Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins.

Abstract

Therapeutic proteins, the fastest growing class of pharmaceuticals, are subject to rapid proteolytic degradation in vivo, rendering them inactive. Sophisticated drug delivery systems that maintain protein stability, prolong therapeutic effects, and reduce administration frequency are urgently required. Herein, a mechanoresponsive hydrogel is developed contained within a soft robotic drug delivery (SRDD) device. In a step-change from previously reported systems, pneumatic actuation of this system releases the cationic therapeutic protein Vascular Endothelial Growth Factor (VEGF) in a bioactive form which is required for therapeutic angiogenesis, the growth of new blood vessels, in numerous clinical conditions. The ability of the SRDD device to release bioactive VEGF in a spatiotemporal manner from the hydrogel is tested in diabetic rats - a model in which angiogenesis is difficult to stimulate. Daily actuation of the SRDD device in the diabetic rat model significantly increased cluster of differentiation 31+ (CD31+) blood vessel number (p = 0.0335) and the diameter of alpha-smooth muscle actin+ (α-SMA+) blood vessels (p = 0.0025) compared to passive release of VEGF from non-actuated devices. The SRDD device combined with the mechanoresponsive hydrogel offers the potential to deliver an array of bioactive therapeutics in a spatiotemporal manner to mimic their natural release in vivo.