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Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.


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Authors

Mullen, Leanne M 
Best, Serena M 
Ghose, Siddhartha 
Wardale, John 
Rushton, Neil 

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.

Description

Keywords

Cartilage, Cells, Cultured, Collagen Type II, Glycosaminoglycans, Humans, In Vitro Techniques, Insulin-Like Growth Factor I, Tissue Scaffolds

Journal Title

J Mater Sci Mater Med

Conference Name

Journal ISSN

0957-4530
1573-4838

Volume Title

26

Publisher

Springer Science and Business Media LLC
Sponsorship
Engineering and Physical Sciences Research Council (DT/F006977/1)
EPSRC and Tigenix UK Limited, Byron House, Cambridge Business Park, Milton Road, Cambridge, are gratefully acknowledged for a studentship for L.M.M.