title: Differential effects of growth factors on tissue-engineered cartilage.
abstract: The effects of four regulatory factors on tissue-engineered cartilage were examined with specific focus on the ability to increase construct growth rate and concentrations of glycosaminoglycans (GAG) and collagen, the major extracellular matrix (ECM) components. Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured in medium with or without supplemental insulin-like growth factor (IGF-I), interleukin-4 (IL-4), transforming growth factor-beta1 (TGF-beta1) or platelet-derived growth factor (PDGF). IGF-I, IL-4, and TGF-beta1 increased construct wet weights by 1.5-2.9-fold over 4 weeks of culture and increased amounts of cartilaginous ECM components. IGF-I (10-300 ng/mL) maintained wet weight fractions of GAG in constructs seeded at high cell density and increased by up to fivefold GAG fractions in constructs seeded at lower cell density. TGF-beta1 (30 ng/mL) increased wet weight fractions of total collagen by up to 1.4-fold while maintaining a high fraction of type II collagen (79 plus minus 11% of the total collagen). IL-4 (1-100 ng/mL) minimized the thickness of the GAG-depleted region at the construct surfaces. PDGF (1-100 ng/mL) decreased construct growth rate and ECM fractions. Different regulatory factors thus elicit significantly different chondrogenic responses and can be used to selectively control the growth rate and improve the composition of engineered cartilage.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Blunk
authors.forename: Alisha L
authors.initials: AL
authors.lastname: Sieminski
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Gooch
authors.forename: Donald L
authors.initials: DL
authors.lastname: Courter
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Hollander
authors.forename: A Menahem
authors.initials: AM
authors.lastname: Nahir
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Freed
mesh_terms: D000818:Animals; D002356:Cartilage / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects*; D002417:Cattle; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D023822:Tissue Engineering
chemical_list: D006133:Growth Substances