Available on-demand - S.SM06.04.05
A Tuneable Method of Nanostructuring Polymers as Surfaces for Tissue Growth
Thomas Chalklen1,Michael Smith1,Matthew Sims1,Sohini Kar-Narayan1
University of Cambridge1
Show Abstract
The biological world relies on a variety of stimuli: chemical, electrical and also mechanical. For the fields of regenerative medicine and tissue engineering, understanding these cues is an important pathway for directing tissue behaviour.
Currently however, our understanding of the effect of mechanical stimulation on cell behaviour is poor, but it is becoming clear that these cues play an important role in regulating phenotype, recently being used to direct stem cell differentiation, for example [1]. A major issue for this field remains that the stiffness of biological tissue is many orders of magnitude lower than that of bulk materials such as polymers or ceramics. Work is being done to address this stiffness imbalance, the majority through the use of hydrogels [2], but this approach has some drawbacks, as the stiffness of a hydrogel is directly correlated to its chemistry, so in order to change the stiffness we require a change in chemistry. In addition, hydrogels fail to provide routes to actively direct cell behaviour whilst in culture.
In this work we utilise template wetting to create a tuneable, low stiffness surface through the use of nanostructuring to alter the effective surface stiffness of a widely used piezoelectric bio-polymer, poly-l-lactic acid [3]. By altering the length of the resulting nanotubes, we have successfully shown a strong preference by induced Pluripotent Stem Cells (iPSCs) for higher aspect ratio, softer, surfaces, and furthermore demonstrated the long term viability of this surface for cell growth. It is concluded that this nanostructuring presents a viable, controllable route to providing appropriate mechanical stimuli. Moreover, by exploiting the piezoelectric properties of the polymer there is the opportunity for active mechanical stimulation in culture. The implementation of this mechanical control opens up new avenues for detection, characterisation and stimulation of cell mechanobiology, paving the way towards an externally addressable lab-on-a-chip device.
[1] Sun, M., Chi, G., Li, P., Lv, S., Xu, J., Xu, Z., … Li, Y. (2018). Effects of Matrix Stiffness on the Morphology, Adhesion, Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells. International Journal of Medical Sciences, 15(3), 257–268. https://doi.org/10.7150/ijms.21620
[2] Caliari, S. R., & Burdick, J. A. (2016). A practical guide to hydrogels for cell culture. Nature Methods, 13(5), 405–414. https://doi.org/10.1038/nmeth.3839
[3] Smith, M., Lindackers, C., McCarthy, K., & Kar-Narayan, S. (2019). Enhanced Molecular Alignment in Poly-l-Lactic Acid Nanotubes Induced via Melt-Press Template-Wetting. Macromolecular Materials and Engineering, 304(3), 1800607. https://doi.org/10.1002/mame.201800607