title: New scaffolds encapsulating TGF-β3/BMP-7 combinations driving strong chondrogenic differentiation.
abstract: The regeneration of articular cartilage remains an unresolved question despite the current access to a variety of tissue scaffolds activated with growth factors relevant to this application. Further advances might result from combining more than one of these factors; here, we propose a scaffold composition optimized for the dual delivery of BMP-7 and TGF-β3, two proteins with described chondrogenic activity. First, we tested in a mesenchymal stem cell micromass culture with TGF-β3 whether the exposure to microspheres loaded with BMP-7 would improve cartilage formation. Histology and qRT-PCR data confirmed that the sustained release of BMP-7 cooperates with TGF-β3 towards chondrogenic differentiation. Then, we optimized a scaffold prototype for tissue culture and dual encapsulation of BMP-7 and TGF-β3. The scaffolds were prepared from poly(lactic-co-glycolic acid), and BMP-7/TGF-β3 were loaded as nanocomplexes with heparin and Tetronic 1107. The scaffolds showed the sustained release of both proteins over four weeks, with minimal burst effect. We finally cultured human mesenchymal stem cells on these scaffolds, in the absence of exogenous chondrogenic factor supplementation. The cells cultured on the scaffolds loaded with BMP-7 and TGF-β3 showed clear signs of cartilage formation macroscopically and histologically. RT-PCR studies confirmed a clear upregulation of cartilage markers SOX9 and Aggrecan. In summary, scaffolds encapsulating BMP-7 and TGF-β3 can efficiently deliver a cooperative growth factor combination that drives efficient cartilage formation in human mesenchymal stem cell cultures. These results open attractive perspectives towards in vivo translation of this technology in cartilage regeneration experiments.
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Avda. Barcelona s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Crecente-Campo
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Avda. Barcelona s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Erea
authors.initials: E
authors.lastname: Borrajo
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Avda. Barcelona s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Avda. Barcelona s/n, 15782 Santiago de Compostela, Spain. Electronic address: marcos.garcia@usc.es.
authors.forename: Marcos
authors.initials: M
authors.lastname: Garcia-Fuentes
mesh_terms: D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects*; D004338:Drug Combinations; D004339:Drug Compounding; D006801:Humans; D019344:Lactic Acid; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012038:Regeneration / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D055419:Bone Morphogenetic Protein 7; D004338:Drug Combinations; D053782:Transforming Growth Factor beta3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Cartilage; Controlled release; Growth factors; PLGA; Scaffolds; Tissue engineering