Engineering and characterization of a hydrogel mimicking subcutaneous interstitial space

We have synthesized and characterized a collagen-hyaluronic acid hybrid network. The aim was to create a hydrogel mimicking the extracellular matrix of adipose tissue, primarily for use in in vitro studies of protein drug transport in the subcutaneous interstitial space. The network was created by covalently crosslinking methacryloyl-functionalized collagen type I and thiol-functionalized hyaluronic acid by means of thiol-Michael and thiol-ene photo-click reaction. The degree of modification corresponded to 74 % of the lysine and arginine groups on collagen, and 16 to 29 % of the carboxylate groups on hyaluronic acid, as determined with H-1 NMR. Circular dichroism measurements showed that the triple helix of modified collagen remained intact. Oscillatory shear rheology tests showed that the hydrated networks displayed viscoelastic properties characteristic of hydrogels. The storage modulus, measured at 1 Hz frequency in the linear viscoelastic range (<5%), varied in a controllable way between 1.5 and 4 kPa depending on the collagen concentration and collagen-to-hyaluronic acid ratio. The hydrogels had a lower collagen content (0.6--1.2 wt%) but similar hyaluronic acid content and shear modulus at low strain rates as the extracellular matrix in adipose tissue and were penetrable by albumin and lysozyme. The results show that the hydrogels are promising as model systems for investigations of drug transport.