Directing Stem Cell Differentiation via Electrochemical Reversible Switching between Nanotubes and Nanotips of Polypyrrole Array

Abstract

Control of stem cell behaviors at solid biointerfaces is critical for stem-cell-based regeneration and generally achieved by engineering chemical composition, topography, and stiffness. However, the influence of dynamic stimuli at the nanoscale from solid biointerfaces on stem cell fate remains unclear. Herein, we show that electrochemical switching of a polypyrrole (Ppy) array between nanotubes and nanotips can alter surface adhesion, which can strongly influence mechanotransduction activation and guide differentiation of mesenchymal stem cells (MSCs). The Ppy array, prepared via template-free electrochemical polymerization, can be reversibly switched between highly adhesive hydrophobic nanotubes and poorly adhesive hydrophilic nanotips through an electrochemical oxidation/reduction process, resulting in dynamic attachment and detachment to MSCs at the nanoscale. Multicyclic attachment/detachment of the Ppy array to MSCs can activate intracellular mechanotransduction and osteogenic differentiation independent of surface stiffness and chemical induction. This smart surface, permitting transduction of nanoscaled dynamic physical inputs into biological outputs, provides an alternative to classical cell culture substrates for regulating stem cell fate commitment. This study represents a general strategy to explore nanoscaled interactions between stem cells and stimuli-responsive surfaces.

Materials Nanoarchitectonics as Cell Regulators

“…Wei, Deng and co-workers have nanoarchitected a dynamic platform for guiding mesenchymal stem cells differentiation on the basis of reversible electrochemical switching of a polypyrrole array between highly adhesive hydrophobic nanotubes and poorly adhesive hydrophilic nanotips ( Figure 6). [31] Changes of cell adhesive capability have significant influences on mechanotransduction activation to regulate mesenchymal stem cells differentiation. Multiple cycles between attachment and detachment of mesenchymal stem cells to the polypyrrole array induce activation of intracellular mechanotransduction and osteogenic differentiation.…”

New substrates for stem cell control

“…Fmoc-F 2 /S [42] pericyte chondrogenesis RADA-PRG (modified PuraMatrix w ) [43,44] mouse neonatal epidermal cells, rMSC neurogenesis RGD on decellularized pig heart valves [45] EPC proliferation Synthemax w [46] iPSC expansion and differentiation polymer enzymatically responsive PEG [47 -52] iPSC, hESC, mESC, MSC, organoids, mouse pancreatic progenitor gellan gum [53] hPSC 3D spheres methylcellulose [54] MSC chondrogenesis nanotopographically imprinted PCL [55,56] MSC maintenance and osteogenesis NO-releasing chitosan [57] hP-MSC angiogenic potential P(PEGMEMA-r-GMA-r-VDM) [58] MSC proliferation PEG with RGD and MMP tethering [59,60] MSC migration photodegradable PEG [61,62] MSC 'mechanical memory' polyacrylate/acrylamide thermoresponsive hydrogel [63 -65] hESC, MSC, mESC polyacrylate/polyurethane [66 -68] hESC, MSC, C6 rat GSC polypyrrole [69] MSC osteogenesis polystyrene TopoChip [70] iPSC proliferation polyurethane [71 -74] hESC-derived HE, HPC, iPSC-derived hepatocytes, H9 ternary polymer blends [75,76] STRO-1 þ skeletal SC, fetal skeletal SC rstb.royalsocietypublishing.org Phil. Trans.…”

Photocontrolled Multidirectional Differentiation of Mesenchymal Stem Cells on an Upconversion Substrate

“…Aso ne of the widely studied pluripotent stem cells, mesenchymal stem cells (MSCs) have been considered as the most eligible cells for skeletal tissue engineering and regenerative medicine. [1] Guiding the differentiation of stem cells into specific cell-types on the matrix efficiently is crucial for stem-cell-based regeneration. Tr aditionally,g rowth factors are often used to control stem-cell fate.H owever,t his approach is still facing disappointing clinical outcomes from trials.…”