3d stem cell niche engineering via two-photon laser polymerization

A strategy to modulate the behavior of stem cells in culture is to mimic structural aspects of the native cell–extracellular matrix (ECM) interaction. An important example of such artificial microenvironments for stem cell culture is the so-called “synthetic niche.” Synthetic niches can be defined as polymeric culture systems mimicking at least one aspect of the interactions between stem cells and the extracellular surroundings, including biochemical factors (e.g., the delivery of soluble factors) and/or biophysical factors (e.g., the microarchitecture of the ECM). Most of the currently available approaches for scaffold fabrication, based on self-assembly methods, do not allow for a submicrometer control of the geometrical structure of the substrate, which might play a crucial role in stem cell fate determination. A novel technology that overcomes these limitations is laser two-photon polymerization (2PP). Femtosecond laser 2PP is a mask-less direct laser writing technique that allows manufacturing three dimensional arbitrary microarchitectures using photosensitive materials. Here, we report on the development of an innovative culture substrate, called the “nichoid,” microfabricated in a hybrid organic–inorganic photoresist called SZ2080, to study mesenchymal stem cell mechanobiology.