An array of tiny square pillars, ten times smaller than the width of a human hair, send out mechanical signals that can change the course of cellular development. A new technology using patterned microscale pillars implanted into the bone as part of a knee or hip replacement surgery, could speed up recovery after bone replacements by altering the shape, nuclear organization, and genetic activity of individual stem cells.
Scientists from Monash University, the Melbourne Centre for Nanofabrication, CSIRO, the Max Planck Institute for Medical Research and the Swiss Federal Institute of Technology in Lausanne, developed square micropillar arrays using UV nanoimprint lithography that essentially “trick” mesenchymal stem cells into becoming bone cells. Low-cost nanoimprint lithography allows for the creation of microscale patterns at high throughput and high resolution.
The researchers present demonstrate the capacity of the pillar arrays to reshape nuclear architecture through direct tension across the nuclear envelop and determines precise microstructural features that are able to influence mesenchymal stem cell fate. They show how the surface features of the array (substrate microtopography) regulate the organization of chromatin withing the nucleus, gene activity, and an osteogenic fate.
This new mechanism by which mechanical signals can be effectively harnessed using microtopographies for clinical applications such as bone implant technologies reduces reliance on biological factors such as growth hormones. The scientists show that four times as much bone could be produced using the new technology compared to current methods.
The findings were published in the Advanced Science article, “Precision Surface Microtopography Regulates Cell Fate via Changes to Actomyosin Contractility and Nuclear Architecture.”
“What this means is, with further testing, we can speed up the process of locking bone replacements with surrounding tissue, in addition to reducing the risks of infection,” says Jessica Frith, PhD, associate professor at Monash University’s Department of Materials Science and Engineering. “We’ve also been able to determine what form these pillar structures take and what size they need to be in order to facilitate the changes to each stem cell, and select one that works best for the application.”
“Harnessing surface microtopography instead of biological factor supplementation to direct cell fate has far-reaching ramifications for smart cell cultureware in stem cell technologies and cell therapy, as well as for the design of smart implant materials with enhanced osteo-inductive capacity,” says Victor Cadarso, PhD, senior lecturer at the Department of Mechanical and Aerospace Engineering at the Monash University.
The results confirm micropillars not only impacted the overall nuclear shape, but also changed the contents of the nucleus, says professor Nicolas Voelcker from the Monash Institute of Pharmaceutical Sciences, director of the Melbourne Centre for Nanofabrication and a senior author on the study. “The ability to control the degree of deformation of the nucleus by specifying the architecture of the underlying substrate may open new opportunities to regulate gene expression and subsequent cell fate.”
The team is now advancing this study into animal model testing.