Protein-mediated gelation and nano-scale assembly of unfunctionalized hyaluronic acid and chondroitin sulfate [version 2; peer review: 2 approved, 1 approved with reservations]

• Published in: F1000 research Vol. 7; p. 1827
• Main Authors: Tabet, Anthony, Park, June Y, Shilts, Jarrod, Sokolowski, Kamil, Rana, Vijay K, Kamp, Marlous, Warner, Nina, Hoogland, Dominique, Scherman, Oren A
• Format: Journal Article
• Language: English
• Published: London Faculty of 1000 Ltd 2019; F1000 Research Ltd
• Subjects: Acids; Albumin; Central nervous system; Chondroitin sulfate; Crystal structure; Datasets; Electrostatic properties; Extracellular matrix; Gelation; Glycosaminoglycans; Hyaluronic acid; Hydrogels; Light scattering; Mechanical properties; Molecular weight; Nanoparticles; Physiology; Polymers; Polysaccharides; Proteins; Rheology; Scanning electron microscopy; Self-assembly; Spectroscopy; Tissue engineering; Transmission electron microscopy; United Kingdom > UK; chondroitin sulfate; protein-polymer assembly; hyaluronic acid
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.16929.2

Background: Hyaluronic acid (HA) is a major component of the extracellular matrix (ECM) in the central nervous system and the only purely supramolecular glycosaminoglycan. Much focus has been given to using this high molecular weight polysaccharide for tissue engineering applications. In most studies, HA is covalently functionalized with moieties that can facilitate network formation through physical self-assembly, or covalent crosslinking (e.g. photo-catalyzed) as the polysaccharide does not gel on its own. However, these crosslinks are not the driving force of HA self-assembly in biological tissues.
Methods: Oscillatory rheology, dynamic light scattering, and scanning electron microscopy were used to study albumin/HA structures. Dynamic light scattering and transmission electron microscopy were used to study albumin/chondroitin sulfate (CS) structures. UV-vis spectroscopy was used to demonstrate the potential for using protein-crosslinked polymers as an ECM-mimetic model to study transport of hydrophilic small molecules.
Results: We examine the intermolecular interactions of two major glycosaminoglycans found in the human brain, HA and the lower molecular weight CS, with the model protein albumin. We report the properties of the resulting micro- and nano-materials. Albumin/HA mixtures formed supramolecular gels, and albumin/CS mixtures formed micro- and nanoparticles. These systems are formed from unfunctionalized polysaccharides, which is an attractive and simpler method of forming HA hydrogels and CS nanoparticles than functional chemistry-based approaches such as chemically modifying the polymer backbones. We also summarize the concentrations of HA and CS found in various mammalian brains, which could potentially be useful for biomimetic scaffold development in tissue engineering.
Conclusions: Simple preparation and combination of commercially available charged biomacromolecules rapidly result in interesting self-assembled materials with structures at the micron and nanometer length-scales. Such materials may have utility in serving as cost-effective and simple models of nervous system electrostatic interactions and as
in vitro drug release and model system for ECM transport studies.