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A synthetic retinoic acid receptor γ antagonist (7C)-loaded nanoparticle enhances bone morphogenetic protein-induced bone regeneration in a rat spinal fusion model – Lumbar Fusion

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The article discusses a study that aimed to find a solution to the side effects caused by the high doses of bone morphogenetic proteins (BMPs) used in clinical settings. The researchers synthesized a nanoparticle called 7C, which is loaded with a retinoic acid receptor γ antagonist. They tested the potential application of this nanoparticle in BMP-based bone regeneration therapy using a rat spinal fusion model. The study found that the combined use of 7C-NP with BMP-2 increased the spinal fusion rate and new bone volume without deteriorating the quality of the newly formed bone. This suggests that 7C-NP has the potential to efficiently regenerate bone using lower doses of BMP-2, thus reducing the side effects associated with high doses

Summarised by Mr Mo Akmal – Lead Spinal Surgeon
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Published article

S: The combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone.

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Spine J. 2023 Dec 11:S1529-9430(23)03539-8. doi: 10.1016/j.spinee.2023.11.021. Online ahead of print.ABSTRACTBACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced.PURPOSE:,

Spine J. 2023 Dec 11:S1529-9430(23)03539-8. doi: 10.1016/j.spinee.2023.11.021. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced.

PURPOSE: To address this problem, we synthesized 7C, a retinoic acid receptor γ antagonist-loaded nanoparticle (NP), and investigated its potential application in BMP-based bone regeneration therapy using a rat spinal fusion model.

STUDY DESIGN: An experimental animal study.

METHODS: Fifty-three male 8-week-old Sprague-Dawley rats underwent posterolateral spinal fusion and were divided into the following five treatment groups: (1) no recombinant human (rh)BMP-2 and blank-NP (Control), (2) no rhBMP-2 and 1 μg 7C-NP (7C group), (3) low-dose rhBMP-2 (0.5 μg) and 1 μg blank-NP (L-BMP group), (4) low-dose rhBMP-2 (0.5 μg) and 1 μg 7C-NP (L-BMP + 7C group), and (5) high-dose rhBMP-2 (5.0 μg) and 1 μg blank-NP (H-BMP group). Micro-computed tomography and histological analysis were performed 2 and 6 weeks after the surgery, RESULTS: The spinal fusion rates of the Control and 7C groups were both 0%, and those of the L-BMP, L-BMP + 7C, and H-BMP groups were 55.6%, 94.4%, and 100%, respectively. The L-BMP + 7C group markedly promoted cartilaginous tissue formation during BMP-induced endochondral bone formation that resulted in a significantly better spinal fusion rate and bone formation than in the L-BMP group. Although spinal fusion was slower in the L-BMP + 7C group, the L-BMP + 7C group formed a spinal fusion mass with better bone quality than the spinal fusion mass in the H-BMP group.

S: The combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone.

CLINICAL SIGNIFICANCE: 7C-NP potentiates BMP-2-induced bone regeneration and has the potential for efficient bone regeneration with low-dose BMP-2, which can reduce the dose-dependent side effects of BMP-2 in clinical settings.

PMID:38092193 | DOI:10.1016/j.spinee.2023.11.021

The London Spine Unit : most advanced treatment clinic in UK

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A synthetic retinoic acid receptor γ antagonist (7C)-loaded nanoparticle enhances bone morphogenetic protein-induced bone regeneration in a rat spinal fusion model

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Spine J. 2023 Dec 11:S1529-9430(23)03539-8. doi: 10.1016/j.spinee.2023.11.021. Online ahead of print.ABSTRACTBACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced.PURPOSE:

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