title: Synthesis and characterization of a self-fluorescent hyaluronic acid-based gel for dermal applications.
abstract: Combinations of polymer conjugates affording in situ gelation hold promise for treatment of pathological cavities (e.g., arthritis) and sustained drug release. In particular, hyaluronic acid (HA) functionalized with reactive groups is regarded as an excellent biomaterial due to its tunable cross-linking kinetics and mechanical properties. HA-based reagents, however, can be irritating to surrounding tissues due to the reactivity of pendant groups, and their fast gelation kinetics can result in poor cavity filling. In this study, a biocompatible "click" reaction between cyanobenzothiazole (CBT) and d-cysteine (d-Cys) is employed to produce HA-based conjugates for in situ gelation. Rheological studies conducted on a gel obtained from the combination of HA-CBT and HA-d-Cys indicate optimal gelation time and mechanical properties. Further, in vitro studies on porcine skin demonstrate the ability of the gel to form in situ upon subcutaneous injection or topical application, and to act as a reservoir for sustained release of protein therapeutics. Finally, the safety of the HA-based conjugates is demonstrated on human keratinocytes. The presented results demonstrate the applicability of the binary mixture for in situ gelation and the potential of the proposed system for a variety of biomedical applications.
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Menegatti
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Nino
authors.initials: N
authors.lastname: Ruocco
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zakrewsky
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sanchez De Oliveira
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Helgeson
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Leal
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA, 93106, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D011108:Polymers; D012212:Rheology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011108:Polymers; D006820:Hyaluronic Acid
keywords: click chemistry; hyaluronic acid; hydrogels; in situ gelation; subcutaneous injection; sustained drug release