Nanotechnology-based solutions for diabetic peripheral arterial disease
In vivo direct cell reprogramming has the potential to facilitate the development of safer and more effective patient-specific cell-based therapies. Current reprogramming methodologies, however, face major translational hurdles, including heavy reliance on viral transfection, and a highly stochastic nature, which often leads to inefficient and unsafe reprogramming outcomes. We developed and novel nanochanneled platform technology that overcomes these barriers by enabling deterministic transduction of reprogramming factors into tissues (with single-cell resolution) without the need for viral vectors. This nanotechnology-based approach promotes remarkably fast and efficient direct cellular reprogramming in vivo, as demonstrated with a newly-developed model of induced vasculature. Non-viral direct derivation of induced vasculature in vivo could find applications in the treatment of a number of disorders, including critical limb ischemia (CLI), which is a common affliction of diabetic patients. Nevertheless, currently no study has looked into developing virus-free methods for direct induction/reprograming of endothelial cells (in vitro or in vivo). Moreover, the regenerative potential of these cells has not been investigated within the context of diabetic CLI. Here we are proposing to develop an optimized method for direct nanochannel-based derivation of vascular tissue from support/stromal tissue, in vivo, and to study the extent to which this strategy induces functional recovery in a diabetic mouse model of CLI. Diabetic patients are susceptible to developing severe cases of peripheral arterial disease (PAD) that can result in CLI and significant downstream complications (e.g., ulcerations, gangrene, limb loss, etc.), which poses a substantial burden to the patient and the overall healthcare system.

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