Synthesis of photo-crosslinkable hyaluronan with tailored degree of substitution suitable for production of water resistant nanofibers

• Published in: Carbohydrate polymers Vol. 137; pp. 255 - 263
• Main Authors: Huerta-Angeles, Gloria, Brandejsová, Martina, Knotková, Kateřina, Hermannová, Martina, Moravcová, Martina, Šmejkalová, Daniela, Velebný, Vladimír
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 10.02.2016
• Subjects: Chemical modification; Hyaluronic acid; Nanofibers; Photocross-linking; Chemical modification; Hyaluronic acid; Nanofibers; Photocross-linking
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.10.077

•Alfa, beta unsaturated grafted-hyaluronan suitable for cross-linking was prepared.•Degree of acrylation up to 35% was reached by a methodology using mixed anhydrides.•Highly reproducible reactions produce highly pure derivatives (up to 200g/batch).•Cross-linked nanofiber mats (scaffolds) formed a hydrogel with porous honeycomb structure. In this work, hyaluronan (HA) was grafted by a novel and an efficient mixed anhydrides methodology with (hetero)-aryl and aliphatic acrylic moieties suitable for cross-linking. A precise control of stoichiometry was achieved. Derivatives with degree of substitution (DS) below 20% did not show self-crosslinking. Due to mild reaction conditions, a negligible degradation of the polysaccharide was obtained. The influence of the feed components on the reaction efficiency and DS were studied up to 200g/batch. The structure of the modified HA was characterized by Infrared Spectroscopy, Nuclear Magnetic Resonance, SEC-MALS and chromatographic analyses. Enzymatic degradation of derivatives was performed and isolated dimers demonstrated to be non-cytotoxic. The feasibility of the grafted HA for electrospinning with subsequent photo-crosslinking to avoid nanofibers water dissolution was demonstrated. The biocompatibility of the material, its degradation products, and the formation of honeycomb porous structures also proved the potential of the material for future in vivo applications.