Modulation\nof Short-Term Delivery of Proteins from\nHydrogels

For modulation of\ncellular behavior, systems that can provide controlled\ndelivery of proteins (soluble signals) over a few hours to a few days\nare highly desirable. Conventional erosion-controlled systems are\ninadequate as their degradation spans days to months. Conversely,\nhydrogels offer quicker release but are limited by a high burst release\nthat can lead to cytotoxicity and rapid depletion of the permeant.\nTo avoid burst release and achieve controlled diffusion of proteins,\nwe propose exploiting electrostatic interactions between the hydrogel\nmatrix and proteins. Here we demonstrate this concept using two disparate\nhydrogel systems: (1) a chemically cross-linked protein (gelatin)\nmatrix and (2) a physically cross-linked polysaccharide (agarose)\nmatrix and three proteins having different isoelectric points. By\nintroducing fixed charges into the hydrogel matrix using carboxylated\nagarose (CA), the precise and controlled release of BSA, lactoferrin,\nand FGF2 over a few hours to days is demonstrated. Using electroendosmosis,\nwe further provide evidence for a clear role for CA in modulating\nthe release. Our findings suggest that the paradigm presented herein\nhas the potential to significantly enhance the design of hydrogel\nsystems for the delivery of proteins and RNA therapeutics for vaccines\nand biomedical applications ranging from tissue engineering to functional\ncoatings for medical devices.