Modifying Large Molecule Release from Hydrogels Using Microcapillary Channels Patterned with Microfibrous Templates

Tuning the bulk properties of hydrogels is essential to applying them as tools for regenerative medicine. Patterning microscale pores into hydrogels provides an avenue for modifying the mechanical and transport properties of the whole gel while preserving the properties of its polymeric network. Modern methods of fabricating such pores, however, struggle with producing continuous networks of pores without sacrificing large volumes of the solid hydrogel. Here we apply a thermoresponsive microfiber patterning technique to produce networks of microcapillaries (serving as anisotropic pores) throughout the full-thickness of interpenetrating hydrogels (IPgels), thereby modifying the release of large drug-analogues from the gel. Using FRAP, we demonstrated that the diffusion of IgG and 10kDa Dextran were significantly hindered by the reinforced polymer network of the IPgel. It was found that the presence of microcapillary channels in IPgels increased the total payload delivered by more than 10% over the first 2 days of release. Release curves were modeled by first-order release kinetics, the Ritger-Peppas Power Law and the Weibull model, and describe drug-release behaviors that were dominated by diffusion. Microcapillary gels showed a 40% decrease in half-max time as compared to solid gels according to first-order approximations, and a 20% increase in timescale factor according to Weibull modeling. It is our goal to demonstrate a scalable and broadly applicable method of fabricating microcapillary networks in drug excipients, enabling the development of robust, drug-laden hydrogels with tunable transport properties.