title: Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-released microsphere: an experimental study on sheep model.
abstract: Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P < 0.05). These findings indicate that the SF microspheres containing a very low dose of rhBMP-2 improve fusion in sheep using BCP constructs.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, No 188 Shizi Street, Suzhou, 215006, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Yang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002130:Calcium Phosphates / Q000008:administration & dosage*; D005349:Fibroins / Q000008:administration & dosage*; D008159:Lumbar Vertebrae / Q000601:surgery*; D008863:Microspheres; D023421:Models, Animal; D011994:Recombinant Proteins / Q000008:administration & dosage; D012756:Sheep; D047011:Silk / Q000737:chemistry; D013123:Spinal Fusion
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D047011:Silk; D005349:Fibroins; C020243:calcium phosphate