title: Decoration of silk fibroin by click chemistry for biomedical application.
abstract: Silkfibroin (SF) has an excellent biocompatibility and its remarkable structure translates into exciting mechanical properties rendering this biomaterial particularly fascinating for biomedical application. To further boost the material's biological/preclinical impact, SF is decorated with biologics, typically by carbodiimide/N-hydroxysuccinimide coupling (EDC/NHS). For biomedical application, this chemistry challenges the product risk profile due to the formation of covalent aggregates, particularly when decoration is with biologics occurring naturally in humans as these aggregates may prime for autoimmunity. Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) provides the necessary specificity to avoid such intermolecular, covalent aggregates. We present a blueprint outlining the necessary chemistry rendering SF compatible with CuAAC and with a particular focus on structural consequences. For that, the number of SF carboxyl groups (carboxyl-SF; required for EDC/NHS chemistry) or azido groups (azido-SF; required for click chemistry) was tailored by means of diazonium coupling of the SF tyrosine residues. Structural impact on SF and decorated SF was characterized by Fourier transform infrared spectroscopy (FTIR). The click chemistry yielded a better controlled product as compared to the EDC/NHS chemistry with no formation of inter- and intramolecular crosslinks as demonstrated for SF decorated with fluorescent model compounds or a biologic, fibroblast growth factor 2 (FGF2), respectively. In conclusion, SF can readily be translated into a scaffold compatible with click chemistry yielding decorated products with a better risk profile for biomedical application.
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Hongshi
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Heusler
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Jones
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany; Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, PR China.
authors.forename: Linhao
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Werner
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Germershaus
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ritzer
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Tessa
authors.initials: T
authors.lastname: Luehmann
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany. Electronic address: l.meinel@pharmazie.uni-wuerzburg.de.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
mesh_terms: D001386:Azides / Q000737:chemistry; D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry; D003979:Diazonium Compounds / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005349:Fibroins / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001386:Azides; D003979:Diazonium Compounds; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D003300:Copper; D005349:Fibroins
keywords: Click chemistry; Decoration; Fibroblast growth factor 2; Silk fibroin