BMP2 related oligopeptide as a potential therapeutic agent to accelerate bone formation and bone defect repairing in osteoporotic fracture: Effect on rat cranial bone defects repair

Abstract Bone defects that cannot be healed completely are termed critical-sized defects and can be used to test bone grafts for medicine, dentistry, and periodontology. The aim of the present study was to detect the effects of a xenograft (Unilab Surgibone) on bone building in experimentally created parietal bone defects in rats. Standardized parietal bone defects were created in 16 rats, and each defect had a circular morphology 6 mm in diameter. The right defect sites were filled with porous particle material, and the left site was used as control. After the 3rd, 6th, and 12th months, rats were killed and tissue samples obtained from the related site of the cranium. Subsequently, histological sections were taken and stained with different stains for evaluation under light microscope. The rate of bone formation was assessed using a semiquantitative method. These results showed that dense collagenous tissue was observed in the control area during the third month, whereas xenograft particles were surrounded by a fibrous tissue layer at the implantation site. Osteoclast-like cells were also observed. There was also no significant bone repair at other observation periods. It can be concluded that the material used had no evidence of resorption and does not enhance bone formation. However, it seems biocompatible, osteoconductive, and could be used in a limited manner as a material for filling osseous defects in clinical practice.

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Association of marine Collagen/Biosilicate composites and photobiomodulation in the process of bone healing using an experimental model of calvarial defect

Research Society and Development ◽

10.33448/rsd-v10i8.16498 ◽

2021 ◽

Vol 10 (8) ◽

pp. e8610816498

Author(s):

Giovanna Caroline Aparecida do Vale ◽

Kelly Rossetti Fernandes ◽

Julia Risso Parisi ◽

Alan de França Santana ◽

Matheus de Almeida Cruz ◽

...

Keyword(s):

Bone Formation ◽

Experimental Model ◽

Histological Analysis ◽

Bone Defects ◽

Bone Volume ◽

Cranial Bone ◽

Calvarial Defect ◽

Regenerative Capacity ◽

Biological Performance ◽

Over Time

The study comparing the bone regenerative capacity in an experimental model of cranial bone defects in rats, into 3 groups: G1: bone defects irradiated with photobiomodulation; G2: Biosilicate + photobiomodulation and G3: Biosilicate and Spongin + photobiomodulation. Histocompatibility and bone responses were performed after 15 and 45 days of implantation. Histological analysis demonstrated that photobiomodulation irradiated animals presented an increased amount of newly formed over time. Histomorphometry showed higher values for bone volume for G3 and G1, higher values for osteoid volume and number of osteoblasts observed for G3 compared to G2. TGF-β immunolabelling was higher for G2. The values found for VEGF were higher for biosilicate (with or without spongin) 15 days of implantation with an increased difference being observed for G1, 45 days after surgery. In conclusion, the stimulus provided by photobiomodulation associated to the biomimetic composite increased bone formation in the cranial bone defect in rats. Consequently, these data highlight the potential of the introduction of spongin into biosilicate and irradiated with photobiomodulation to improve the biological performance for bone regeneration applications.

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

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.7385 ◽

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.

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ONO-1301 loaded nanocomposite scaffolds modulate cAMP mediated signaling and induce new bone formation in critical sized bone defect

Biomaterials Science ◽

10.1039/c9bm01352k ◽

2020 ◽

Vol 8 (3) ◽

pp. 884-896 ◽

Cited By ~ 1

Author(s):

Shruthy Kuttappan ◽

Jun-ichiro Jo ◽

Deepthy Menon ◽

Takuya Ishimoto ◽

Takayoshi Nakano ◽

...

Keyword(s):

Growth Factors ◽

Bone Formation ◽

Bone Defect ◽

Small Molecule ◽

Bone Defects ◽

New Bone Formation ◽

Osteoinductive Potential ◽

Nanocomposite Scaffolds

Small molecule ONO-1301 displayed chemotactic and osteoinductive potential in critical sized bone defects and suggested as a replacement for high cost and unstable protein based growth factors.

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

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-01977-z ◽

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.

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Synthetic Scaffold/Dental Pulp Stem Cell (DPSC) Tissue Engineering Constructs for Bone Defect Treatment: An Animal Studies Literature Review

International Journal of Molecular Sciences ◽

10.3390/ijms21249765 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9765

Author(s):

Felice Lorusso ◽

Francesco Inchingolo ◽

Gianna Dipalma ◽

Francesca Postiglione ◽

Stefania Fulle ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Bone Defect ◽

Dental Pulp ◽

Animal Studies ◽

Meta Analysis ◽

Bone Defects ◽

New Bone Formation ◽

Synthetic Scaffold ◽

Bone Defect Treatment

Background: Recently a greater interest in tissue engineering for the treatment of large bone defect has been reported. The aim of the present systematic review and meta-analysis was to investigate the effectiveness of dental pulp stem cells and synthetic block complexes for bone defect treatment in preclinical in vivo articles. Methods: The electronic database and manual search was conducted on Pubmed, Scopus, and EMBASE. The papers identified were submitted for risk-of-bias assessment and classified according to new bone formation, bone graft characteristics, dental pulp stem cells (DPSCs) culture passages and amount of experimental data. The meta-analysis assessment was conducted to assess new bone formation in test sites with DPSCs/synthetic blocks vs. synthetic block alone. Results: The database search identified a total of 348 papers. After the initial screening, 30 studies were included, according to the different animal models: 19 papers on rats, 3 articles on rabbits, 2 manuscripts on sheep and 4 papers on swine. The meta-analysis evaluation showed a significantly increase in new bone formation in favor of DPSCs/synthetic scaffold complexes, if compared to the control at 4 weeks (Mean Diff: 17.09%, 95% CI: 15.16–18.91%, p < 0.01) and at 8 weeks (Mean Diff: 14.86%, 95% CI: 1.82–27.91%, p < 0.01) in rats calvaria bone defects. Conclusion: The synthetic scaffolds in association of DPSCs used for the treatment of bone defects showed encouraging results of early new bone formation in preclinical animal studies and could represent a useful resource for regenerative bone augmentation procedures

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Titanium Mesh Implants - Alternative for Cranial Bone Defects

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.752.105 ◽

2017 ◽

Vol 752 ◽

pp. 105-110

Author(s):

Dan Mihai Teleanu ◽

Alexandru Cristescu ◽

Stefan Bogaciu ◽

Raluca Ioana Teleanu ◽

Alexandru Vlad Ciurea

Keyword(s):

Bone Defect ◽

Operating Time ◽

Functional Results ◽

Bone Defects ◽

Cranial Bone ◽

Titanium Mesh ◽

Calvarial Bone ◽

The Aesthetic ◽

Reliable Solution ◽

Mesh Implant

Calvarial bone defects are due to cranial bone removal at the end of the surgery (decompressive craniectomy), either because of bone involvement of the tumor or as a method to relieve intracranial pressure caused by important cerebral edema secondary to large tumors or traumas. With the progress of biomedical technology, new materials are available for use by surgeons. The titanium mesh implant is a plating platform with a matrix design and MRI compatibility that can be easily shaped, cut, and bent by the surgeon according to the bone defect. It is locked in place by several screws tapped into the bone. Although may different type of materials are currently available there is no consensus for the best method to be used. The aim of this study was to report our experience with titanium mesh implants for cranial repair and reconstruction of bone anatomy.Twenty four patients with decompressive craniectomies that required reconstruction of the calvarial bone defect for which a titanium mesh cranioplasty was used, operated in our Neurosurgery Department between January 2013 and April 2016 where included in this retrospective study. Of the 24 patients, only one had a localized infection complication for which the patient was re-operated and the implant removed with no other complications. No other neurological, infectious and functional complications were observed during or after surgery. All other patients had excellent anatomic and functional results with a positive feedback for the aesthetic aspects of the implant. The use of these bio-compatible materials is a viable, safe and reliable solution for the management of cranial bone defects offering the surgeon a large array of options for the benefit of the patient. It has a proven cost-effectiveness when compared to other customized prosthetics with the same outcomes. The MRI compatibility was proven very useful, especially for neoplasm patients who required frequent cranial imaging follow-ups, and reduced operating time was particularly beneficial to elderly patients.

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Effect of topical Insulin administration on bone defect healing in diabetic rats

Brazilian Dental Science ◽

10.14295/bds.2020.v23i2.1914 ◽

2020 ◽

Vol 23 (2) ◽

Author(s):

Hany Mahmoud Mahmoud ◽

Hanyabd-elhamed Sheriff ◽

Abd-elnasserabd-Elmoala Ismael ◽

Alaaabd-alla Zaki

Keyword(s):

Bone Formation ◽

Bone Defect ◽

Healing Process ◽

Bone Defects ◽

Diabetic Control ◽

Diabetic Rats ◽

Control Group ◽

Group I ◽

Group Ii ◽

Experimental Group

Objective: insulin has been reported to possess anabolic effect on bone. Topical application of insulin in bone defects in diabetic rats has not been investigated. The objective of this study was to evaluate histologically the effect of topical administration of insulin for the restoration of tibial bone defects in diabetic rats. Materials and Methods: Sixteen adult male albino diabetic rats were grouped into two equal groups, group I (diabetic control) which had not received any graft, group II (experimental) which was diabetic and had received topical insulin loaded on PVP (Polyvinylpyrrolidone). Specimens were harvested on days seven and twenty eight days after surgical procedures, prepared and examined histologically by H&E (haematoxylin and eosin) stain, there were wide histological differences between the groups of this study along the different intervals of the study.Results:The histological results demonstrated that there was obvious retardation in resolving the inflammatory phase, organization of the blood clot and bone formation in the diabetic control group I than the experimental group II along the different intervals of this study. Moreover, there was great acceleration in granulation tissue formation, organization and bone formation in experimental group II which received the insulin PVP. Discussion: The enhancement in bone healing process was due to the effect of insulin which accelerates the bone regeneration by means of inflammation resolve, angiogenesis, proliferation and successive differentiation of mesenchymal cells. Conclusion: Topical applications of insulin in bone defects enhance new bone formation in diabetic rats.KEYWORDSInsulin; Bone defect; Tibia; Diabetes; Rats.

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The combinatory effect of sinusoidal electromagnetic field and VEGF promotes osteogenesis and angiogenesis of mesenchymal stem cell-laden PCL/HA implants in a rat subcritical cranial defect

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1464-x ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Jingyuan Chen ◽

Chang Tu ◽

Xiangyu Tang ◽

Hao Li ◽

Jiyuan Yan ◽

...

Keyword(s):

Tissue Engineering ◽

Electromagnetic Field ◽

Bone Formation ◽

Bone Regeneration ◽

Bone Defect ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Bone Defects ◽

Histological Evaluation ◽

Cranial Defect

Abstract Background Restoration of massive bone defects remains a huge challenge for orthopedic surgeons. Insufficient vascularization and slow bone regeneration limited the application of tissue engineering in bone defect. The effect of electromagnetic field (EMF) on bone defect has been reported for many years. However, sinusoidal EMF (SEMF) combined with tissue engineering in bone regeneration remains poorly investigated. Methods In the present study, we investigated the effect of SEMF and vascular endothelial growth factor (VEGF) on osteogenic and vasculogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, pretreated rBMSC- laden polycaprolactone-hydroxyapatite (PCL/HA) scaffold was constructed and implanted into the subcritical cranial defect of rats. The bone formation and vascularization were evaluated 4 and 12 weeks after implantation. Results It was shown that SEMF and VEGF could enhance the protein and mRNA expression levels of osteoblast- and endothelial cell-related markers, respectively. The combinatory effect of SEMF and VEGF slightly promoted the angiogenic differentiation of rBMSCs. The proteins of Wnt1, low-density lipoprotein receptor-related protein 6 (LRP-6), and β-catenin increased in all inducted groups, especially in SEMF + VEGF group. The results indicated that Wnt/β-catenin pathway might participate in the osteogenic and angiogenic differentiation of rBMSCs. Histological evaluation and reconstructed 3D graphs revealed that tissue-engineered constructs significantly promoted the new bone formation and angiogenesis compared to other groups. Conclusion The combinatory effect of SEMF and VEGF raised an efficient approach to enhance the osteogenesis and vascularization of tissue-engineered constructs, which provided a useful guide for regeneration of bone defects.

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