Augmenting protein release from layer-by-layer functionalized agarose hydrogels

Recent work demonstrated the efficacy of combining layer-by-layer assembly with hydrogels to provide the controlled delivery of proteins for use in nerve repair scaffolds. In this work, we augmented the protein dose response by controlling and increasing the hydrogel internal surface area. Sucrose was added to agarose during gelation to homogenize the nanopore morphology, resulting in increased surface area per unit volume of hydrogel. The surface area of a range of compositions (1.5-5.0 wt% agarose and 0, 50 and 65 wt% sucrose) was measured. Gels were supercritically dried to preserve porosity enabling detailed pore morphology measurements using nitrogen adsorption and high resolution scanning electron microscopy. The resulting surface area, normalized by superficial gel volume, ranged between 6 m2/cm3gel and 56 m2/cm3gel. Using the layer-by-layer process to load lysozyme, a neurotrophic factor analog, a relationship was observed between surface area and cumulative dose response ranging from 176 to 2556 μg/mL, which is in the range of clinical relevance for the delivery of growth factors. In this work, we demonstrated that the ability to control porosity is key in tuning drug delivery dose response from layer-by-layer modified hydrogels.