Chondrogenesis of Human Mesenchymal Stem Cells by Local Transforming Growth Factor-Beta Delivery in a Biphasic Resorbable Carrier

• Published in: Tissue engineering. Part A 2010-02, Vol.16 (2), p.453-464
• Main Authors: Dickhut, Andrea, Dexheimer, Verena, Martin, Katja, Lauinger, Rebekka, Heisel, Christian, Richter, Wiltrud
• Format: Article
• Language: English
• Subjects: Biocompatible Materials - chemistry; Biomarkers - metabolism; Cartilage cells; Chondrogenesis - drug effects; Chondrogenesis - genetics; Collagen Type II - genetics; Collagen Type II - metabolism; DNA - metabolism; Drug Carriers - chemistry; Drug Delivery Systems; Fibrin Tissue Adhesive - pharmacology; Gene Expression Regulation - drug effects; Growth; Health aspects; Humans; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Original Articles; Proteoglycans - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem cells; Tissue engineering; Transforming Growth Factor beta1 - pharmacology; Transforming growth factors
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2009.0168

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-β1). Further, a possible advantage of partial autologous fibrin glue (PAF) over commercial FG was assessed. Collagen carriers seeded with 5 × 10 5 human MSCs with or without FG, PAF, or TGF-β1–upgraded FG were cultured for 6 weeks in chondrogenic medium with or without TGF-β1. 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-β1/construct mediated chondrogenesis as successfully as supply of TGF-β1 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-β1 which may be useful to enhance matrix-assisted repair strategies for damaged cartilage.