title: Chondrogenesis of human mesenchymal stem cells by local transforming growth factor-beta delivery in a biphasic resorbable carrier.
abstract: Little is known about the potential of growth factor-augmented biphasic implants composed of a gel and a solid scaffold to enhance chondrogenesis of mesenchymal stem cells (MSCs). We analyzed whether a collagen type I/III carrier and fibrin glue (FG) combined to a biphasic construct support in vitro chondrogenesis of MSCs and allow for local release of bioactive transforming growth factor-beta1 (TGF-beta1). Further, a possible advantage of partial autologous fibrin glue (PAF) over commercial FG was assessed. Collagen carriers seeded with 5 x 10(5) human MSCs with or without FG, PAF, or TGF-beta1-upgraded FG were cultured for 6 weeks in chondrogenic medium with or without TGF-beta1. Pellets with or without FG/PAF served as controls. FG and collagen carriers allowed strong upregulation of COL2A1, AGC, and COL10A1 mRNA, deposition of collagen-type II, and mediated a significantly higher proteoglycan content compared with biomaterial-free pellets. Collagen-carrier groups contained significantly more proteoglycan than FG and PAF pellets, whereas biphasic PAF-carrier constructs were inferior to FG-carrier constructs. Upgrading of biphasic FG-carrier constructs with 50 ng TGF-beta1/construct mediated chondrogenesis as successfully as supply of TGF-beta1 via the medium. In conclusion, the biphasic carrier constructs showed a high biofunctionality by continuous form stability with improved chondrogenesis and long-term local supply of bioactive TGF-beta1 which may be useful to enhance matrix-assisted repair strategies for damaged cartilage.
authors.affiliation: Division of Experimental Orthopaedics, Orthopaedic University Hospital, Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dickhut
authors.forename: Verena
authors.initials: V
authors.lastname: Dexheimer
authors.forename: Katja
authors.initials: K
authors.lastname: Martin
authors.forename: Rebekka
authors.initials: R
authors.lastname: Lauinger
authors.forename: Christian
authors.initials: C
authors.lastname: Heisel
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Richter
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D015415:Biomarkers / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D024043:Collagen Type II; D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D011509:Proteoglycans; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D004247:DNA