title: Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model.
abstract: Damaged cartilage has poor self-healing ability and usually progresses to scar or fibrocartilaginous tissue, and finally degenerates to osteoarthritis (OA). Here we demonstrated that one of alternative isoforms of IGF-1, mechano growth factor (MGF) acted synergistically with transforming growth factor β3 (TGF-β3) embedded in silk fibroin scaffolds to induce chemotactic homing and chondrogenic differentiation of mesenchymal stem cells (MSCs). Combination of MGF and TGF-β3 significantly increased cell recruitment up to 1.8 times and 2 times higher than TGF-β3 did in vitro and in vivo. Moreover, MGF increased Collagen II and aggrecan secretion of TGF-β3 induced hMSCs chondrogenesis, but decreased Collagen I in vitro. Silk fibroin (SF) scaffolds have been widely used for tissue engineering, and we showed that methanol treated pured SF scaffolds were porous, similar to compressive module of native cartilage, slow degradation rate and excellent drug released curves. At 7 days after subcutaneous implantation, TGF-β3 and MGF functionalized silk fibroin scaffolds (STM) recruited more CD29+/CD44+cells (P<0.05). Similarly, more cartilage-like extracellular matrix and less fibrillar collagen were detected in STM scaffolds than that in TGF-β3 modified scaffolds (ST) at 2 months after subcutaneous implantation. When implanted into articular joints in a rabbit osteochondral defect model, STM scaffolds showed the best integration into host tissues, similar architecture and collagen organization to native hyaline cartilage, as evidenced by immunostaining of aggrecan, collagen II and collagen I, as well as Safranin O and Masson's trichrome staining, and histological evalution based on the modified O'Driscoll histological scoring system (P<0.05), indicating that MGF and TGF-β3 might be a better candidate for cartilage regeneration. This study demonstrated that TGF-β3 and MGF functionalized silk fibroin scaffolds enhanced endogenous stem cell recruitment and facilitated in situ articular cartilage regeneration, thus providing a novel strategy for cartilage repair.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China; SARI Center for Stem Cell and Nanomedicine, Chinese Academy of Science, Shanghai 201210, PR China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: SARI Center for Stem Cell and Nanomedicine, Chinese Academy of Science, Shanghai 201210, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China.
authors.forename: Shuangchi
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: SARI Center for Stem Cell and Nanomedicine, Chinese Academy of Science, Shanghai 201210, PR China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China. Electronic address: yglv@cqu.edu.cn.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China. Electronic address: yanglibme@cqu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry*; D002454:Cell Differentiation; D019070:Cell Lineage; D003094:Collagen / Q000737:chemistry; D024043:Collagen Type II / Q000737:chemistry; D019245:Compressive Strength; D051445:Fibrocartilage / Q000737:chemistry; D005349:Fibroins / Q000737:chemistry; D005355:Fibrosis; D006801:Humans; D051457:Hyaline Cartilage / Q000737:chemistry*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D011817:Rabbits; D012038:Regeneration; D047011:Silk / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000166:cytology; D013314:Stress, Mechanical; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; D047011:Silk; D053782:Transforming Growth Factor beta3; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D005349:Fibroins
keywords: Articular cartilage regeneration; Fibrocartilage; Mechano growth factor (MGF); Silk fibroin; Stem cell recruitment