title: An ex vivo model using human osteoarthritic cartilage demonstrates the release of bioactive insulin-like growth factor-1 from a collagen-glycosaminoglycan scaffold.
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.
authors.affiliation: Orthopaedic Research Unit, University of Cambridge, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Wardale
authors.affiliation: IOP Publishing, Bristol, UK.
authors.forename: L
authors.initials: L
authors.lastname: Mullen
authors.affiliation: Orthopaedic Research Unit, University of Cambridge, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Howard
authors.affiliation: Tigenix, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ghose
authors.affiliation: Orthopaedic Research Unit, University of Cambridge, Cambridge, UK.
authors.forename: N
authors.initials: N
authors.lastname: Rushton
mesh_terms: D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007717:Knee / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D054457:Tissue Scaffolds
chemical_list: D016207:Cytokines; D058575:Decorin; D006025:Glycosaminoglycans; D007334:Insulin-Like Growth Factor I; D003094:Collagen
keywords: cartilage; osteoarthritis; regenerative medicine; scaffold