Fusion Performance of Low-Dose Recombinant Human Bone... : Spine (original) (raw)

Basic Science

Fusion Performance of Low-Dose Recombinant Human Bone Morphogenetic Protein 2 and Bone Marrow-Derived Multipotent Stromal Cells in Biodegradable Scaffolds

A Comparative Study in a Large Animal Model of Anterior Lumbar Interbody Fusion

Abbah, Sunny A. MBBS, PhD*; Lam, Christopher X.F. PhD†; Ramruttun, Amit K. BSc*; Goh, James C.H. PhD*,†; Wong, Hee-Kit FRCS*

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

†Division of Bioengineering, Faculty of Engineering, National University of Singapore.

Address correspondence and reprint requests to Hee-Kit Wong, MD, University Orthopaedics, Hand and Reconstructive Microsurgery Cluster, Level 11, NUHS Tower Block, 1E Kent Ridge Rd, Singapore 119228; E-mail: [email protected].

Acknowledgment date: October 18, 2010. Revision date: January 23, 2011. Acceptance date: February 21, 2011.

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States.

Institutional funds were received in support of this work.

No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

This work was supported by a grant from the Biomedical Research Council, A*Star Singapore (Grant 03/1/21/18/218).

Study Design.

A large animal study comparing interbody fusion of a bioresorbable scaffold loaded with either low-dose recombinant human bone morphogenetic protein 2 (rhBMP-2) or bone marrow-derived multipotent stromal cells (BMSCs).

Objective.

To compare the quality of fusion resulting from implantation of medical grade poly (∊-caprolactone)-20% tricalcium phosphate (mPCL/TCP) scaffolds and two different bone growth stimulating agents.

Summary of Background Data.

Nondegradable cages have been used for interbody fusion with good results. However, the overall advantage of lifelong implantation of a nondegradable device remains a subject of ongoing debate. The use of bioresorbable scaffolds might offer superior alternatives. In this study, we evaluated the quality of fusion obtained with two potential bone graft substitutes.

Methods.

Eleven Yorkshire pigs underwent a bisegmental (L2/L3; L4/L5) anterior lumbar interbody fusion (ALIF) in four groups, namely: (1) mPCL/TCP + 0.6mg rhBMP-2; (2) mPCL/TCP + BMSCs; (3) mPCL/TCP (negative control); and (4) autologous bone grafts (positive control).

Results.

The mean radiographic scores at 9 months were 3.0, 1.7, 1.0, and 1.8 for groups 1 to 4, respectively. The bone volume fraction of group 1 was two-folds higher than group 2. Histology, micro-computed tomographic scanning and biomechanical evaluation demonstrated solid and comparable fusion between groups 1 and 4. However, group 2 showed inferior quality of fusion when compared with groups 1 and 4 while group 3 showed no fusion even at 9 months. In addition, there was no evidence of implant rejection, chronic inflammation or any other complications.

Conclusion.

mPCL/TCP scaffolds loaded with low-dose rhBMP-2 is comparable to autograft bone as a bone graft substitute in this large animal ALIF model. Although BMSCs lagged behind autograft bone and rhBMP-2, evidence of bone ingrowth in this group warrants further investigation. Our results suggest that mPCL/TCP scaffolds loaded with rhBMP-2 or BMSCs may be a viable alternative to conventional cages and autograft bone.