Collagen Type I and Aldehyde/Hydrazide-Modified Hyaluronic Acid Hydrogels for Tissue Engineering

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. While 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. Neither alone create an elastic network similar to tissues. While collagen type I networks have mechanical integrity, HA alone is a viscoelastic liquid and does not. Therefore, chemical modifications of HA are common to impart structural integrity. Designing and fully characterizing materials that incorporate collagen type I and chemically modified HA are essential.

In the current study, we investigated collagen type I and aldehyde/hydrazide-modified HA (HAX) for use as a tissue engineered construct. 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 (40 mg/mL or 4 mg/mL, respectively), these materials impose thick honeycomb structures or thin spider web-like structures respectively into the crosslinked network of ColHAX. Increasing HAX concentration in ColHAX gels increased the percentage of HA retained in the network from what was originally put in. When swollen, ColHAX gels increased in weight by 5-80%, increasing with increasing HAX:collagen ratio. Collagen alone decreased by 50% likely due to both collagen and water loss. Swollen ColHAX gels were stable for more than 4 weeks, whereas swollen HAX alone was stable for only 3 days before breaking apart. The elastic moduli of the ColHAX gels were greater than that of HAX alone. Results from this study suggest mechanical and physical properties from both collagen and HAX can be modulated to create ColHAX hybrid gels that are structurally stable, elastic, and have a high swelling capacity.