title: In vitro growth factor-induced bio engineering of mature articular cartilage.
abstract: Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Maturation involves gross morphological changes that occur through a process of synchronised growth and resorption of cartilage and generally ends at sexual maturity. The inability to induce maturation in biomaterial constructs designed for cartilage repair has been cited as a major cause for their failure in producing persistent cell-based repair of joint lesions. The combination of growth factors FGF2 and TGFβ1 induces accelerated articular cartilage maturation in vitro such that many molecular and morphological characteristics of tissue maturation are observable. We hypothesised that experimental growth factor-induced maturation of immature cartilage would result in a biophysical and biochemical composition consistent with a mature phenotype. Using native immature and mature cartilage as reference, we observed that growth factor-treated immature cartilages displayed increased nano-compressive stiffness, decreased surface adhesion, decreased water content, increased collagen content and smoother surfaces, correlating with a convergence to the mature cartilage phenotype. Furthermore, increased gene expression of surface structural protein collagen type I in growth factor-treated explants compared to reference cartilages demonstrates that they are still in the dynamic phase of the postnatal developmental transition. These data provide a basis for understanding the regulation of postnatal maturation of articular cartilage and the application of growth factor-induced maturation in vitro and in vivo in order to repair and regenerate cartilage defects.
authors.affiliation: Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales, UK. i.m.khan@swansea.ac.uk
authors.forename: Ilyas M
authors.initials: IM
authors.lastname: Khan
authors.forename: Lewis
authors.initials: L
authors.lastname: Francis
authors.forename: Peter S
authors.initials: PS
authors.lastname: Theobald
authors.forename: Stefano
authors.initials: S
authors.lastname: Perni
authors.forename: Robert D
authors.initials: RD
authors.lastname: Young
authors.forename: Polina
authors.initials: P
authors.lastname: Prokopovich
authors.forename: R Steven
authors.initials: RS
authors.lastname: Conlan
authors.forename: Charles W
authors.initials: CW
authors.lastname: Archer
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000254:growth & development*; D002417:Cattle; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008297:Male; D009924:Organ Culture Techniques / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology*
chemical_list: D053781:Transforming Growth Factor beta2; D016222:Fibroblast Growth Factor 2