Mechano-activatable Microcapsules for Tunable Drug Delivery

Introduction A particularly desirable feature of controlled drug delivery is self-regulation, wherein physiological feedback actively regulates release kinetics. Extant systems in this domain commonly employ stimuli-responsive vehicles that rely on internal triggers to precipitate release, such as temperature, pH, or chemical reactions. 2 The sensitivity of these triggers can be tuned by biomaterial composition or structure to regulate release in a given physiologic or pathophysiologic state. However, to date, such delivery vehicles have not been specifically tuned for mechanically activated release. Tissues within the body experience mechanical perturbations across multiple force magnitudes and length scales, from mechanotransduction at the cell level to the dynamics of load-bearing joints. These forces not only maintain tissue homeostasis, but can also initiate degenerative processes when applied at supra-physiologic levels. 5 Given the centrality of mechanical loading in normal tissue function, our objective was to develop a mechanically activated drug delivery system to stimulate regeneration and repair in mechanically loaded musculoskeletal tissues (e.g. cartilage, muscle, bone). Towards this goal, we developed a novel class of mechano-activatable microcapsules (MAMCs, Ø~50-100μm), and illustrate here the tuning of design parameters to enable differential responses to varying applied mechanical stimuli.