20th May
Invited Seminar at the <Glasgow Biomaterials Seminars>
Evelyn Yim, National University of Singapore, Institute of Mechanobiology
As each cell type and target cell type has different requirements off their surroundings her group developed a screening tool to establish the optimal cell type and application specific interface topology. The multiarchitecture chip has an area of a coverslip (22x22mm) and is covered with 10s of different topographies which are being copied into polymeric materials using high fidelity nanoimprint lithograhy.
Screening for effective ways to increase neuronal differentiation of neuronal progenitor cells (H1, H9) of the mouse it turned out that nanometric grooves were the best signal to provide. (Moe et al. Small 2012; Chua et al. Biomaterials 2014)
Interested in the underpinning cell biology, her group moved on to investigate the involvement of focal adhesions, which differ significantly in size and length, in the reaction of human mesenchymal stem cells to micro- or nanotopographies. Here the involvement of focal adhesion kinase (FAK) was firmly established using a combination of siRNA, inhibitors and knock in mice with super FAK. (Ankam et al. Acta Biomaterialia 2013; Teo et al. ACS Nano 2013).
As these signalling pathways are also active during development the thought arose if topographic signalling could not be used to influence embryonic stem cells. Here differentiation protocols are lengthy and could do with a boost in efficiency and effectiveness. Exploiting the understanding of neuronal differentiation gained earlier they introduced exposure to topography at various stages of the differentiation protocol. These protocols typically follow 3 stages 1st proliferation, then neurosphere formation (no adhesion to the substrate), and then differentiation when they are plated out. It turned out that exposing the cells during the 1st stage was already sufficient to introduce a bias towards neuronal differentiation, the underpinning regulation of e.g. histone and DNA modifications are being investigated. (Chan et al. Biomaterials 2013).
In the second part Evelyn focused on three applications of topographies and devices that her lab develops: corneal endothelium, small vascular grafts and directed endocytosis.
Corneal endothelium is a main regulating tissue for the state of the cornea, malfunction or damage can lead to blindness as a dysregulated cornea turns translucent. Here the optimal topography that the multiarchitecture chip threw out was pillars which were used to increase the proliferation of the isolated primary human cells. The nanopatterns increased differentiation probability and decreased batch to batch variation. (Muhammad et al. 2015)
Small vascular grafts created using crosslinked poly-vinyl-alcohol were successful in a rat model, but showed little internal coverage by endothelia. Here the aim is to increase coverage by internally patterning the substrate with nanopatterns. In a similar vein is the ongoing work to improve the endothelial coverage of stents. (Muhammad et al. Biomat Science 2014)
In the last part current work on developing means to direct and influence internalisation of materials by using topography to regulate endocytosis was discussed. (Teo et al. 2011 Biomaterials)
More about Evelyn Yim and her group at:
http://www.bioeng.nus.edu.sg/nanomed/index.html
Official page at NUS: http://www.bioeng.nus.edu.sg/people/PI/Evelyn/default.html