(89b) In Vitro Tissue Model with Collagen and Aldehyde/Hydrazide-Modified Hyaluronic Acid Hydrogels

Collagen and hyaluronic acid (HA) are major components of the extracellular matrix of many native tissues. Hydrogels composed of collagen and HA are capable of mimicking various natural tissue material properties. Although the use of collagen and HA are common in the tissue engineering community, the physical and mechanical properties of these materials are variable and poorly understood. Therefore, chemical modifications of HA are common to impart structural integrity. Designing and fully characterizing materials that incorporate collagen I and chemically modified HA are essential.

In the current study, we investigated collagen I and aldehyde/hydrazide-modified HA (HAX) for use as a tissue model by delineating design rules for ColHAX gels and determining the range of properties that can be achieved when you vary either the collagen or HA concentration. Hydrogel formulations with collagen at 2, 4, and 6 mg/mL and HAX at 20, 30, and 40 mg/mL were combined to form hybrid ColHAX gels. When either HAX or collagen are at sufficiently high concentrations, these materials impose thick honeycomb structures or thin spider web-like structures, respectively, into the crosslinked network of ColHAX. The addition of HAX to collagen decreases the pore size and collagen fibril length. Increasing the HAX concentration in ColHAX gels increased the percentage of HA retained in the network. There was no detectable loss of collagen from the ColHAX gel networks. When swollen, ColHAX gels varied in percent weight change from a decrease of 11% to an increase of 65% as the HAX:collagen ratio increased. Collagen gels alone decreased in weight by 59% due to water loss. Swollen ColHAX gels were stable for more than 4 weeks, whereas swollen HAX alone was stable for only 1 day before breaking apart. When proteins of varying characteristics were added to ColHAX gels, the percent released from each gel was dependent on charge and size of the protein and charge and pore size of the matrix. Results from this study demonstrate that ColHAX hybrid gels are structurally stable, soft, and have a high swelling capacity. These ColHAX gels span a large range of material properties and attain different protein release profiles for the tunability of different tissue types. Overall, this study delineates design rules for formulating ColHAX hydrogels that are tailored for applications requiring specific mechanical and physical properties.