Stimulation Based Drug Release From Dual-Layered Microspheres

The ability to mimic biological release of growth factors during regeneration and repair has important applications in several tissue-engineered systems. PLGA microspheres hydrolyze in water, resulting in high burst release. Gelatin microspheres maintain controlled release but are susceptible to enzymatic degradation, resulting in nonlinear release. The goal of this project is to develop a bioengineered scaffold that allows sustained, linear growth-factor release that is fully controlled via electrical stimulation. We have fabricated a hyaluronic acid-carbon nanotube (HA-CNT) conductive nanofiber material that is seeded with our dual-layered PLGA-gelatin microspheres loaded with growth factors that can be controlled via electrical stimulation to maintain linear release. Electrical stimulation of the HA-CNT fibers allows for electrophoretic transport of positively charged proteins through the gelatin layer to initiate growth-factor release, and the PLGA allows continual linearized release. Growth factor release was tested in both fibroblasts and chick dorsal root ganglia model. Both cell types showed activity under electrically released growth factors.