Although cellular therapies represent a promising strategy for a number of conditions, current approaches face major translational hurdles, including limited cell sources and the need for cumbersome pre-processing steps (for example, isolation, induced pluripotency)1–6. In vivo cell reprogramming has the potential to enable more-effective cell-based therapies by using readily available cell sources (for example, fibroblasts) and circumventing the need for ex vivo pre-processing7,8. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection9,10. Moreover, capsid size constraints and/or the stochastic nature of status quo approaches (viral and non-viral) pose additional limitations, thus highlighting the need for safer and more deterministic in vivo reprogramming methods11,12. Here, we report a novel yet simple-to-implement non-viral approach to topically reprogram tissues through a nanochannelled device validated with well-established and newly developed reprogramming models of induced neurons and endothelium, respectively. We demonstrate the simplicity and utility of this approach by rescuing necrotizing tissues and whole limbs using two murine models of injury-induced ischaemia.

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This paper investigates nanostructured morphology-dependent charge storage and coupled mechanical strain of polypyrrole membranes doped with dodecylbenzenesulfonate (PPy(DBS)). Nanoscale features introduced in PPy(DBS) using phospholipid vesicles as soft-templates create a uniform and long-range order to the polymer morphology, and lead to higher specific capacitance. It is widely stated that nanostructured architecture offer reduced mechanical loading at higher charge capacities, but metrics and methods to precisely quantify coupled localized strains do not exist. Towards this goal, we demonstrate the use of scanning electrochemical microscope with shear force imaging hardware (SECM-SF) to precisely measure charge storage function and volumetric strain simultaneously, and define two metrics--filling efficiency and chemomechanical coupling coefficient to compare nanostructured morphologies and thicknesses. For thin membranes (smaller charge densities), planar and vesicle-templated membranes have comparable mechanoelectrochemical response. For thick membranes (0.4 to 0.8 C cm(-2)), a 15% increase in charge storage is associated with 50% reduction in extensional strain. These results allow for the formulation of rules to design nanostructured PPy(DBS)-based actuators and energy storage devices.