A BMP/Activin A Chimera Induces Posterolateral Spine Fusion in Nonhuman Primates at Lower Concentrations Than BMP-2

Seeherman, Howard; Wilson, Christopher G.; Vanderploeg, Eric J.; Brown, Christopher T.; Morales, Pablo; Fredricks, Douglas C; Wozney, John M.

doi:10.2106/jbjs.20.02036

Cited by 3 publications

(2 citation statements)

References 88 publications

(234 reference statements)

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“…Our group previously reported that 3 μg/mL rhBMP2 doped nHAp-PEG/PLA presented similar spinal fusion rate and increased bone volume on week 8 comparing to higher dose (10 μg/mL doped nHAp-PEG/PLA) by manual palpation, μCT and histology when applied in vivo to lumbar 4-5 vertebrae rat PLSF model. Our findings were in line with a recent study 14 that evaluated fusion in non-human primates. Our dose window is in line with previous in vitro studies [21][22][23]28,29,31,32 revealing that optimal beneficial osteogenic effect of rhBMP2 takes place within a very tight dose window that would cause no inflammation but osteoinduction when applied to in vivo setting including lumbar spinal fusion model.…”

Section: Discussionsupporting

confidence: 93%

“…Recent research focused on decreasing the dose. 13 A current study 14 delivered BMP2/BMP6/activin A chimera with in a recombinant human collagen plus calcium‐deficient hydroxyapatite porous composite matrix in monkeys for PLSF to overcome problems of supraphysiologic BMP2 concentrations. BMP2 combined with synthetic grafts including polymers, 15 , 16 , 17 bioceramics, 18 , 19 bioactive glass 20 and their composites 21 , 22 , 23 could facilitate adequate PLSF.…”

Section: Introductionmentioning

confidence: 99%

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A pilot study: Nano‐hydroxyapatite‐PEG/PLA containing low dose rhBMP2 stimulates proliferation and osteogenic differentiation of human bone marrow derived mesenchymal stem cells

et al. 2023

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BackgroundBone morphogenetic protein 2 (BMP2) can enhance posterolateral spinal fusion (PLSF). The minimum effective dose that may stimulate mesenchymal stem cells however remains unknown. Nano‐hydroxyapatite (nHAp) polyethylene glycol (PEG)/polylactic acid (PLA) was combined with recombinant human BMP2 (rhBMP2). We in vitro evaluated proliferation, differentiation, and osteogenic genes of human bone marrow mesenchymal stem cells with 0.5, 1.0, and 3.0 μg/mL rhBMP2 doses in this study.MethodsIn vitro experimental study was designed to proliferation by a real‐time quantitative cell analysis system and the osteogenic differentiation by alkaline phosphatase (ALP) activity and osteogenic marker (Runx2, OPN, and OCN) gene expressions of human derived bone marrow mesenchymal stem cells (hBMMSCs). nHAp was produced by wet chemical process and characterized by Fourier transform infrared spectrophotometer, scanning electron microscopy, and energy‐dispersive x‐ray spectroscopy. PEG/PLA polymer was produced at a 51:49 molar ratio. 0.5, 1.0, and 3.0 μg/mL rhBMP2 and nHAp was combined with the polymers. hBMMSCs were characterized by multipotency assays and surface markers were assessed by flow cytometer. The hBMMSC‐rhBMP2 containing nHAp‐PEG/PLA composite interaction was evaluated by transmission electron microscopy. Proliferative effect was evaluated by real‐time proliferation analysis, and osteogenic capacity was evaluated by ALP activity assay and qPCR.ResultshBMMSC proliferation in the 0.5 μg/mL rhBMP2 + nHAp‐PEG/PLA and the 1.0 μg/mL rhBMP2 + nHAp‐PEG/PLA groups were higher compared to control. 1.0 μg/mL rhBMP2 + nHAp‐PEG/PLA and 3.0 μg/mL rhBMP2 + nHAp‐PEG/PLA containing composites induced ALP activity on days 3 and 10. 0.5 μg/mL rhBMP2 + nHAp‐PEG/PLA application stimulated Runx2 and OPN gene expressions.ConclusionrhBMP2 + nHAp‐PEG/PLA composites stimulate hBMMSC proliferation and differentiation. The nHAp‐PEG/PLA composite with low dose of rhBMP2 may enhance bone formation in future clinical PLSF applications.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

A pilot study: Nano‐hydroxyapatite‐PEG/PLA containing low dose rhBMP2 stimulates proliferation and osteogenic differentiation of human bone marrow derived mesenchymal stem cells

et al. 2023

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Collagen-based biomaterials for tissue engineering applications

Amirthalingam,

Hwang

2023

Natural Biopolymers in Drug Delivery and Tissue Engineering

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Peptide Hydrogel for Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 In Vitro

Wang,

Qi,

Zhang

et al. 2024

JFB

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This study aimed to investigate the impact of varying the formulation of a specific peptide hydrogel (PepGel) on the release kinetics of rhBMP-2 in vitro. Three PepGel formulations were assessed: (1) 50% v/v (peptides volume/total volume) PepGel, where synthetic peptides were mixed with crosslinking reagents and rhBMP-2 solution; (2) 67% v/v PepGel; (3) 80% v/v PepGel. Each sample was loaded with 12 µg of rhBMP-2 and incubated in PBS. Released rhBMP-2 was quantified by ELISA at 1 h, 6 h, and 1, 2, 4, 7, 10, 14, and 21 days. To explore how PepGel formulations influence rhBMP-2 release, the gel porosities, swelling ratios, and mechanical properties of the three PepGel formulations were quantitatively analyzed. The results showed that rhBMP-2 encapsulated with 50% v/v PepGel exhibited a sustained release over the 21-day experiment, while the 67% and 80% v/v PepGels demonstrated significantly lower rhBMP-2 release rates compared to the 50% formulation after day 7. Higher histological porosity of PepGel was significantly correlated with increased rhBMP-2 release rates. Conversely, the swelling ratio and elastic modulus of the 50% v/v PepGel were significantly lower than that of the 67% and 80% v/v formulations. In conclusion, this study indicates that varying the formulation of crosslinked PepGel can control rhBMP-2 release rates in vitro by modulating gel porosity, swelling ratio, and mechanical properties. Encapsulation with 50% v/v PepGel offers a sustained rhBMP-2 release pattern in vitro; if replicated in vivo, this could mitigate the adverse effects associated with burst release of rhBMP-2 in clinical applications.

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A BMP/Activin A Chimera Induces Posterolateral Spine Fusion in Nonhuman Primates at Lower Concentrations Than BMP-2

Cited by 3 publications

References 88 publications

A pilot study: Nano‐hydroxyapatite‐PEG/PLA containing low dose rhBMP2 stimulates proliferation and osteogenic differentiation of human bone marrow derived mesenchymal stem cells

A pilot study: Nano‐hydroxyapatite‐PEG/PLA containing low dose rhBMP2 stimulates proliferation and osteogenic differentiation of human bone marrow derived mesenchymal stem cells

Collagen-based biomaterials for tissue engineering applications

Peptide Hydrogel for Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 In Vitro

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