Scientists have found that engineering the topography on which stem cells differentiate could be as powerful an agent for change as their chemical environment.
Engineering the topography on which stem cells grow, and the mechanical forces working on them, could act as a powerful agent for change, a new study has revealed.
Stem cells respond to the stiffness, chemistry and topography of the environment. Thus, scientists are building an understanding of the complex signal controlling these responses in the hope of harnessing the knowledge and taking stem cell research further.
Other than increasing the potential to guide stem cells to create desired materials for research and clinical applications, using nano-scale topographies could eliminate (or, alternatively, enhance) steps, including feeder layers and synthetic induction supplements, currently used in stem cell culture.
In addition, the use of sophisticated prosthetics in future for regenerative medicine could feature surfaces with varied tissue zones for different purposes.
Laura McNamara of the University of Glasgow, UK, experts at the Centre for Cell Engineering, together with colleagues from Columbia University, New York, Nanotechnology Centre for Mechanics in Regenerative Medicine, and the Bone and Joint Research Group at the University of Southampton, UK, reviewed the latest developments in the use of nano-topography to direct stem cell differentiation.
They looked, in particular, at skeletal (mesenchymal) stem cells.
The researchers could maintain stem cells in the undifferentiated state, and determine the direction of their fate, by precise control of the surface features beneath them.
Stem cells have an uncanny ability to detect and respond to nano-scale grooves, pits and ridges, and are particularly sensitive to the spacing and regularity of these features.
Nano-topographical responsiveness has been observed in diverse cell types, including fibroblasts, osteoblasts, osteoclasts, endothelial, smooth muscle, epithelial, and epitenon cells.
"This was intriguing from the perspective of biomaterials, as it demonstrated that surface features of just a few nanometres could influence how cells will respond to, and formed tissue on, materials," said McNamara.
In particular, the authors envisaged applications involving engineered topography components for stem cells in regenerative medicine, for instance, in orthopaedics and dental implants.
A combination of different topographies could be used to differentially functionalise implants for distinct applications, or demarcate particular 'zones' within a single device.
For instance, orthopaedic implants designed with specific regions tailored to integrate with bone and improve the chances of implant fixation might join with other areas of the implant programmed to reduce excessive bony in growth.
Some surfaces with clinical potential included nano-structured titanium and diamond. A growing number of precision nano-fabrication techniques are becoming available to help carve out the substrates needed for this research.
Skeletal stem cells have even been shown to grow into non-skeletal cells (known as trans-differentiation) on surfaces with the right groves and ridges, and in some studies this has produced neural tissue.
"With the emergence of mechanical stimuli as critical modulators of cellular functionality, nano-topography should prove as an excellent tool for development of novel biomaterials, capable of promoting desirable cellular behaviour, discouraging unwanted cell responses, and preventing or ameliorating pathological changes," the authors wrote.
The study has been published in the Journal of Tissue Engineering.
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