title: PD98059-impregnated functional PLGA scaffold for direct tissue engineering promotes chondrogenesis and prevents hypertrophy from mesenchymal stem cells.
abstract: In cartilage tissue engineering from mesenchymal stem cells, it is important to suppress hypertrophy to produce a neocartilage with stable phenotypes of hyaline articular cartilage (AC). The aim of this study was to develop and test the usefulness of functional chondrogenic scaffolds that serve the purpose of hypertrophy suppression. PD98059-impregnated poly(lactic-co-glycolic acid) (PLGA) scaffold is fabricated and compared with transforming growth factor (TGF)-β2-immobilized scaffold. The PD98059 is continuously released from the scaffolds over 140 days in contrast to the rapid release in TGF-β2-immobilized scaffold. The in vitro culture results show that the PD98059-impregated scaffold is more effective in suppressing hypertrophy than the TGF-β2-immobilized scaffold while both scaffolds enhance chondrogenesis from human mesenchymal stem cells. After 10 weeks of in vivo implantation in rabbits, the osteochondral defects is successfully repaired in both PD98059-impregnated and TGF-β2-immobilized scaffold seeded with rabbit mesenchymal stem cells when evaluated grossly and microscopically. However, type X collagen is not observed from regenerated cartilage in PD98059-impregnated scaffold, whereas it is detected around chondrocytes in the TGF-β2-impregnated scaffolds. In addition, the PD98059-impregnated scaffold has better reconstitution of the subchondral plate. These results suggest that the use of the PD98059-impregnated scaffold leads to AC regeneration of better quality and prevents hypertrophy when implanted in the osteochondral defects.
authors.affiliation: 1 Department of Orthopaedics, Dongguk University Ilsan Hospital , Goyang, Republic of Korea.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jong Dae
authors.initials: JD
authors.lastname: Kim
authors.forename: Eun Jo
authors.initials: EJ
authors.lastname: Oh
authors.forename: Se Heang
authors.initials: SH
authors.lastname: Oh
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Gun-Il
authors.initials: GI
authors.lastname: Im
mesh_terms: D000328:Adult; D000818:Animals; D020219:Chondrogenesis / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006984:Hypertrophy / Q000517:prevention & control*; D055767:Immobilized Proteins / Q000494:pharmacology; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D055767:Immobilized Proteins; D053781:Transforming Growth Factor beta2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one