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Updated: Apr 14, 2026
Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery
Published on: August 22, 2016
Polyelectrolyte Complex Carrier Enhances Therapeutic Efficiency and Safety Profile of Bone Morphogenetic Protein-2 in
Ming Wang1, Sunny Akogwu Abbah, Tao Hu
1*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.
Study Design:
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.
Summary Of Background Data:
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.
Conclusion:
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.
Level Of Evidence:
N/A.
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