Stem cells and their microenvironment interact cooperatively to dictate their fates. Biomaterials are dynamically remodeled by stem cells, and stem cells sense and translate the changes into cell fate decisions. We have previously reported that adaptive biomaterials composed of fibronectin inserted into protein nanosheets at a liquid interface enhance neuronal differentiation of human mesenchymal stem cells (hMSCs). However, we could not decouple clearly the effect of ligand density from that of fibrillary structure on cellular function and fate. Here we present an adaptive biomaterial based on two-dimensional networks of protein nanofibrils at a liquid–liquid interface. Compared with flat protein nanosheets, this biomaterial enhances neuronal differentiation of hMSCs through a signaling mechanism involving focal adhesion kinase. Lipid raft microdomains in plasma membrane are found to play a central role in which hMSCs rapidly adapt to the dynamic microenvironment at the fluid interface. Our finding has substantial implications for regenerative medicine and tissue engineering.

Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials.

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