title: Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation.
abstract: Bioprinting as a promising but unexplored approach for cartilage tissue engineering has the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the targeted 3D locations with simultaneous polymerization. This study tested feasibility of using bioprinting for cartilage engineering and examined the influence of cell density, growth, and differentiation factors. Human articular chondrocytes were printed at various densities, stimulated transiently with growth factors and subsequently with chondrogenic factors. Samples were cultured for up to 4 weeks to evaluate cell proliferation and viability, mechanical properties, mass swelling ratio, water content, gene expression, ECM production, DNA content, and histology. Bioprinted samples treated with FGF-2/TGF-β1 had the best chondrogenic properties among all groups apparently due to synergistic stimulation of cell proliferation and chondrogenic phenotype. ECM production per chondrocyte in low cell density was much higher than that in high cell seeding density. This finding was also verified by mechanical testing and histology. In conclusion, cell seeding density that is feasible for bioprinting also appears optimal for human neocartilage formation when combined with appropriate growth and differentiation factors.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cui
authors.forename: Kurt
authors.initials: K
authors.lastname: Breitenkamp
authors.forename: Martin
authors.initials: M
authors.lastname: Lotz
authors.forename: Darryl
authors.initials: D
authors.lastname: D'Lima
mesh_terms: D000704:Analysis of Variance; D001709:Biotechnology / Q000379:methods*; D002356:Cartilage / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006651:Histocytochemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008689:Methacrylates / Q000737:chemistry; D055668:Photochemical Processes; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011509:Proteoglycans / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D008689:Methacrylates; D011509:Proteoglycans; D053773:Transforming Growth Factor beta1; C421283:poly(ethylene glycol)-dimethacrylate; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols