Title: Enzymatic synthesis of hyaluronic acid vinyl esters for two-photon microfabrication of biocompatible and biodegradable hydrogel constructs
Language: English
Authors: Qin, Xiao-Hua 
Gruber, Peter 
Markovic, Marica 
Plochberger, Birgit 
Klotzsch, Enrico
Stampfl, Jürgen 
Ovsianikov, Aleksandr
Liska, Robert 
Category: Research Article
Forschungsartikel
Issue Date: 2014
Journal: Polymer Chemistry
ISSN: 1759-9962
Abstract: 
Two-photon polymerization (2PP) allows 3D microfabrication of biomaterial scaffolds with user-defined geometry. This technique is highly promising for 3D cell culture and tissue engineering. However, biological applications of 2PP require photopolymerizable hydrogels with high reactivity and low cytotoxicity. This paper describes a novel hydrogel system based on hyaluronic acid vinyl esters (HA-VE), which enabled fast 2PP-fabrication of 3D hydrogel constructs with μm-scale accuracy. A series of HA-VE macromers with tunable degrees of substitution were synthesized by lipasecatalyzed transesterification. HA-VE gels were proved to be injectable, photocurable, enzymatically degradable and mechanically comparable to various soft tissues. Owing to the unique molecular design, degradation products of HA-VE gels through hydrolysis are non-toxic polyvinyl alcohol and adipic acid. Furthermore, HA-VE gels were systematically characterized and compared to HA-acrylates (HA-AC) and HA-methacrylates (HA-MA) gels including macromer cytotoxicity, photoreactivity, swelling, and gel stiffness. Cytotoxicity assay with L929 fibroblasts revealed that HA-VE was significantly less toxic than HA-AC (P<0.01) and HA-MA (P<0.05). Crosslinking efficiency of HA-VE was comparable to HA-AC and much higher than HA-MA. Although the reactivity of HA-VE for homopolymerization was insufficient for 2PP, it was demonstrated that thiol-ene chemistry could substantially improve its reactivity. This optimization led to 2PP-fabrication of a HA-VE hydrogel construct with μm-scale accuracy. Low cytotoxicity, high reactivity and good biodegradability makes HA-VE promising candidates for biological applications in cell culture and tissue engineering.
DOI: 10.1039/c4py00792a
Library ID: AC11359638
URN: urn:nbn:at:at-ubtuw:3-1115
Organisation: E308 - Institut für Werkstoffwissenschaft und Werkstofftechnologie 
Publication Type: Article
Artikel
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