title: Precise tailoring of tyramine-based hyaluronan hydrogel properties using DMTMM conjugation.
abstract: Injectable tyramine modified hyaluronic acid (HA-Tyr) hydrogels which are bio-orthogonally cross-linked with horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) are excellent candidate biomaterials for drug delivery, regenerative medicine and tissue engineering. Ligation of tyramine to HA has been reported using the very well established N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) chemistry. Here we demonstrate the applicability of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as an alternative coupling agent to synthesize HA-Tyr conjugates. The optimized derivatization process allows accurate control of the degree of substituted Tyr on hyaluronan (DSmol). Hence, viscoelastic properties, in vitro swelling and enzymatic digestion profiles of the crosslinked hydrogels can be precisely tuned via DSmol. Our study demonstrates the advantages of DMTMM conjugation as a powerful tool to synthesize HA-Tyr hydrogels with properties exactly tailored for biomedical applications.
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland; ETH Zurich, Cartilage Engineering+Regeneration, Department of Health, Science and Technology, Zürich, Switzerland. Electronic address: claudia.loebel@aofoundation.org.
authors.forename: Claudia
authors.initials: C
authors.lastname: Loebel
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Este
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: ETH Zurich, Cartilage Engineering+Regeneration, Department of Health, Science and Technology, Zürich, Switzerland.
authors.forename: Marcy
authors.initials: M
authors.lastname: Zenobi-Wong
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Eglin
mesh_terms: D004355:Drug Stability; D004548:Elasticity; D006820:Hyaluronic Acid / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007700:Kinetics; D009025:Morpholines / Q000737:chemistry*; D012212:Rheology; D013696:Temperature; D014439:Tyramine / Q000737:chemistry*; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: C467606:4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; D009025:Morpholines; D014867:Water; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D014439:Tyramine
keywords: 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) (PubChem CID: 2734059); Hyaluronic acid; Hyaluronic acid sodium salt (PubChem CID: 23663392); Hydrogel; N-(3-dimethylaminopropyl)-N′′-ethylcarbodiimide hydrochloride (EDC) (PubChem CID: 2723939); N-hydroxysuccinimide (NHS) (PubChem CID: 80170); Tyramine; Tyramine hydrochloride (PubChem CID: 66449)