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 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.

scholarly journals ID: 1058 Effective bone formation through BMP-2-immobilized highly porous GBR membrane

2017 ◽  
Vol 4 (S) ◽  
pp. 139
Author(s):  
Min Ji Kim ◽  
Jin Hyun Park ◽  
Ho Yong Kim ◽  
June Ho Byun ◽  
Jin Ho Lee ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Active Sites ◽  
Healing Process ◽  
The Body ◽  
Bioactive Molecules ◽  
Bone Morphogenetic Protein 2 ◽  
Gbr Membrane

Sound healing of large bone defects is critical challenges in most of clinical fields. In general healing process of bone regeneration, the rapid infiltration of connective tissue, whereas relatively slow bone regeneration in bone defect leads to the incomplete bone formation. To solve this drawback, guide bone regeneration (GBR) membrane which could prevent rapid infiltration of connective tissue into bone defect, thus GBR membrane is feasible for compact bone regeneration in clinical fields. In recent, the most researchers believed that bioactive molecules-grafted GBR membranes may enhance the bone regeneration. To allow graft of bioactive molecules from porous membrane, chemically modified scaffolds are commonly used. This modification leads to sufficient interaction with active sites of bioactive molecules to stable the immobilization of bioactive molecules in the body. However it is hard to apply to clinical applications because of the toxicity of chemical residue used for the modification. In this study, we developed a GBR membrane with leaf-stacked structure which can allow sustained release of bone morphogenetic protein-2 (BMP-2) without any additional modification. The morphology, mechanical property, BMP-2 release profile, osteogenic differentiation of human periosteum-derived cells, and new bone formation efficiency of the BMP-2-loaded GBR membrane compared with commercial product were investigated.

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.

Acceleration of bone formation using in situ-formed hyaluronan-hydrogel containing bone morphogenetic protein-2 in a mouse critical size bone defect model

2021 ◽  
pp. 1-9
Author(s):  
Shintaro Shoji ◽  
Kentaro Uchida ◽  
Ryo Tazawa ◽  
Wataru Saito ◽  
Akiyoshi Kuroda ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defect ◽  
Bone Repair ◽  
Critical Size ◽  
Bone Morphogenetic Protein 2 ◽  
Micro Computed Tomography ◽  
Defect Model ◽  
Morphogenetic Protein

BACKGROUND: An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHGs). IFHGs may also be ideal carrier materials for bone repair, although their ability to carry bone morphogenetic protein-2 (BMP2) has yet to be examined. OBJECTIVE: We examined the effectiveness of an IFHG made of hyaluronan (IFHG-HA) containing BMP2 for promoting bone formation in a mouse critical size bone defect model. METHODS: C57/BL6J mice received a 2-mm femoral critical-sized bone defect before being randomly assigned to one of the following treatment groups (n = 6): control (no treatment), IFHG-HA only, PBS with BMP2, and IFHG-HA with BMP2. X-ray radiographs were utilized to track new bone formation, and micro-computed tomography and histological examination were performed on new bone formed at the bone defect site two weeks after surgery. RESULTS: Mice treated with PBS with BMP2 and IFHG-HA with BMP2 had greater bone volume (BV) and bone mineral content (BMC) than those receiving control, and successfully achieved consolidation. Mice treated with IFHG-HA with BMP2 had significantly higher BV and BMC than those treated with PBS with BMP2. CONCLUSIONS: IFHG-HA may be an effective carrier for BMP2 to enable delivery for bone defect repair.

Effective delivery of bone morphogenetic protein 2 gene using chitosan–polyethylenimine nanoparticle to promote bone formation

RSC Advances ◽  
2016 ◽  
Vol 6 (41) ◽  
pp. 34081-34089 ◽  
Author(s):  
Liang Zhao ◽  
Kai Zhang ◽  
Wenhuan Bu ◽  
Xiaowei Xu ◽  
Han Jin ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Effective Delivery

Treating bone defects is still a challenge in clinical practice.

Nano-Hydroxyapatite Scaffold Based on Recombinant Human Bone Morphogenetic Protein 2 and Its Application in Bone Defect Repair

2021 ◽  
Vol 17 (7) ◽  
pp. 1330-1338
Author(s):  
Shibai Zhu ◽  
Xiaotian Zhang ◽  
Xi Chen ◽  
Yiou Wang ◽  
Shanni Li ◽  
...  
Keyword(s):  
Bone Defect ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Artificial Bone ◽  
Bone Defect Repair ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Defect Repair ◽  
Hydroxyapatite Scaffold ◽  
Recombinant Human Bone

The best way in which to prepare scaffolds with good biological properties is an urgent problem in the field of tissue engineering. In this paper we discuss the preparation of nano-hydroxyapatite scaffold of recombinant human bone morphogenetic protein-2 (rhBMP-2) and its application in bone defect repair. rhBMP-2 reagent was dissolved in 1 mol/L sodium dihydrogen phosphate solution, and the rhBMP-2 solution was added to the nano-hydroxyapatite artificial bone with a 100 μL glass micro dropper at the rate of 10 drops/min to obtain Nano-HA/rhBMP-2 composite artificial bone. In in vivo experiments, rabbits were fixed on an operating table, a 2 cm longitudinal incision was made in the middle part of the radial forearm, and the radius was cut with a wire saw and periosteum, 2.5 cm away from the distal radius. After washing the wound with normal saline, Adv-hBMP-2/MC3T3-E1 nano-HA composite artificial bone, MC3T3-E1 nan-HA composite artificial bone, or Nano-HA artificial bone were implanted in different groups. The artificial bone scaffold prepared in this study has a stronger ability to repair bone defects than the alternatives, and is a promising prospect for the clinical treatment of bone defects.

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