Rheology and Gelation of Hyaluronic Acid/Chitosan Coacervates

Abstract

Hyaluronic acid (HA) and chitosan (CHI) are biopolyelectrolytes which are interesting for both the medical and polymer physics communities due to their biocompatibility and semi-flexibility, respectively. In this work, we demonstrate by rheology experiments that the linear viscoelasticity of HA/CHI coacervates depends strongly on the molecular weight of the polymers. Moduli for coacervates were found significantly higher than those of individual HA and CHI physical gels. A remarkable 1.5-fold increase in moduli was noted when catechol-conjugated HA and CHI were used instead. This was attributed to the conversion of coacervates to chemical gels by oxidation of 3,4-dihydroxyphenylalanine (DOPA) groups in HA and CHI to di-DOPA crosslinks. These rheological results put HA/CHI coacervates in the category of strong candidates as injectable tissue scaffolds or medical adhesives.

Effect of Dynamically Arrested Domains on the Phase Behavior, Linear Viscoelasticity and Microstructure of Hyaluronic Acid – Chitosan Complex Coacervates

“…In other words, at pH 6, the dynamics of the HA–CHI coacervates are controlled not only by electrostatic interactions but also by relatively long-lived interactions with lifetimes longer than the ones probed by the rheological measurements performed here. A similar gel-like behavior for HA–CHI complex coacervates was recently observed by Kayitmazer et al at pH = 6.7 when formulated with CHI chains with a DDA of 37% and 76% . However, when formulated with CHI chains with an intermediate DDA of 54%, the HA–CHI complex coacervate remained a viscoelastic liquid.…”

“…A similar gel-like behavior for HA–CHI complex coacervates was recently observed by Kayitmazer et al at pH = 6.7 when formulated with CHI chains with a DDA of 37% and 76%. 34 However, when formulated with CHI chains with an intermediate DDA of 54%, the HA–CHI complex coacervate remained a viscoelastic liquid. The authors pointed out the intricate balance between blocky distribution of the hydrophobic acetyl units leading to the “freezing” of the complex coacervate dynamics and the decreased charge density along the CHI chains leading to shorter-lived electrostatic interactions.…”

“…Similar to pAA, chitosan (CHI) exhibits a strong water solubility dependence with pH until becoming fully insoluble at pH values above its p K a (around 6.5) . Hyaluronic acid (HA)–CHI complexes have been reported to have diverse applications in the biomedical field, including fibers, scaffolds and highly stretchable hydrogels. ,− To rationalize the design of these materials, in a recent study, Kayitmazer et al systematically investigated the effect of molecular weight and deacetylation degree of the CHI on the viscoelastic behavior of the resulting HA–CHI complex coacervates at pH and salt concentrations close to physiological conditions . However, the fundamentals related to the effect of CHI solubility as a function of the pH on the viscoelastic properties of the coacervate material still remain barely explored.…”

“… 9 , 29 − 33 To rationalize the design of these materials, in a recent study, Kayitmazer et al systematically investigated the effect of molecular weight and deacetylation degree of the CHI on the viscoelastic behavior of the resulting HA–CHI complex coacervates at pH and salt concentrations close to physiological conditions. 34 However, the fundamentals related to the effect of CHI solubility as a function of the pH on the viscoelastic properties of the coacervate material still remain barely explored. Understanding and controlling the interactions that play a role in the solubility of complex coacervates are of key importance for their processing and thus for the design of complex coacervate-based materials.…”

Understanding the Impacts of Molecular and Macromolecular Crowding Agents on Protein–Polymer Complex Coacervates

“…The resulting coacervate phase is enriched with interacting macromolecules and is in equilibrium with another liquid phase that is depleted in macromolecules. Complex coacervates can be prepared using a variety of macromolecules, including polysaccharides, − proteins, − nucleic acids, − and synthetic polymers. − Unique properties of complex coacervates, such as ultralow surface tension, high density, and tunable mechanical properties, − enable their use in a wide range of applications. Moreover, adjustment of the interactions between macromolecules can modify the properties of coacervates.…”