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Heparin-Based Polyelectrolyte Complex Enhances the Therapeutic Efficacy of Bone Morphogenetic Protein-2 for Posterolateral Fusion in a Large Animal Model

Wang, Ming MD, MRCS; Lam, Raymond W.M. PhD; Abbah, Sunny A. MD, PhD; Hu, Tao MD; Toh, Soo Y. Bsc; Cool, Simon PhD∗,†; Bhakoo, Kishore PhD∗,‡; Li, Jun PhD§,¶; Goh, James C.H. PhD∗,¶; Wong, Hee-Kit FRCS

doi: 10.1097/BRS.0000000000001543
BASIC SCIENCE
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Study Design. The study was based on porcine posterolateral fusion model.

Objective. The study aims to prove that polyelectrolyte complex (PEC) carrier could enhance the efficacy and safety profile of bone morphogenetic protein-2 (BMP-2).

Summary of Background Data. BMP-2 was introduced to enhance posterolateral fusion; however, extremely high doses of this molecule were often used which contributed to various complications. This was attributed to the poor modulation capacity of the traditional carrier absorbable collagen sponge (ACS). To reduce the efficacious dose of BMP-2 and its associated complications, heparin-based PEC was introduced.

Methods. L3/L4 and L5/L6 two-level posterolateral spinal fusion was performed on six pigs using two doses of BMP-2 with PEC or ACS: (1) PEC with 800 μg BMP-2 (n = 2); (2) PEC with 400 μg BMP-2 (n = 2); (3) ACS with 800 μg BMP-2 (n = 1); (4) ACS with 400 μg of BMP-2 (n = 1). The construct was loaded into a rigid bioabsorbable cage for implantation. Fusion rate and quality were assessed 2 months after operation.

Results. Manual palpation revealed successful fusion in all groups. Radiological fusion score of PEC groups was, however, higher than that of ACS groups. The newly formed bone in PEC groups appeared to be well integrated into the native bone with no overgrowth into the adjacent structure. On comparison, in ACS groups, large gaps were observed between the newly formed bone and the fusion bed with heterotopic ossification into the psoas muscle. The microarchitecture on the newly formed bone in PEC groups was superior to that in ACS groups, which was demonstrated by higher three-dimensional parameters.

Conclusion. The present study demonstrated that BMP-2 delivered by PEC induced successful posterolateral fusion in porcine model. The efficacy of BMP-2 was improved and bony overgrowth was reduced. The microarchitecture of BMP-2–induced bone tissue was also enhanced by PEC.

Level of Evidence: N/A

Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore

Institute of Medical Biology

Singapore Bioimaging Consortium

§Institute of Materials Research and Engineering, ASTAR

Department of Bioengineering, Faculty of Engineering, National University of Singapore.

Address correspondence and reprint requests to Hee-Kit Wong, FRCS, University Orthopaedics, Hand and Reconstructive Microsurgery Cluster, Level 11, NUHS Tower Block, 1E Kent Ridge Rd, Singapore 119228; E-mail: heekit_wong@nuhs.edu.sg

Received 9 October, 2015

Revised 12 January, 2016

Accepted 16 February, 2016

The device(s)/drug(s) that is/are the subject of this manuscript is/are not intended for human use.

ASTAR BMRC Grant 09/1/21/19/601 funds were received in support of this work.

Relevant financial activities outside the submitted work: consultancy.

Copyright © 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.