scholarly journals Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration

2020 ◽  
Vol 6 (1) ◽  
pp. eaay1240 ◽  
Author(s):  
Marian H. Hettiaratchi ◽  
Laxminarayanan Krishnan ◽  
Tel Rouse ◽  
Catherine Chou ◽  
Todd C. McDevitt ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Bone Morphogenetic Protein ◽  
Spatial Localization ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Large Bone ◽  
Large Bone Defects

Supraphysiologic doses of bone morphogenetic protein-2 (BMP-2) are used clinically to promote bone formation in fracture nonunions, large bone defects, and spinal fusion. However, abnormal bone formation (i.e., heterotopic ossification) caused by rapid BMP-2 release from conventional collagen sponge scaffolds is a serious complication. We leveraged the strong affinity interactions between heparin microparticles (HMPs) and BMP-2 to improve protein delivery to bone defects. We first developed a computational model to investigate BMP-2–HMP interactions and demonstrated improved in vivo BMP-2 retention using HMPs. We then evaluated BMP-2–loaded HMPs as a treatment strategy for healing critically sized femoral defects in a rat model that displays heterotopic ossification with clinical BMP-2 doses (0.12 mg/kg body weight). HMPs increased BMP-2 retention in vivo, improving spatial localization of bone formation in large bone defects and reducing heterotopic ossification. Thus, HMPs provide a promising opportunity to improve the safety profile of scaffold-based BMP-2 delivery.

scholarly journals Poly(POG)n loaded with recombinant human bone morphogenetic protein-2 accelerates new bone formation in a critical-sized bone defect mouse model

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ryo Tazawa ◽  
Kentaro Uchida ◽  
Hiroaki Minehara ◽  
Terumasa Matsuura ◽  
Tadashi Kawamura ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defect ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Morphogenetic Protein ◽  
Large Bone ◽  
Large Bone Defects

Abstract Background Delivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects. However, the administration of bovine proteins to humans is associated with the risk of zoonotic complications. We therefore examined the effect of combining BMP-2 with collagen-like peptides, poly(POG)n, in a critical-sized bone defect mouse model. Methods A 2-mm critical-sized bone defect was created in the femur of 9-week-old male C57/BL6J mice. Mice were randomly allocated into one of four treatment groups (n = 6 each): control (no treatment), poly(POG)n only, 0.2 μg, or 2.0 μg BMP-2 with poly(POG)n. New bone formation was monitored using soft X-ray radiographs, and bone formation at the bone defect site was examined using micro-computed tomography and histological examination at 4 weeks after surgery. Results Administration of 2.0 μg of BMP-2 with poly(POG)n promoted new bone formation and resulted in greater bone volume and bone mineral content than that observed in the control group and successfully achieved consolidation. In contrast, bone formation in all other groups was scarce. Conclusions Our findings suggest the potential of BMP-2 with poly(POG)n as a material, free from animal-derived collagen, for the treatment of large bone defects.

Bone Morphogenetic Protein 2 and Retinoic Acid Accelerate in Vivo Bone Formation, Osteoclast Recruitment, and Bone Turnover

2005 ◽  
Vol 11 (3-4) ◽  
pp. 645-658 ◽  
Author(s):  
Catherine M. Cowan ◽  
Oliver O. Aalami ◽  
Yun-Ying Shi ◽  
Yu-Fen Chou ◽  
Carina Mari ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
In Vivo Bone Formation

scholarly journals Effect of Stromal Vascular Fraction on Fracture Healing with Bone Defects by Examination of Bone Morphogenetic Protein-2 Biomarkers in Murine Model

2021 ◽  
Vol 9 (A) ◽  
pp. 1132-1136
Author(s):  
Respati S. Dradjat ◽  
Panji Sananta ◽  
Rizqi Daniar Rosandi ◽  
Lasa Dhakka Siahaan
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defect ◽  
Murine Model ◽  
Healing Process ◽  
Stromal Vascular Fraction ◽  
Bone Defects ◽  
The Body ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

BACKGROUND: Fractures and segmental bone defects are a significant cause of morbidity and a source of a high economic burden in healthcare. A severe bone defect (3 mm in murine model) is a devastating condition, which the bone cannot heal naturally despite surgical stabilization and usually requires further surgical intervention. The stromal vascular fraction (SVF) contains a heterogeneous collection of cells and several components, primarily: MSCs, HSCs, Treg cells, pericytic cells, AST cells, extracellular matrix, and complex microvascular beds (fibroblasts, white blood cells, dendritic cells, and intra-adventitial smooth muscular-like cells). Bone morphogenetic protein (BMP) is widely known for their important role in bone formation during mammalian development and confers a multifunctional role in the body, which has potential for therapeutic use. Studies have shown that BMPs play a role in the healing of large size bone defects. AIM: In this study, researchers aim to determine the effect of administering SVF from adipose tissue on the healing process of bone defects assessed based on the level biomarker of BMP-2. MATERIALS AND METHODS: This was an animal study involving 12 Wistar strain Rattus norvegivus. They were divided into three groups: Negative group (normal rats), positive group (rats with bone defect without SVF application), and SVF group (rats with bone defect with SVF application). After 30 days, the rats were sacrificed; the biomarkers that were evaluated are BMP-2. This biomarker was quantified using ELISA. RESULTS: BMP-2 biomarker expressions were higher in the SVF application group than in the group without SVF. All comparisons of the SVF group and positive control group showed significant differences (p = 0.026). CONCLUSION: SVF application could aid the healing process in a murine model with bone defect marked by the increased level of BMP-2 as a bone formation marker.

scholarly journals Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo

2007 ◽  
Vol 42 (3) ◽  
pp. 267-273 ◽  
Author(s):  
J. D. Bradley ◽  
D. G. Cleverly ◽  
A. M. Burns ◽  
N. B. Helm ◽  
M. J. Schmid ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Cyclooxygenase 2 ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

scholarly journals Umbilical Cord Mesenchymal Stem Cell-Derived Nanovesicles Potentiate the Bone-Formation Efficacy of Bone Morphogenetic Protein 2

2020 ◽  
Vol 21 (17) ◽  
pp. 6425
Author(s):  
Songhyun Lim ◽  
Hao-Zhen Lyu ◽  
Ju-Ro Lee ◽  
Shi Huan Han ◽  
Jae Hyup Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Umbilical Cord ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Calvarial Defects ◽  
In Vivo Bone Formation

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.

Bone morphogenetic protein gene therapy for the induction of spinal arthrodesis

1998 ◽  
Vol 4 (2) ◽  
pp. E14 ◽  
Author(s):  
Tord D. Alden ◽  
Gerald R. Hankins ◽  
Elisa J. Beres ◽  
David F. Kallmes ◽  
Gregory A. Helm
Keyword(s):  
Gene Therapy ◽  
Bone Formation ◽  
Spinal Fusion ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Lumbosacral Spine ◽  
Ct Reconstruction ◽  
Morphogenetic Protein ◽  
Adenoviral Construct

Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion. Twelve athymic nude rats were used in this study. Recombinant, replication-defective type-5 adenovirus with a universal promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with a universal promoter and ß-galactosidase (ß-gal) gene (Ad-ß-gal) was used as a control. Seven and one-half microliters of virus was injected percutaneously and paraspinally at the lumbosacral junction in three groups (four animals each): 1) Ad-BMP-2 bilaterally, 2) Ad-BMP-2 on the right, Ad-ß-gal on the left, and 3) Ad-ß-gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spine were obtained at 3, 5, and 12 weeks. At 12 weeks, the animals were killed for histological inspection. Ectopic bone formation was seen both on three-dimensional CT reconstruction and histologically in all rats at sites treated with Ad-BMP-2. Histological analysis revealed bone at different stages of maturity adjacent to the spinous processes, laminae, and transverse processes. This study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that gene therapy may be useful for spinal fusion in the future.

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