Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue.

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). 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-processing. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection. 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 methods. 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.

Dynamic mechanoelectrochemistry of polypyrrole membranes via shear-force tracking.

Mechanoelectrochemistry is the study of elastic and plastic deformation of materials during reversible reduction and oxidation processes. In this article, we introduce shear-force tracking as a method to dynamically measure mechanical (strain), chemical (ion transport), and electrical (applied redox potentials) responses of the conducting polymer polypyrrole (PPy) during redox reactions. This tracking technique uses a control algorithm to maintain a set distance between a ultramicroelectrode (UME) tip and a surface via shear-force regulation. Due to the sensitivity of shear-force signals in the near field of substrate surfaces, a significantly improved signal to noise ratio (20 : 1) is possible and allows for nanoscale measurement of redox events. Chemomechanical coupling (the ratio of ion transport to resultant extensional actuation) is calculated for PPy-based membranes of various thicknesses based on a mechanistic interpretation of charge storage in redox active conducting polymers. The measured dynamic response demonstrates that chemomechanical coupling is not a constant, as assumed in literature, but is dependent on the polymers state of charge and the direction (ingress/egress) of ion transport.

Mechanoelectrochemistry of PPy(DBS) from correlated characterization of electrochemical response and extensional strain.

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.