title: Synthesis of photo-crosslinkable hyaluronan with tailored degree of substitution suitable for production of water resistant nanofibers.
abstract: 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 200 g/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.
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic. Electronic address: huerta-angeles@contipro.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Brandejsová
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Knotková
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Hermannová
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Moravcová
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Šmejkalová
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02, Dolni Dobrouč, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
keywords: Chemical modification; Hyaluronic acid; Nanofibers; Photocross-linking