Tuneable cellulose nanocrystal and tropoelastin-laden hyaluronic acid hydrogels

Abstract

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.

The Fabrication of Gelatin–Elastin–Nanocellulose Composite Bioscaffold as a Potential Acellular Skin Substitute

“…The small dimensions of CNC also provided greater surface area and interstitial volume, which allowed the hydrogel to retain more water [ 51 ]. While other studies reported reduced swelling with increased CNC concentration [ 43 , 44 , 45 ], it should be emphasized that these studies used modified CNC. CNC oxidation with sodium periodate added a dialdehyde group to its structure, which reacts with the free amine group of gelatin through Schiff base formation [ 43 ].…”

“…CNC has no covalent interaction with gelatin unless it is functionalised with aldehyde groups via sodium periodate oxidation [ 43 , 44 ]. CNC could also be modified with diosgenin to allow it to be crosslinked with gelatin via genipin [ 45 ].…”

“…Increased elastin content has been shown to reduce the degradation rate of gelatin scaffolds as protein content increases [ 50 ]. Elastin also reduced the weight loss of alginate scaffolds, but the result was statistically insignificant [ 44 ]. In contrast, gelatin and elastin hydrogels degraded at a slightly faster rate than pure gelatin hydrogels, which is consistent with the present study [ 39 ].…”

“…The high hydroxyl content of CNC and the stability of its β-1, 4-glycosidic linkages against most enzymes provided better resistance for composite gelatin–cellulose nanofibre scaffolds [ 54 ]. Additionally, the functionalised CNC acting as cross-linkers increased the scaffold’s resilience against enzymatic biodegradation [ 44 ].…”

Naturally derived nano- and micro-drug delivery vehicles: halloysite, vaterite and nanocellulose

“…168 Silva et al prepared a composite hyaluronic acid/CNC/tropoelastin hydrogel as a cell growing substrate. 169 The incorporation of CNCs improved the hydrogel's stability against hydrolytic and enzymatic degradation due to the chemical bonding of CNCs and hyaluronic acid. The resulting gels were shown to support and promote cell adhesion, viability and growth, which is indispensable for tissue engineering and regeneration applications.…”