Stem cells are the building blocks from which specialized cells are generated. In the body, the specialization of stem cells into a target cell type depends on the stem cell’s interactions with its environment. To emulate this complex process in the lab, specific biomolecules, termed differentiation factors, are delivered to stem cells to guide their development. Typically, these differentiation factors must be manually replenished during the entire differentiation period, which can last several weeks; this process is painstaking and hard to replicate across researchers. Now, writing in Science Advances, a collaboration led by Tae-Hyung Kim and Kyung Min Choi reports an autonomous platform that uses metal–organic framework (MOF) nanoparticles for the release of retinoic acid (RA), a differentiation factor that induces neurogenesis in stem cells to grow mature neurons. The platform leads to highly efficient stem cell differentiation with minimal external input.
However, nanoparticles can induce cytotoxicity in stem cells when in direct contact. To avoid this adverse effect, the researchers designed a platform (called SMENA, single MOF-embedded nanopit arrays) with nanoscale wells, or pits, to contain the MOF nanoparticles. The nanopit array is patterned through a technique called interference lithography. Control of the lithography conditions allows the fabrication of nanopits that are deep enough to prevent contact between the MOF nanoparticles and the stem cells, assuming that homogeneous insertion of the nanoparticles — that is, placing exactly one nanoparticle per nanopit — is achieved. Fulfilling this requirement necessitates the optimization of both nanoparticle size and array geometry, which is no trivial task. “After 2 years of optimization to capture single MOFs in each nanopit, the current SMENA was finally fabricated,” says Kim. “We found that MOF nanoparticles with diameters between 170 and 200 nm can be efficiently loaded onto the nanopit arrays at specific nanohole sizes and pitches.”
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