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

Tai, I-Chun; Fu, Yin‐Chih; Wang, Chih-Kuang; Chang, Je-Ken; Ho, Mei-Ling

doi:10.2147/ijn.s48694

Cited by 35 publications

(17 citation statements)

References 39 publications

(71 reference statements)

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“…Studies have reported that statins act in the stimulation of bone tissue. 4 , 10 This action occurs due to the stimulation of bone morphogenic protein (BMP-2), which causes osteoblastic proliferation and differentiation, resulting in a greater and better bone tissue formation. According to Anbinder et al, 11 all statins stimulate BMP-2, except pravastatin.…”

Section: Discussionmentioning

confidence: 99%

Effects of simvastatin associated with exercise on the mechanical resistance of muscle and bone in rats

Yamanaka

Ribeiro

Yanagihara

et al. 2018

Revista Brasileira de Ortopedia (English Edition)

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ObjectiveThe aim of the present study was to evaluate the influence of simvastatin on mechanical properties of muscle and bone in hypercholesterolemic rats submitted to physical exercise.MethodsTen male Wistar rats were submitted to a high-fat diet rich in cholesterol for 90 days. The animals were then divided into two groups: animals treated with physical exercise (EG) and animals treated with physical exercise and simvastatin (ESG). Protocols for physical exercise in water and simvastatin administration were performed for eight weeks. After this period, the animals were euthanized; the left tibia and right gastrocnemius muscle were dissected for mechanical analysis, and the right tibia for densitometry. The data were analyzed using Student's t-test, considering a level of significance of 5%.ResultsThe comparison of maximum load and stiffness revealed no significant differences between the groups for both the tibia (p = 0.851 and p = 0.259) and the gastrocnemius (p = 0.911 and p = 0.083). The tibia BMD also showed no significant difference between the groups (p = 0.803).ConclusionSimvastatin had no negative effects on mechanical properties in tibia and gastrocnemius of hypercholesterolemic rats submitted to physical exercise.

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Section: Discussionmentioning

confidence: 99%

Effects of simvastatin associated with exercise on the mechanical resistance of muscle and bone in rats

Yamanaka

Ribeiro

Yanagihara

et al. 2018

Revista Brasileira de Ortopedia (English Edition)

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“…Synthetic polymers are another alternative to naturally derived polymers and have the advantage of being highly modifiable and tunable, though they also lack natural environmental cues to direct tissue growth. Poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) are common synthetic polymer carriers for statins, either as microparticles or a membrane [103,124–126]. Stein et al combined hydrogel and poly(lactic acid) to locally deliver simvastatin to the lateral aspect of the rat mandible and investigated dose response, finding that a low dose applied locally could achieve bone growth while avoiding the inflammation that occurs with administration of high doses [19].…”

Section: Statins Bone Regeneration and Bone Tissue Engineeringmentioning

confidence: 99%

Novel applications of statins for bone regeneration

Shah

Werlang

Kasper

et al. 2014

National Science Review

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The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering.

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“…Several in vitro studies indicated that statins can increase the expression of osteogenic marker genes other than BMP-2, including alkaline phosphatase, runt-related transcription factor 2 (RUNX-2), osteopontin, and osteocalcin, in osteoblastic cells and bone marrow-derived cells [17,18]. We demonstrated an effect of controlled release of simvastatin (SIM) from poly (lactic-co-glycolic acid)/hydroxyapatite) (PLGA/HAp) microspheres in vitro and improved bone healing of necrotic bone grafts in vivo [19,20]. We concluded that calcium phosphate bioceramics combined with simvastatin (SIM) microcarriers can stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo.…”

Section: Introductionmentioning

confidence: 99%

Combination of a Bioceramic Scaffold and Simvastatin Nanoparticles as a Synthetic Alternative to Autologous Bone Grafting

Wang

Lin

et al. 2018

IJMS

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The fragile nature of porous bioceramic substitutes cannot match the toughness of bone, which limits the use of these materials in clinical load-bearing applications. Statins can enhance bone healing, but it could show rhabdomyolysis/inflammatory response after overdosing. In this study, the drug-containing bone grafts were developed from poly(lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles encapsulating simvastatin (SIM) (SIM-PP NPs) loaded within an appropriately mechanical bioceramic scaffold (BC). The combination bone graft provides dual functions of osteoconduction and osteoinduction. The mechanical properties of the bioceramic are enhanced mainly based on the admixture of a combustible reverse-negative thermoresponsive hydrogel (poly(N-isopropylacrylamide base). We showed that SIM-PP NPs can increase the activity of alkaline phosphatase and osteogenic differentiation of bone marrow stem cells. To verify the bone-healing efficacy of this drug-containing bone grafts, a nonunion radial endochondral ossification bone defect rabbit model (N = 3/group) and a nonunion calvarial intramembranous defect Sprague Dawley (SD) rat model (N = 5/group) were used. The results indicated that SIM-PP NPs combined with BC can improve the healing of nonunion bone defects of the radial bone and calvarial bone. Therefore, the BC containing SIM-PP NPs may be appropriate for clinical use as a synthetic alternative to autologous bone grafting that can overcome the problem of determining the clinical dosage of simvastatin drugs to promote bone healing.

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

Cited by 35 publications

References 39 publications

Effects of simvastatin associated with exercise on the mechanical resistance of muscle and bone in rats

Effects of simvastatin associated with exercise on the mechanical resistance of muscle and bone in rats

Novel applications of statins for bone regeneration

Combination of a Bioceramic Scaffold and Simvastatin Nanoparticles as a Synthetic Alternative to Autologous Bone Grafting

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