Tailoring Hydrogel Viscoelasticity with Physical and Chemical Crosslinking

Biological tissues are viscoelastic, demonstrating a mixture of fluid and solid responses to mechanical strain. Whilst viscoelasticity is critical for native tissue function, it is rarely used as a design criterion in biomaterials science or tissue engineering. We propose that viscoelasticity may be tailored to specific levels through manipulation of the hydrogel type, or more specifically the proportion of physical and chemical crosslinks present in a construct. This theory was assessed by comparing the mechanical properties of various hydrogel blends, comprising elastic, equilibrium, storage and loss moduli, as well as the loss tangent. These properties were also assessed in human articular cartilage explants. It was found that whilst very low in elastic modulus, the physical crosslinks found in gellan gum-only provided the closest approximation of loss tangent levels found in cartilage. Blends of physical and chemical crosslinks (gelatin methacrylamide (GelMA) combined with gellan gum) gave highest values for elastic response. However, a greater proportion of gellan gum to GelMA than investigated may be required to achieve native cartilage viscoelasticity in this case. Human articular chondrocytes encapsulated in hydrogels remained viable over one week of culture. Overall, it was shown that viscoelasticity may be tailored similarly to other mechanical properties and may prove a new criterion to be included in the design of biomaterial structures for tissue engineering.