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An ex vivo model using human osteoarthritic cartilage demonstrates the release of bioactive insulin-like growth factor-1 from a collagen-glycosaminoglycan scaffold.


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Authors

Wardale, J 
Mullen, L 
Howard, D 
Ghose, S 
Rushton, N 

Abstract

Biomimetic scaffolds hold great promise for therapeutic repair of cartilage, but although most scaffolds are tested with cells in vitro, there are very few ex vivo models (EVMs) where adult cartilage and scaffolds are co-cultured to optimize their interaction prior to in vivo studies. This study describes a simple, non-compressive method that is applicable to mammalian or human cartilage and provides a reasonable throughput of samples. Rings of full-depth articular cartilage slices were derived from human donors undergoing knee replacement for osteoarthritis and a 3 mm core of a collagen/glycosaminoglycan biomimetic scaffold (Tigenix, UK) inserted to create the EVM. Adult osteoarthritis chondrocytes were seeded into the scaffold and cultures maintained for up to 30 days. Ex vivo models were stable throughout experiments, and cells remained viable. Chondrocytes seeded into the EVM attached throughout the scaffold and in contact with the cartilage explants. Cell migration and deposition of extracellular matrix proteins in the scaffold was enhanced by growth factors particularly if the scaffold was preloaded with growth factors. This study demonstrates that the EVM represents a suitable model that has potential for testing a range of therapeutic parameters such as numbers/types of cell, growth factors or therapeutic drugs before progressing to costly pre-clinical trials.

Description

Keywords

cartilage, osteoarthritis, regenerative medicine, scaffold, Cartilage, Articular, Cell Movement, Chondrocytes, Collagen, Cytokines, Decorin, Extracellular Matrix, Glycosaminoglycans, Humans, In Vitro Techniques, Insulin-Like Growth Factor I, Knee, Osteoarthritis, Tissue Scaffolds

Journal Title

Cell Biochem Funct

Conference Name

Journal ISSN

0263-6484
1099-0844

Volume Title

33

Publisher

Wiley
Sponsorship
Engineering and Physical Sciences Research Council (DT/E005233/1)
The authors would like to kindly acknowledge funding from the EPSRC and Tigenix Ltd (LM), Technology Strategy Board and Tigenix Ltd (JW) and the NIHR (DH).