title: Repair of bone defect in femoral condyle using microencapsulated chitosan, nanohydroxyapatite/collagen and poly(L-lactide)-based microsphere-scaffold delivery system.
abstract: Bone repair ability of microencapsulated chitosan, nanohydroxyapatite/collagen (nHAC), and poly(L-lactide) (PLLA)-based microsphere-scaffold delivery system was investigated in present research, with nHAC/PLLA composite scaffold as a control. Chitosan microspheres (CMs) encapsulated with bone morphogenetic protein-2-derived synthetic peptide were incorporated into nHAC and PLLA-based matrix via a thermally induced phase separation method, in which dioxane was used as the solvent for PLLA. Compared with the rapid release from CMs, the synthetic peptide was delivered from CMs/nHAC/PLLA microsphere-scaffold composite in a temporally controlled manner, depending on the degradation of both incorporated CMs and PLLA matrix. MC3T3-E1 osteoblastic cells were seeded into nHAC/PLLA and CMs/nHAC/PLLA scaffolds, respectively, and in vitro cytocompatibility was tested by scanning electron microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results indicated that, with the appearance of CMs in microsphere-scaffold composite, the osteoblasts exhibit better morphology and proliferation ability. In vivo tissue compatibility was evaluated by transplanting the scaffolds into rabbit femoral condyles with a defect 6 mm in diameter. After implanting for 4, 8, and 12 weeks, respectively, radiographic and histological observation revealed that the CMs/nHAC/PLLA composite can accelerate the regeneration of cancellous bone defect as compared with the nHAC/PLLA scaffold. The results demonstrated that the CMs/nHAC/PLLA possesses better biocompatibility, which should be attributed to both the incorporated chitosan component and the encapsulated bioactive synthetic peptide. The promising CMs/nHAC/PLLA microsphere-scaffold composite can be used as delivery system for multiple bioactive factors or as inductive implant scaffold for bone regeneration.
authors.affiliation: Laboratory of Advanced Materials, Department of Materials Science and Engineering, Tsinghua University, Beijing, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Niu
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.forename: Xinhui
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Jiangxue
authors.initials: J
authors.lastname: Wang
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Sha
authors.forename: Qingling
authors.initials: Q
authors.lastname: Feng
mesh_terms: D016475:3T3 Cells; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D005269:Femur / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008863:Microspheres; D010006:Osteoblasts / Q000166:cytology; D011091:Polyesters / Q000737:chemistry*; D011817:Rabbits; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D011091:Polyesters; C509317:nano-hydroxyapatite-collagen; C033616:poly(lactide); D003094:Collagen; D048271:Chitosan; D017886:Durapatite