title: Fabrication of poly(lactide-co-glycolide) scaffold filled with fibrin gel, mesenchymal stem cells, and poly(ethylene oxide)-b-poly(L-lysine)/TGF-β1 plasmid DNA complexes for cartilage restoration in vivo.
abstract: A poly (lactide-co-glycolide) (PLGA) scaffold filled with fibrin gel, mesenchymal stem cells (MSCs) and poly(ethylene oxide)-b-poly (L-lysine) (PEO-b-PLL)/pDNA-TGF-β1 complexes was fabricated and applied in vivo for synchronized regeneration of cartilage and subchondral bone. The PEO-b-PLL/pDNA-TGF-β1 complexes could transfect MSCs in vitro to produce TGF-β1 in situ and up regulate the expression of chondrogenesis-related genes in the construct. The expression of heterogeneous TGF-β1 in vivo declined along with the prolongation of implantation time, and lasted for 3 and 6 weeks in the mRNA and protein levels, respectively. The constructs (Experimental group) of PLGA/fibrin gel/MSCs/(PEO-b-PLL/pDNA-TGF-β1 complexes) were implanted into the osteochondral defects of rabbits to restore the functional cartilages, with gene-absent constructs as the Control. After 12 weeks, the Experimental group regenerated the neo-cartilage and subchondral bone with abundant deposition of glycosaminoglycans (GAGs) and type II collagen. The regenerated tissues had good integration with the host tissues too. By contrast, the defects were only partially repaired by the Control constructs. qRT-PCR results demonstrated that expression of the chondrogenesis-marker genes in the Experimental group was significantly higher than that of the Control group, and was very close to that of the normal cartilage tissue.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering Zhejiang University, Hangzhou, 310027, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Junzhou
authors.initials: J
authors.lastname: Yang
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Tu
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
mesh_terms: D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D024043:Collagen Type II / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D005782:Gels; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011098:Polyglactin 910 / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology*; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; D005782:Gels; D053773:Transforming Growth Factor beta1; D011107:Polylysine; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D005337:Fibrin; D004247:DNA
keywords: PLGA scaffold; cartilage repair; fibrin gel; gene therapy; stem cell therapy