Swelling of Collagen-Hyaluronic Acid Tissue-Equivalents: An Experimental Model to Evaluate Residual Stress in Soft Tissues

Collagen gel tissue-equivalents (TEs), which are simple model tissues with tunable properties, have been used to explore many properties of soft tissues, such as how structural and compositional properties affect mechanical function [1–4]. One aspect not captured in previous TE formulations is residual stress due to interactions among components, which has an important functional role in many tissues (e.g., blood vessels [5], ligaments [6], annulus fibrosus [7]). Since the in vivo stress state of native tissues is not easily replicated in TE fabrication, a different method for “pre-stressing” collagen networks of TEs was necessary. To this end, co-gel TEs were fabricated by adding hyaluronic acid (HA) to reconstituted Type-I collagen (Col) gels. When placed in solutions of varying osmolarity, HA-Col TEs swell as the HA binds water, which in turn will stretch (and stress) the collagen network. In this way, TEs with residual stress (i.e., pre-stressed collagen fibers) can be fabricated and evaluated in order to elucidate relationships between residual stress and functional properties. Therefore, the goals of the present study were to fabricate HA-Col TEs, make initial measurements of their swelling properties, and quantify the mechanical response and changes in microstructural organization under applied tensile load.