title: Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics.
abstract: Reports on the local delivery of drug loaded injectable hydrogels for bone regeneration are currently limited. This study assessed the effect of controlled simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo. We successfully manufactured and evaluated thermo-sensitive poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and osteoblastic differentiation was analyzed after cultivation with the hydrogel extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in mineralization and osteogenic gene expression compared to the other two groups. Additionally, the characteristics of this composite in vivo were demonstrated using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA hydrogel showed increased new bone formation compared to samples treated with PLGA-PEG-PLGA and control samples. The results of this study suggest that SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Clinical Laboratory, the First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Liang-Wen
authors.initials: LW
authors.lastname: Chen
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mei
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D005786:Gene Expression Regulation / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D055114:X-Ray Microtomography
chemical_list: D000880:Anthraquinones; D003692:Delayed-Action Preparations; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011098:Polyglactin 910; D011092:Polyethylene Glycols; C010078:alizarin; D019821:Simvastatin; D000469:Alkaline Phosphatase
keywords: PLGA-PEG-PLGA; bone; drug delivery; simvastatin; thermo-sensitive