title: Poly(lactide-co-glycolide)/fibrin gel construct as a 3D model to evaluate gene therapy of cartilage in vivo.
abstract: Combination of gene therapy with tissue engineering can enhance the interplay between cells and matrix, leading to better restoration and regeneration of tissues and organs in vivo. In this study the PLGA/fibrin gel hybrids were employed to load lipofectamine/pDNA-TGF-β1 complexes and mesenchymal stem cells (MSCs) (experimental group), acting as a cartilage-mimetic tissue platform. The gene complexes distributed more evenly in the hybrid scaffolds, whereas they adhered onto the pore walls of the PLGA sponges. The filled fibrin gel rendered gene release in a slower manner, too. Moreover, the fibrin gel entrapped MSCs and contributed to a higher cell loading density in the hybrid constructs. In vivo assay showed that in the defects implanted with the experimental constructs both gene and protein expression levels of TGF-β1 were significantly higher than those of the fibrin-free group at weeks 1, 3, and 6 after surgery. The full articular cartilage defects repaired by the experimental group for 12 w were resurfaced by neo-tissues with a similar thickness, cell arrangement, and color to the normal neighboring cartilage and abundant glycosaminoglycans.
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: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.forename: Junzhou
authors.initials: J
authors.lastname: Yang
authors.forename: Chunfen
authors.initials: C
authors.lastname: Wang
authors.forename: Dongan
authors.initials: D
authors.lastname: Wang
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods; D006025:Glycosaminoglycans / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011098:Polyglactin 910 / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D012038:Regeneration / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D005782:Gels; D006025:Glycosaminoglycans; D053773:Transforming Growth Factor beta1; D011098:Polyglactin 910; D005337:Fibrin