title: Bone morphogenetic protein-2-encapsulated grafted-poly-lactic acid-polycaprolactone nanoparticles promote bone repair.
abstract: The aim of this study is to test the efficacy of a novel tissue-engineered bone in repairing bone defects, using poly-lactic-acid-polycaprolactone (PLA-PCL) scaffolding seeded with PEG-bone morphogenetic protein-2 (BMP-2)-transfected rBMSCs (rabbit bone marrow stromal cells). The rBMSCs were transfected with PEG/BMP-2 or liposome/BMP-2, and then implanted into a PLA-PCL tissue-engineered bone. The protein level of BMP-2 was assessed by Western blot analysis and immunohistochemistry. ELISA was used to measure the amount of BMP-2 secreted in the culture media. The mRNA level of BMP-2 and osteocalcin was assayed quantitatively by real-time PCR. The middle portion of the bilateral radius in New Zealand rabbits was excised and implanted with tissue-engineered bone, and the modified areas were monitored by X-ray, hematoxylin-eosin staining, and immunohistochemistry staining of BMP-2. PEG-BMP-2 nanoparticles (NPs) and BMP-2-loaded PEG-PLA-PCL tissue-engineered bones were successfully constructed. The novel PEG-PLA-PCL NPs/DNA complex was a superior option for transfecting BMP-2 in rBMSCs compared to normal liposomes Moreover, the mRNA level of osteocalcin and alkaline phosphatase activity was also elevated upon transfection of BMP-2-encapsulated NPs. In vivo implants with BMP-2-carried tissue-engineered bone exhibited dramatic augmentation of BMP-2 and effective bone formation in the rabbit ectopic model. The PEG-PLA-PCL NPs/BMP-2 complex had an advantageous effect on bone repair, which provided an important theoretic basis for potential clinical treatments.
authors.affiliation: Department of Traumatic Orthopaedic, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, 110004, Liaoning Province, China, xiaojunxucc@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Ding
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000235:genetics*; D002214:Capsules; D002453:Cell Cycle; D002469:Cell Separation; D005786:Gene Expression Regulation; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles; D015675:Osteocalcin / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D012038:Regeneration; D013977:Tibia / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D023822:Tissue Engineering; D014057:Tomography, X-Ray Computed; D014162:Transfection
chemical_list: D055396:Bone Morphogenetic Protein 2; D002214:Capsules; D011091:Polyesters; D011108:Polymers; D015675:Osteocalcin; C016240:polycaprolactone; D019344:Lactic Acid; C033616:poly(lactide)