title: Mesenchymal cells condensation-inducible mesh scaffolds for cartilage tissue engineering.
abstract: Mesenchymal cells condensation is crucial in chondrogenic development. However current tissue-engineered scaffolds for chondrogenesis pay little attention to this phenomenon. In this study, we fabricate poly(l-lactide-co-glycolide) (PLGA)/poly(l-lactide) (PLLA) microfiber scaffolds and coat them with human fibroblast-derived matrix (hFDM) that is a decellularized extracellular matrix (ECM) obtained from in vitro cultured human lung fibroblasts (WI-38). Those scaffolds were then conjugated with heparin via EDC chemistry and subsequently immobilized with transforming growth factor (TGF)-β1. The amount of TGF-β1 was quantitatively measured and the release profile showed a continuous release of TGF-β1 for 4 weeks. Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) were seeded in four different scaffolds; control, fibronectin (FN)-coated, hFDM-coated, hFDM/TGF-β1 and subjected to chondrogenic differentiation in vitro for up to 28 days. Both hFDM and hFDM/TGF-β1 groups exhibited significantly more synthesis of glycosaminoglycan (GAG) and much better upregulation of chondrogenic markers expression. Interestingly, MSCs condensation that led to cell aggregates was clearly observed with time in the two hFDM-coated groups and the quantitative difference was obvious compared to the control and FN group. A mechanistic study in gene and protein level indicated that focal adhesion kinase (FAK) was involved at the early stage of cell adhesion and cell-cell contact-related markers, N-cadherin and neural cell adhesion molecule (NCAM), were highly up-regulated at later time point. In addition histological analysis proved that hFDM/TGF-β1 group was the most effective in forming neocartilage tissue in a rabbit articular cartilage defect model. Taken together, this study demonstrates not only the positive effect of hFDM on chondrogenesis of MSCs and cartilage repair but also provides an important insight toward the significance of in vitro mesenchymal condensation on chondrogenic development of MSCs.
authors: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors: In Gul
authors: IG
authors: Kim
authors: Dept of Technical Application, Korea Institute of Industrial Technology, Gyeonggi 426-910, Republic of Korea.
authors: Jaehoon
authors: J
authors: Ko
authors: Dept of Veterinary Medicine, KonKuk University, Seoul 143-701, Republic of Korea.
authors: Hye Rim
authors: HR
authors: Lee
authors: Dept of Veterinary Medicine, KonKuk University, Seoul 143-701, Republic of Korea.
authors: Sun Hee
authors: SH
authors: Do
authors: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept of Biomedical Engineering, Korea University of Science and Technology, Daejeon 305-350, Republic of Korea. Electronic address: kpark@kist.re.kr.
authors: Kwideok
authors: K
authors: Park
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002358:Cartilage, Articular / Q000254:growth & development*; D002454:Cell Differentiation; D049109:Cell Proliferation; D020219:Chondrogenesis / Q000502:physiology; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D020099:Coated Materials, Biocompatible; D006025:Glycosaminoglycans; D019006:Neural Cell Adhesion Molecules; D053773:Transforming Growth Factor beta1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Cartilage regeneration; Chondrogenesis; Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs); Mesenchymal condensation; Polymer mesh scaffold