title: Insulin-like growth factor I releasing silk fibroin scaffolds induce chondrogenic differentiation of human mesenchymal stem cells.
abstract: Growth factor releasing scaffolds are an emerging alternative to autologous or allogenous implants, providing a biologically active template for tissue (re)-generation. The goal of this study is to evaluate the feasibility of controlled insulin-like growth factor I (IGF-I) releasing silk fibroin (SF) scaffolds in the context of cartilage repair. The impact of manufacturing parameters (pH, methanol treatment and drug load) was correlated with IGF-I release kinetics using ELISA and potency tests. Methanol treatment induced water insolubility of SF scaffolds, allowed the control of bioactive IGF-I delivery and did not affect IGF-I potency. The cumulative drug release correlated linearly with the IGF-I load. To evaluate the chondrogenic potential of the scaffolds, hMSC were seeded on unloaded and IGF-I loaded scaffolds in TGF-beta supplemented medium. Chondrogenic differentiation of hMSC was observed on IGF-I loaded scaffolds, starting after 2 weeks and more strongly after 3 weeks, whereas no chondrogenic responses were observed on unloaded control scaffolds. IGF-I loaded porous SF scaffolds have the potential to provide chondrogenic stimuli to hMSC. Evidence for in vivo cartilage (re)generation must be demonstrated by future, pre-clinical proof of concept studies.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland. lorenz.meinel@pharma.ethz.ch
authors.forename: Lorenz
authors.initials: L
authors.lastname: Uebersax
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D012831:Bombyx; D002356:Cartilage / Q000166:cytology / Q000254:growth & development / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D020219:Chondrogenesis / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D005349:Fibroins / Q000737:chemistry*; D005612:Freeze Drying; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D047011:Silk / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D006025:Glycosaminoglycans; D047011:Silk; C020341:glucosaminoglycans; D007334:Insulin-Like Growth Factor I; D004247:DNA; D005349:Fibroins