The effect of local simvastatin application on critical size defects in the diabetic rats

Ezirganlı, Şeref; Kazancioğlu, Hakkı Oğuz; Mihmanlı, Ahmet; Aydın, Mehmet; Sharifov, Rasul; Alkan, Alpay

doi:10.1111/clr.12177

Cited by 36 publications

(42 citation statements)

References 53 publications

(52 reference statements)

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“…20 In contrast, local delivery of SIM has been reported to have a positive effect on bone formation. [21][22][23][24] Furthermore, Cui et al reported that SIM can mobilize mesenchymal stem cells migrating to bone defects. Because of these properties, SIM can be used as an osteogenic growth factor.…”

Section: Introductionmentioning

confidence: 99%

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Zhang

Han

et al. 2016

IJN

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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.

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Section: Introductionmentioning

confidence: 99%

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Zhang

Han

et al. 2016

IJN

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“…Various studies have investigated local delivery of statins to increase bone healing and reported that statins have local beneficial effects. 5,[19][20][21][22][23][24][25][26] However, some studies showed adverse effects. 21,24,27 Thylin et al and Stein et al reported that local application of simvastatin 2.2 mg caused inflammation in soft tissue in a rat calvarial bone defect model and in mandible bone.…”

Section: Discussionmentioning

confidence: 99%

“…15,18 In contrast, local delivery of statins has been reported to have a positive effect on bone formation. 5,[19][20][21][22][23][24][25][26] Mukozawa et al reported that simvastin with hydrogel and atelocollagen sponge (ACS) implants enhanced critical-sized nasal defects in rabbits. 25 Ezirganli et al also indicated that local application of simvastatin enhanced healing of criticalsized bone defects in diabetic rats.…”

mentioning

confidence: 99%

“…25 Ezirganli et al also indicated that local application of simvastatin enhanced healing of criticalsized bone defects in diabetic rats. 26 However, some studies demonstrated that local delivery of statins without control of the optimal release concentration induces an inflammatory response. 21,24,27 Therefore, this study aimed to develop a suitable carrier for controlling the release of simvastatin in an effective and nontoxic concentration range over a time duration that is appropriate to enhance bone healing.…”

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confidence: 99%

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Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

Tai¹,

Fu²,

Wang³

et al. 2013

IJN

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“…In those that used rat, higher doses of Simvastatin including 1, 5 and 25 mg/scaffold or mg/rat BW were much more effective than those that used lower doses (between 0.001 and 2.2 mg/rat BW ) and no differences were observed between the results of those that used higher doses. 25,35,38 It has been shown that low dose of Simvastatin (0.5 mg) reduces bone density on day 30 while after 60 days of injury, regardless of the dose, Simvastatin both at 0.5 and 2.2 mg/rat BW retards bone healing. 58 In rabbits, 2.5 and 5 mg Simvastatin/scaffold or/rabbit BW were the most effective doses responsible for bone regeneration.…”

Section: Dosementioning

confidence: 99%

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

Moshiri

Sharifi

Oryan

2016

Clin Exp Pharma Physio

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SUMMARYSimvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.

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The effect of local simvastatin application on critical size defects in the diabetic rats

Abstract: The local simvastatin application enhanced healing of the bone defects in the diabetic rat model CSDs.

Cited by 36 publications

References 53 publications

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

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