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Tissue Eng Part A. 2019 Feb 6. doi: 10.1089/ten.TEA.2018.0281. [Epub ahead of print]

Bone Regeneration by Controlled Release of BMP-2: A Rabbit Spinal Fusion Chamber Molecular Study.

Author information

1
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore.
2
Shanghai East Hospital, Tongji University School of Medicine., Department of Spine Surgery, Shanghai, China ; 52486740@qq.com.
3
National University Singapore Yong Loo Lin School of Medicine, 63751, Singapore, Singapore.
4
National University Singapore Yong Loo Lin School of Medicine, 63751, NUS Tissue Engineering Program (NUSTEP), Singapore, Singapore ; csimnj@nus.edu.sg.
5
National University Singapore Yong Loo Lin School of Medicine, 63751, NUS Tissue Engineering Program (NUSTEP), Singapore, Singapore ; dosyz@nus.edu.sg.
6
National University Singapore Yong Loo Lin School of Medicine, NUS Tissue Engineering Program (NUSTEP), Singapore, Singapore ; doslwmr@nus.edu.sg.
7
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore ; dosrak@nus.edu.sg.
8
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore ; dosrxf@nus.edu.sg.
9
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore ; Felly_ng@yahoo.com.
10
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore ; ming_wang@nuhs.edu.sg.
11
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore ; e0001883@u.nus.edu.
12
Temasek Polytechnic, 63234, School of Engineering, Singapore, Singapore ; kimcheng@tp.edu.sg.
13
Temasek Polytechnic, 63234, School of Engineering, Singapore, Singapore ; kaithong@tp.edu.sg.
14
Stanford University, Department of Orthopedic Surgery, Stanford, California, United States ; goodbone@stanford.edu.
15
National University of Singapore, Department of Bioengineering, Singapore, Singapore ; biegohj@nus.edu.sg.
16
National University Singapore Yong Loo Lin School of Medicine, 63751, Department of Orthopedic Surgery, Singapore, Singapore ; doswhk@nus.edu.sg.

Abstract

Recombinant human bone morphogenetic protein (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) has led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion. The molecular events underlying controlled release and their effects on spinal fusion remains unknown. In this study, a rabbit interbody spinal fusion chamber was designed to provide a controlled environment for profiling molecular events during the fusion process. Study groups included Group 1, PEC with 100µg rhBMP-2; Group 2, ACS with 100µg rhBMP-2; Group 3, ACS with 300µg rhBMP-2; Group 4, autologous bone graft and Group 5, empty chamber. Manual palpation, µCT and histological analysis showed that Group 1 and 3 achieved bone fusion, while the other groups showed no signs of fusion. Gene expression profiling showed robust induction of osteogenic markers in Groups 1 and 3, with modulated early induction of inflammatory genes in the PEC group. Delivery of 100µg rhBMP-2 with ACS (Group 2) resulted in less upregulation of osteogenic genes, increased inflammatory genes expression, and upregulation of osteoclastic genes compared to Group 1. These results suggest that the manner of BMP-2 release at the interbody spinal defect site could dictate the balance of in-situ osteogenic and anti-osteogenic activities, affecting fusion outcomes. The molecular evidence supports PEC for sustained release of BMP-2 for spinal interbody fusion, and the feasibility of employing this novel interbody spinal fusion chamber for future molecular studies.

PMID:
30727849
DOI:
10.1089/ten.TEA.2018.0281

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