Insight into hyaluronic acid molecular weight control

Abstract

Hyaluronic acid (HA) is a ubiquitous polysaccharide found in humans, animals, bacteria, algae and molluscs. Simple yet sophisticated, HA demonstrates unique and valuable rheological properties. In solution, HA behaves as a stiffened random coil and the resultant behaviour, even at low concentrations, is far from Newtonian or 'ideal'. These rheological properties are heavily influenced by molecular weight (MW), so it is not surprising that many of the biological functions of HA are dependent on molecular size. The current billion dollar market for HA continues to grow rapidly, both in gross production and the number of applications for its use. Increasing demand, in conjunction with a reticence to use animal-derived HA, has revitalised the market for HA produced by bacterial fermentation. Although the genes and pathways involved in bacterial production of HA are well characterised, the mechanisms that underlie HA MW control are less well understood. By performing a thorough analysis of the proposed mechanisms of MW control in bacterial fermentation, this mini-review tries to elucidate the challenges and future directions for bacterial HA biosynthesis.

Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

“…It is a crucial constituent of the extracellular matrix and contributes to the unique properties of connective tissue and cartilage. Therefore, hyaluronan and synthetically modified hyaluronan derivatives are of high interest for polymer chemistry, materials science, and regenerative medicine [1,2,3]. In particular, hydrogels from unmodified hyaluronan or thiolated hyaluronan (HA-SH) have been extensively studied [4,5,6].…”

Molar Mass Analysis of Hydrophobically Modified Hyaluronic Acid by SEC‐MALLS: Facing the Challenges of Amphiphilic Biomacromolecules

“…To illustrate the importance of the mobile phase in SEC method development, the HA samples were first analyzed using the generally accepted standard procedure, that is, an aqueous NaCl mobile phase, [19] where pure HA assumes a random coil conformation. [12,13] From the solubility studies, this solvent system completely dissolved samples with a DS of less than 2.5. For the sake of this study, samples with a higher DS, that is, HAM 01 and HAM 02 (see Table 1), were also dissolved and the soluble fractions analyzed.…”

“…In aqueous solution pure HA assumes a stiffened random coil conformation . Scott and coworkers proposed that in organic media (DMSO), the secondary structure involves interresidue hydrogen bonding between the amide hydrogen and the adjacent carboxylate group, while in aqueous solutions these are disrupted and replaced by polymer–solvent interactions.…”

“…In aqueous solution pure HA assumes a stiffened random coil conformation. [12][13][14] Scott and coworkers [15,16] proposed that in organic media (DMSO), the secondary structure involves interresidue hydrogen bonding between the amide hydrogen and the adjacent carboxylate group, while in aqueous solutions these are disrupted and replaced by polymer-solvent interactions. Although these studies were carried out on HA oligosaccharides, that is, di-, tetra-, hexa-, and octasaccharides (HA 2 , HA 4 , HA 6 , and HA 8 ), more recent studies have shown that this behavior in solution can be extended to high molar mass polymer structures (molar mass > 100 kg mol −1 ).…”

Synthetic biology strategies for improving microbial synthesis of “green” biopolymers

“…DO has a critical effect on molecular weight, possibly through affecting the abundance of precursors (74). The desired outcome of high titer leads to poor mixing and an increasingly anaerobic environment.…”