title: Polyelectrolyte Complex Carrier Enhances Therapeutic Efficiency and Safety Profile of Bone Morphogenetic Protein-2 in Porcine Lumbar Interbody Fusion Model.
abstract: METHODS
  Porcine lumbar interbody fusion model.
  
  
  OBJECTIVE
  This study evaluates the effect of polyelectrolyte complex (PEC) carrier in enhancing the therapeutic efficiency and safety profile of bone morphogenetic protein-2 (BMP-2) in a large animal model.
  
  
  BACKGROUND
  Extremely large amounts of BMP-2 are administered to achieve consistent spinal fusion, which has led to complications. Heparin-modified PEC carrying reduced BMP-2 doses of 0.5 μg was demonstrated to achieve consistent spinal fusion with reduction of complications in rodent model. The purpose of this study was to evaluate whether PEC could improve the therapeutic efficiency of BMP-2 in porcine model.
  
  
  METHODS
  Three-segment (L3-L6) anterior lumbar interbody fusions with instrumentation were performed on 6 pigs using 3 different doses of BMP-2, namely, (1) 50 μg, (2) 150 μg, and (3) 300 μg. The BMP-2 was delivered using heparin-modified alginate microbeads loaded into biodegradable cage. Fusion performance was evaluated after 3 months.
  
  
  RESULTS
  Manual palpation and micro-computed tomography showed consistent fusion in all experimental groups. Heterotopic bone formation beyond the cage implant area was more evident in group 2 and group 3 than in group 1. Similarly, superior bone microstructure was observed in the new bone with the lowered BMP-2 dose. Biomechanical evaluation revealed enhanced stiffness of the operated segments compared with nonoperated segments (P < 0.05). Mechanical stability was maintained despite dose reduction of BMP-2. Although the mineral apposition rate was higher in group 3, unsatisfactory bony microstructure with decreased trabecular number was observed in group 3 compared with group 1.
  
  
  CONCLUSIONS
  PEC carrying low doses of BMP-2 achieved consistent interbody fusion. We observed dose-related reduction in heterotopic ossification without compromising the stability of the fused segments. PEC carrier reduces the efficacious doses of BMP-2. This could enhance the safety profile of BMP-2 and reduce dose- and carrier-related complications.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore †Singapore Institute of Manufacturing Technology, A*STAR, Singapore ‡Institute of Medical Biology, A*STAR, Singapore §Singapore Bioimaging Consortium, A*STAR, Singapore ¶Institute of Materials Research and Engineering, A*STAR, Singapore; and ‖Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Sunny Akogwu
authors.initials: SA
authors.lastname: Abbah
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.forename: Raymond Wing Moon
authors.initials: RW
authors.lastname: Lam
authors.forename: Soo Yein
authors.initials: SY
authors.lastname: Toh
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cool
authors.forename: Kishore
authors.initials: K
authors.lastname: Bhakoo
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: James Cho Hong
authors.initials: JC
authors.lastname: Goh
authors.forename: Hee-Kit
authors.initials: HK
authors.lastname: Wong
mesh_terms: D020341:Absorbable Implants; D000464:Alginates / Q000737:chemistry; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D016723:Bone Remodeling / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006493:Heparin / Q000031:analogs & derivatives / Q000737:chemistry; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D009999:Ossification, Heterotopic / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D011108:Polymers / Q000737:chemistry*; D013123:Spinal Fusion / Q000009:adverse effects; D013314:Stress, Mechanical; D013552:Swine; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011108:Polymers; D006493:Heparin