“Raspberry” Hierarchical Topographic Features Regulate Human Mesenchymal Stem Cell Adhesion and Differentiation via Enhanced Mechanosensing

An understanding of cellular mechanoresponses to well-defined synthetic topographic features is crucial for the fundamental research and biomedical applications of stem cells. Structured biointerfaces, in particular the ones with nanometer and/or micrometer surficial features, have drawn more attention in the past few decades. However, it is still difficult to integrate nanostructures and microstructures onto the synthesized biointerfaces to mimic the hierarchical architecture of the native extracellular matrix (ECM). Herein, a series of "raspberry"-like hierarchical surfaces with well-defined nanofeatures and tunable nano/microfeatures have been achieved via a catecholic polymer coating technique. Cellular responses to these hierarchical interfaces were systemically studied, indicating that the nanofeatures on the raspberry surfaces significantly enhanced the mechanosensing of human mesenchymal stem cells (hMSCs) to interfacial physical cues. Cell mechanotransduction was further investigated by analyzing focal adhesion assembling, cytoskeleton organization, cell nuclear mechanics, and transcriptional activity. The results suggest that nanosize surficial features could increase cellular mechanosensing to environment physical cues. The mechanotransduction and cell fate specification were greatly enhanced by the ECM mimicking nano/microhierarchical biointerfaces but the features should be in an optimized size.