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 ◽  
...  

Treating bone defects is still a challenge in clinical practice.

2021 ◽  
Vol 9 (A) ◽  
pp. 1132-1136
Author(s):  
Respati S. Dradjat ◽  
Panji Sananta ◽  
Rizqi Daniar Rosandi ◽  
Lasa Dhakka Siahaan

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.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ryo Tazawa ◽  
Kentaro Uchida ◽  
Hiroaki Minehara ◽  
Terumasa Matsuura ◽  
Tadashi Kawamura ◽  
...  

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.


2020 ◽  
Vol 6 (1) ◽  
pp. eaay1240 ◽  
Author(s):  
Marian H. Hettiaratchi ◽  
Laxminarayanan Krishnan ◽  
Tel Rouse ◽  
Catherine Chou ◽  
Todd C. McDevitt ◽  
...  

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.


2014 ◽  
Vol 10 (10) ◽  
pp. 4390-4399 ◽  
Author(s):  
Lauren B. Priddy ◽  
Ovijit Chaudhuri ◽  
Hazel Y. Stevens ◽  
Laxminarayanan Krishnan ◽  
Brent A. Uhrig ◽  
...  

2002 ◽  
Vol 39 (4) ◽  
pp. 439-448 ◽  
Author(s):  
Tatsuo Kawamoto ◽  
Nobuyoshi Motohashi ◽  
Atsushi Kitamura ◽  
Yoshiyuki Baba ◽  
Koichiro Takahashi ◽  
...  

Objective The purpose of this preliminary study was to examine experimental tooth movement into newly generated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2). Method After extraction of the maxillary first premolars, bone defects were surgically created in eight adult beagle dogs using a 5-mm-diameter trepan bar. According to which material was grafted into the bone defects, animals were divided into the following four groups: (1) the rhBMP-2 group in which rhBMP-2 with a poly [D,L-(lactide-co-glycolide)]/gelatin sponge complex was implanted; (2) the spongiosa group in which spongiosa from the tibia was grafted; (3) the nongrafted group in which no material was embedded; and (4) the control group in which only tooth extraction was performed. The osteoinductive activity of rhBMP-2 and tooth movement into the newly generated bone were examined by histological and morphometric comparisons of each group. Results Considerable new bone formation was observed at the grafted site both in the rhBMP-2 and in the spongiosa groups. The area of generated bone in the rhBMP-2 group was significantly greater than that in the spongiosa group. Newly generated bone, in both the rhBMP-2 and spongisosa groups, showed a similar histological response to orthodontic force as in normal alveolar bone in the control group. However, root resorption occurred on the pressure side in the rhBMP-2 group. Conclusion These results indicated that rhBMP-2 might constitute an alternative material to autogeneous bone grafting for alveolar cleft defects. Further studies regarding tooth movement into generated bone induced by rhBMP-2 are suggested.


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