title: High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF.
abstract: Interference screw in the fixation of autologous tendon graft to the bone tunnel is widely accepted for the reconstruction of anterior cruciate ligament (ACL), but the regeneration of fibrocartilaginous entheses could hardly be achieved with the traditional interference screw. In the present work, biodegradable high-purity magnesium (HP Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1 and SOX-9), and glycosaminoglycan (GAG) production in vitro. The HP Mg screw was applied to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium (Ti) screw as the control. The femur-tendon graft-tibia complex was retrieved at 3, 6, 9 and 12 weeks. Gross observation and range of motion (ROM) of the animal model reached normal levels at 12 weeks. No sign of host reaction was found in the X-ray scanning. The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL, and the ultimate load to failure and stiffness increased 12 weeks after surgery. In the histological analysis, the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery, whereas a disorganized fibrocartilage layer was found in the Ti group. In the immunohistochemical analysis, highly positive staining of BMP-2, VEGF and the specific receptor for BMP-2 (BMPR1A) was shown at the tendon-bone interface of the HP Mg group compared with the Ti group. Furthermore, the HP Mg group had significantly higher expression of BMP-2 and VEGF than the Ti group in the early phase of tendon-bone healing, followed by enhanced expression of fibrocartilage markers and GAG production. Therefore we proposed that the stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis of Mg materials. HP Mg was promising as a biodegradable interference screw with the potential to promote fibrocartilaginous entheses regeneration in ACL reconstruction.
authors.affiliation: Orthopaedic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Orthopaedic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Han
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: zcl@sjtu.edu.cn.
authors.forename: Changli
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; Suzhou Origin Medical Technology Co. Ltd., Suzhou 215513, China.
authors.forename: Shaoxiang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Hongliu
authors.initials: H
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Ni
authors.affiliation: Orthopaedic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.affiliation: Suzhou Origin Medical Technology Co. Ltd., Suzhou 215513, China.
authors.forename: Yuanzhuang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Suzhou Origin Medical Technology Co. Ltd., Suzhou 215513, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Suzhou Origin Medical Technology Co. Ltd., Suzhou 215513, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Orthopaedic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; Suzhou Origin Medical Technology Co. Ltd., Suzhou 215513, China. Electronic address: xnzhang@originmedtech.com.
authors.forename: Xiaonong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Orthopaedic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: chaiyimin@vip.163.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Chai
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods*; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D001863:Bone Screws; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D004195:Disease Models, Animal; D051445:Fibrocartilage / Q000000981:diagnostic imaging / Q000473:pathology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D011817:Rabbits; D016059:Range of Motion, Articular / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D013710:Tendons / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D006025:Glycosaminoglycans; D042461:Vascular Endothelial Growth Factor A; D052005:Bone Morphogenetic Protein Receptors, Type I; D008274:Magnesium
keywords: Anterior cruciate ligament reconstruction; BMP-2; Fibrocartilaginous entheses; High-purity magnesium; Interference screw; VEGF