Tuneable cellulose nanocrystal and tropoelastin-laden hyaluronic acid hydrogels

Hyaluronic acid (HA)-based hydrogels have been widely used as cell culture substrates, adhesives and fillers for clinical therapeutics, and drug delivery vehicles, with promising results. Due to the limited mechanical properties, degradation rates, and biological activity of HA, it is important that HA be chemically modified, cross-linked or reinforced with specific components to confer a versatile range of viscoelastic and biophysical cues. Herein, we present a toolbox comprising of a class of in situ cross-linkable hydrogels encompassing a blend of three components: HA, cellulose nanocrystals (CNCs) and tropoelastin (TROPO). The resulting hydrogels confer tenable mechanical and biological properties which benefit from the merits of the individual components. Incorporation of CNCs enhanced the hydrogel’s stability against hydrolytic and enzymatic degradation, due to the chemical integration of the nanoparticles within the HA mesh. Additionally, the incorporation of TROPO enhanced elasticity and resilience. Finally, the developed hydrogels demonstrated a positive in vitro biological response as they were able to support and promote the adhesion, viability and growth of the seeded fibroblasts. These results demonstrate a feasible approach for the production of hydrogels exhibiting key structural stability, biological response and improved elastic resilience that can be advantageously explored in acellular and cellular tissue engineering strategies for the regeneration of various tissues, such as the vocal fold.