title: Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament.
abstract: The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL) reconstruction. But the biological graft-bone healing still remains a problem. Previous studies have shown that simvastatin (SIM) stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low-dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET) artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen-coated PET scaffolds (COL/PET) and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET) proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells' osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft-bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM-sustained release from SIM/COL/PET promoted the graft-bone healing via its effect on both angiogenesis and osteogenesis. This study suggested that collagen containing low-dose SIM microsphere coating on the surface of PET artificial ligaments could be potentially applied for ACL reconstruction.
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Peng
authors: P
authors: Zhang
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, School of Medicine, Tongji University, Shanghai, People's Republic of China.
authors: Fei
authors: F
authors: Han
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Yunxia
authors: Y
authors: Li
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Jiwu
authors: J
authors: Chen
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Tianwu
authors: T
authors: Chen
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Yunlong
authors: Y
authors: Zhi
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Jia
authors: J
authors: Jiang
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, School of Medicine, Tongji University, Shanghai, People's Republic of China.
authors: Chao
authors: C
authors: Lin
authors: Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Shiyi
authors: S
authors: Chen
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, School of Medicine, Tongji University, Shanghai, People's Republic of China.
authors: Peng
authors: P
authors: Zhao
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction / Q000295:instrumentation / Q000379:methods*; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015675:Osteocalcin / Q000235:genetics; D011093:Polyethylene Terephthalates; D011817:Rabbits; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D011093:Polyethylene Terephthalates; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D003094:Collagen; D019821:Simvastatin
keywords: biocompatibility; controlled release; graft–bone healing; ligament reconstruction; simvastatin