title: Silk fibroin matrices for the controlled release of nerve growth factor (NGF).
abstract: Nerve conduits (NC) for peripheral nerve repair should guide the sprouting axons and physically protect the axonal cone from any damage. The NC should also degrade after completion of its function to obviate the need of subsequent explanation and should optionally be suitable for controlled drug release of embedded growth factors to enhance nerve regeneration. Silk fibroin (SF) is a biocompatible and slowly biodegradable biomaterial with excellent mechanical properties that could meet the above stated requirements. SF material (films) supported the adherence and metabolic activity of PC12 cells, and, in combination with nerve growth factor (NGF), supported neurite outgrowth during PC12 cell differentiation. NGF-loaded SF-NC were prepared from aqueous solutions of NGF and SF (20%, w/w), which were air-dried or freeze-dried (freezing at -20 or -196 degrees C) in suitable molds. NGF release from the three differently prepared SF-NC was prolonged over at least 3 weeks, but the total amount released depended on the drying procedure of the NC. The potency of released NGF was retained within all formulations. Control experiments with differently dried NGF-lactose solutions did not evidence marked protein aggregation (SEC, HPLC), loss of ELISA-reactivity or PC12 cell bioactivity. This study encourages the further exploitation of SF-NC for growth factor delivery and evaluation in peripheral nerve repair.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Uebersax
authors.forename: Marta
authors.initials: M
authors.lastname: Mattotti
authors.forename: Michaël
authors.initials: M
authors.lastname: Papaloïzos
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001672:Biocompatible Materials / Q000737:chemistry*; D012831:Bombyx / Q000737:chemistry; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D024042:Collagen Type I / Q000737:chemistry; D003692:Delayed-Action Preparations; D004797:Enzyme-Linked Immunosorbent Assay; D005349:Fibroins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D007797:Laminin / Q000737:chemistry; D020932:Nerve Growth Factor / Q000032:analysis / Q000276:immunology / Q000493:pharmacokinetics*; D016501:Neurites / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D047011:Silk / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure; D017550:Spectroscopy, Fourier Transform Infrared; D013379:Substrate Specificity
chemical_list: D000085:Acetates; D001672:Biocompatible Materials; D002021:Buffers; D024042:Collagen Type I; D003692:Delayed-Action Preparations; D007797:Laminin; D047011:Silk; D005349:Fibroins; D020932:Nerve Growth Factor