Enhancement of osteoinduction by continual simvastatin release from poly(lactic-co-glycolic acid)-hydroxyapatite-simvastatin nano-fibrous scaffold.
Simvastatin is considered as a stimulator for bone formation. However, the half-life for simvastatin is generally 2 hours, which means, it is difficult to maintain biologically active simvastatin in vivo. To overcome this limitation, we created a system to slowly release simvastatin in vitro and in vivo. We constructed a poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffold to carry simvastatin. Releasing assays showed that simvastatin was released from poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin quickly within - 15 days, and small amounts continued to be released through day 56 (experiments terminated). MTT assays demonstrated that both poly(lactic-co-glycolic acid)/hydroxyapatite and poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin promoted MC3T3-E1 cell proliferation. However, Alkaline phosphatase assays showed that only poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold significantly promoted the osteogenic differentiation of MC3T3-E1 cells in vitro on day 14. To further test in vivo, we created calvaria bone defect models and implanted either poly(lactic-co-glycolic acid)/hydroxyapatite or poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin. After 4 or 8 weeks post-implantation, the results indicated that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold induced bone formation more efficiently than poly(lactic-co-glycolic acid)/hydroxyapatite alone. Our data demonstrates that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin has the potential to aid in healing bone defects and promoting bone regeneration in the future although we still need to optimize this complex to efficiently promote bone regeneration.
Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun 130021, PR China.
Liming
L
Jiang
Haizhu
H
Sun
Anliang
A
Yuan
Kai
K
Zhang
Daowei
D
Li
Chen
C
Li
Ce
C
Shi
Xiangwei
X
Li
Kai
K
Gao
Changyu
C
Zheng
Bai
B
Yang
Hongchen
H
Sun
D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage*; D012887:Skull Fractures / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D053769:Nanocapsules; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite; D019821:Simvastatin