engineering at The University of Southampton, and will continue into my last year of a four-year Master of Science (MSc) degree after summer. My degree theme is engineering management, but I have also chosen to focus on bioengineering. This internship project is in collaboration with Dr Nick Evans, in the Centre for Human Development, Stem Cells and Regeneration and the Bioengineering Sciences Group. The field of research for this project is stem cells and wound healing, and how mechanical signals affect cell behaviour and wound healing.
Human adult skin is a heterogeneous tissue, and we’ve been attempting to model its mechanics in vitro. During my third year individual project I worked with Dr. Evans to design an apparatus to fabricate polyacrylamide hydrogel substrates with varying stiffness; i.e. surfaces whose stiffness varied as a function of distance in the x and y directions. We’ve been doing this to find out how stiffness variations affect the way skin cells differentiate, migrate and proliferate over a heterogeneous surface – a particularly important consideration during wound closure. The stiffness variation in the hydrogels was tested applying the method of Atomic Force Microscopy, and force maps were plotted of the various stiffness regions. (Figure 1)
Figure 1: Force maps of the low stiffness and high stiffness region in one single polyacrylamide hydrogel
We found that keratinocyte skin cells migrate to the areas of higher stiffness, which we predicted before the experiments. This can be seen in (Figure 2), where the cells have migrated to higher stiffness stripes in a striped patterned substrate. This Vacation Bursary project has given me the opportunity to further investigate the field of wound healing, and continue my interest within bioengineering.
Figure 2: Patterned hydrogel substrates, after 24 hours of cell culture with keratinocyte skin cells. Cells have preferentially migrated to areas of high stiffness.
At the moment we are investigating how topography alone, or topography in combination with varying stiffness, affects the behaviour of cells. The epithelium of the skin has an undulating topography, and we’re trying to model this by 3D printing various moulds with ‘doubly sinusoidal’ topographies – i.e. two crossing sinusoidal waves in a pattern with various wavelengths and amplitudes (Figure 3). We are collaborating with Shoufeng Yang in the Engineering Sciences Unit to achieve this. We are then seeding cells onto polyacrylamide hydrogels made from these moulds, and we will investigate how the “steepness” of the topography affects the skin cells.
Figure 3: Polyacrylamide gel substrate made in 3D printed mould
In my final master year after summer I will participate in a group design project with six other students, which aims to design a bioreactor. The Vacation Bursary project will help me develop my understanding regarding mechanical forces and signals connected to cell growth and development, which will be very beneficial in my further studies within bioengineering.
MDR Vacation Bursary blog series available at: http://blog.soton.ac.uk/multidisciplinary/tag/vacation-bursary/
Categories: Blog. Tags: Bioengineering Sciences Group, Centre for Human Development, Dr Nick Evans, engineering and environment, epsrc, Pernille Fladsrud, stem cells, Stem Cells and Regeneration, and vacation bursary. Project names: Engineering mechanically-defined microenvironments for stem cells.