title: Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.
abstract: Tissue engineering is a promising technique for cartilage repair. Toward this goal, a porous collagen-glycosaminoglycan (CG) scaffold was loaded with different concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth factor delivery device. The biological response was assessed by monitoring the amount of type II collagen and proteoglycan synthesised by the chondrocytes seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1 released into the media was highest at day 4. This initial IGF-1 release could be modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1. Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating ECM deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo.
authors.affiliation: Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2 3QZ, UK, mcm.leanne@gmail.com.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Mullen
authors.forename: Serena M
authors.initials: SM
authors.lastname: Best
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Ghose
authors.forename: John
authors.initials: J
authors.lastname: Wardale
authors.forename: Neil
authors.initials: N
authors.lastname: Rushton
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Cameron
mesh_terms: D002356:Cartilage / Q000254:growth & development / Q000502:physiology*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D054457:Tissue Scaffolds
chemical_list: D024043:Collagen Type II; D006025:Glycosaminoglycans; D007334:Insulin-Like Growth Factor I