The rheology of hyaluronic acid is crucial to its performance in its many applications:
In dermal filler applications its rigidity, zero-shear viscosity, viscoelastic “relaxability” and viscosity under shear all contribute to its handling, injection, volumizing and residence time.
In ophthalmic viscosurgical gels the rheology determines whether the gel exhibits “dispersive” on “cohesive” characteristics, offering surface protection and film-forming or rigid structuring in use, and easy aspiration upon completion of a surgical procedure.
In viscosupplementation applications hyaluronic acid’s rheology imbues it with lubricating and film-forming qualities and its viscoelastic responses to the imposition of sudden or maintained stresses.
Hyaluronic acid, better known as Hyaluronan or HA, is a naturally occurring, high molecular-weight biopolymer, which has a wide range of uses such as medical procedures, pharmaceutical uses and cosmetic applications. Hyaluronic acid is created within the body and, combined with lubricin, forms a large part of skin and cartilage. Because of this, the rheological profile of Hyaluronic acid is crucial to the application of the HA.
Rheology of hyaluronic acid
As a polymer in solution, hyaluronic acid shows non-Newtonian and viscoelastic behaviour. Non-Newtonian liquids exhibit viscosity dependence upon the applied shear conditions, the most common type of non-Newtonian behaviour being shear-thinning, where viscosity decreases with increasing shear rate. This characteristic is beneficial as it allows for the product to be moved around and managed with greater ease, such as when pumped and filled in manufacturing processes, spread on the skin by a consumer or injected by a surgeon, but once at rest the product regains its viscosity, helping maintain its position.
While this characteristic is very desirable, it creates problems when attempting to measure the viscosity of hyaluronic acid solutions and gels. A single-point viscosity test such as that typically conducted on a simple viscometer is insufficient to fully characterize the material. Instead of this, a viscosity/shear rate profile (such as that shown in figure 1) is more suitable as a means of measuring this material.
Figure 1: Viscosity/shear rate profile of Hyaluronic acid solution
Shear thinning behaviour is clearly demonstrated within the results, with viscosity decreasing by a factor of over 20 times as the shear rate was increased. Interestingly, the sample demonstrated a Newtonian plateau at low shear rates. This plateau viscosity, known as a zero-shear viscosity, is a useful and important material attribute as this signifies the viscosity in an effectively at-rest condition. The magnitude of zero-shear viscosity and extent of the low-shear section of the curve are influenced by both molecular weight and weight distribution and hence can provide an indirect assessment of these factors for batch screening purposes.
Normal stress measurement and film-forming ability
From the shear rate profile a measurement of another useful property, normal stress generation under shear, can be obtained. Normal stress is a stress generated perpendicular to the direction of shear when an elastic fluid is sheared. The magnitude of normal stress generated often correlates well with the ability of a polymeric solution or gel to film-form. Film-forming ability is a pre-requisite for thick-film lubrication. On a research rheometer stress is measured using a force transducer fitted below the measuring plate. An example of the normal stress growth observbed with hyaluronic acid is shown below in figure 2:
Figure 2: Normal stress evolution with shear rate for HA solution