Journal article
A BMP/Activin A Chimera Induces Posterolateral Spine Fusion in Nonhuman Primates at Lower Concentrations Than BMP-2
Journal of bone and joint surgery. American volume, Vol.103(16), e64
08/18/2021
DOI: 10.2106/JBJS.20.02036
PMID: 33950879
Abstract
Background: Supraphysiologic bone morphogenetic protein (BMP)-2 concentrations are required to induce spinal fusion. In this study, a BMP-2/BMP-6/activin A chimera (BV-265), optimized for BMP receptor binding, delivered in a recombinant human collagen:CDHA [calcium-deficient hydroxyapatite] porous composite matrix (CM) or bovine collagen:CDHA granule porous composite matrix (PCM), engineered for optimal BV-265 retention and guided tissue repair, was compared with BMP-2 delivered in a bovine absorbable collagen sponge (ACS) wrapped around a MASTERGRAFT Matrix (MM) ceramic-collagen rod (ACS:MM) in a nonhuman primate noninstrumented posterolateral fusion (PLF) model. Methods: In vivo retention of I-125-labeled-BV-265/CM or PCM was compared with I-125-labeled-BMP-2/ACS or BMP-2/buffer in a rat muscle pouch model using scintigraphy. Noninstrumented PLF was performed by implanting CM, BV-265/CM, BV-265/PCM, or BMP-2/ACS:MM across L3-L4 and L5-L6 or L3-L4-L5 decorticated transverse processes in 26 monkeys. Computed tomography (CT) images were acquired at 0, 4, 8, 12, and 24 weeks after surgery, where applicable. Manual palpation, mu CT (microcomputed tomography) or nCT (nanocomputed tomography), and histological analysis were performed following euthanasia. Results: Retention of I-125-labeled-BV-265/CM was greater than BV-265/PCM, followed by BMP-2/ACS and BMP-2/buffer. The CM, 0.43 mg/cm(3) BMP-2/ACS:MM, and 0.05 mg/cm(3) BV-265/CM failed to generate PLFs. The 0.15-mg/cm(3) BV-265/CM or 0.075-mg/cm(3) BV-265/PCM combinations were partially effective. The 0.25-mg/cm(3) BV-265/CM and 0.15 and 0.3-mg/cm(3) BV-265/PCM combinations generated successful 2-level PLFs at 12 and 24 weeks. Conclusions: BV-265/CM or PCM can induce fusion in a challenging nonhuman primate noninstrumented PLF model at substantially lower concentrations than BMP-2/ACS:MM.
Details
- Title: Subtitle
- A BMP/Activin A Chimera Induces Posterolateral Spine Fusion in Nonhuman Primates at Lower Concentrations Than BMP-2
- Creators
- Howard J. Seeherman - Orthoped Res & Pharmaceut Dev Consultant, Cambridge, MA 02138 USAChristopher G. Wilson - Bioventus LLC, Bioventus Surg, Boston, MA USAEric J. Vanderploeg - Bioventus LLC, Bioventus Surg, Boston, MA USAChristopher T. Brown - Bioventus LLC, Bioventus Surg, Boston, MA USAPablo R. Morales - Mannheimer Fdn Inc, Homestead, FL USADouglas C. Fredricks - University of Iowa, Carver College of MedicineJohn M. Wozney - Orthoped Res & Pharmaceut Dev Consultant, Hudson, MA USA
- Resource Type
- Journal article
- Publication Details
- Journal of bone and joint surgery. American volume, Vol.103(16), e64
- DOI
- 10.2106/JBJS.20.02036
- PMID
- 33950879
- NLM abbreviation
- J Bone Joint Surg Am
- ISSN
- 0021-9355
- eISSN
- 1535-1386
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 19
- Grant note
- Bioventus LLC
- Language
- English
- Date published
- 08/18/2021
- Academic Unit
- Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center
- Record Identifier
- 9985034987102771
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