(726b) Developing an Empirical Model for Designing Tunable Collagen and Hyaluronic Acid Blended Hydrogels

Collagen I and hyaluronic acid (HA) are commonly utilized to form hydrogels that mimic the extracellular matrix for tissue engineering applications. Scaffold microstructure, component incorporation, and modulus govern molecular transport and provide biochemical and mechanical signals for cellular proliferation, differentiation, and migration. Despite their widespread use in tissue engineering, the physical and mechanical properties of these materials are variable. In our study, we developed an empirical model toward the formation of tunable, well-defined, and robust collagen-HA blended hydrogels (ColHA) for a wide range of tissue engineering applications.

Statistical modeling was utilized to fully characterize the design space of the collagen and HA blended hydrogels. In particular, we probed the contribution of parameters, such as HA concentration, HA molecular weight, and the polymerization temperature of collagen, to modulating materials properties, including scaffold modulus, microstructure, and functional assays such as molecular transport through the gels. Hydrogels were formulated with 4 mg/mL of collagen, and physiologically relevant HA concentrations (0, 0.5, 1, and 2 mg/mL) and molecular weights (50, 500, and 1500 kDa) were chosen to fully represent various in vivo tissues and processes. A wide range of matrix polymerization temperatures (15, 26, and 37 °C) was investigated to capture the full range of fibril formation capabilities of collagen. Robust fabrication protocols were developed and validated by five people reproducing the matrix and resulted in uniform component incorporation and microstructure. ColHA gels polymerized at 26 °C resulted in gels with the highest complex modulus (G*), which was three times higher than those of gels polymerized at 37 °C. A Transwell assay was performed and highlighted the importance of electrostatic charge and viscous matrix effects for mass transport efficiency of various molecules traveling through the matrices. Overall, the results of this study demonstrate that ColHA gels span a large design space that can be tailored for tissue engineering applications with specific mechanical properties, fibril microstructure, equilibrium HA concentration, and macromolecule transport profiles.