title: Local administration of low-dose simvastatin-conjugated gelatin hydrogel for tendon-bone healing in anterior cruciate ligament reconstruction.
abstract: Anterior cruciate ligament (ACL) reconstruction with the hamstring tendon graft takes a long time, as the tendon graft needs to heal at the site of the bone-tendon integration in the created bone tunnels. Several reports have shown the therapeutic effects of simvastatin on bone formation with neovascularization. The aim of this study was to test the hypothesis that enhanced angiogenesis and osteogenesis by locally applied simvastatin promotes tendon-bone healing after ACL reconstruction. Rabbits received ACL reconstruction with hamstring tendon graft and were implanted with either simvastatin-conjugated gelatin hydrogel or gelatin hydrogel alone in their bone tunnels, and then bone regeneration and neovascularization at tendon-bone interface and biomechanical properties were assessed. Histological analysis at week 2 demonstrated that tendon-bone healing was significantly greater with angiogenesis and osteogenesis in the simvastatin-treated group than in the control group. Computed tomography at weeks 2 and 4 showed a significantly smaller tibial bone tunnel in the simvastatin-treated group. Biomechanical testing at week 2 demonstrated a significant increase in ultimate failure load in the simvastatin-treated group. This study suggested that local administration of low-dose simvastatin-conjugated gelatin hydrogel promotes the tendon-bone healing via its effect on both angiogenesis and osteogenesis at an early phase in a rabbit model, but does not affect biomechanical property in long-term after ACL reconstruction.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe- city 650-0017, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Oka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Kubo
authors.forename: Takehiko
authors.initials: T
authors.lastname: Matsushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Tokio
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods*; D005780:Gelatin / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D011817:Rabbits; D019821:Simvastatin / Q000737:chemistry* / Q000627:therapeutic use*; D013710:Tendons / Q000166:cytology* / Q000187:drug effects / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D019821:Simvastatin