title: Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by a spatially controlled gene delivery system in bilayered integrated scaffolds.
abstract: Engineering complex tissues is important but difficult to achieve in tissue regeneration. Osteochondral tissue engineering for the repair of osteochondral defect, involving simultaneous regeneration of bone and cartilage, has attracted considerable attention and also serves as an optimal model system for developing effective strategies aimed at regenerating complex tissues. In the present study, we formulated a bilayered gene-activated osteochondral scaffold consisting of plasmid TGF-β1-activated chitosan-gelatin scaffold for chondrogenic layer and plasmid BMP-2-activated hydroxyapatite/chitosan-gelatin scaffold for osteogenic layer. Mesenchymal stem cells seeded in each layer of the bilayered gene- activated osteochondral scaffold showed significant cell proliferation, high expression of TGF-β1 protein and BMP-2 protein respectively. The results showed that spatially controlled and localized gene delivery system in the bilayered integrated scaffolds could induce the mesenchymal stem cells in different layers to differentiate into chondrocytes and osteoblasts in vitro, respectively, and simultaneously support the articular cartilage and subchondral bone regeneration in the rabbit knee ostochondral defect model. This study gives the evidence that multi-tissue regeneration through the combination of biomimetic and multi-phasic scaffold design, spatially controlled and localized gene delivery system and multi-lineage differentiation of a single stem cell population represents a promising strategy for facilitating the development of complex tissue or organ systems.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.forename: Huajia
authors.initials: H
authors.lastname: Diao
authors.forename: Shiyu
authors.initials: S
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhao
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology*; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D018014:Gene Transfer Techniques; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D011817:Rabbits; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D053773:Transforming Growth Factor beta1