Bone Morphogenetic Protein‐2 and Vascular Endothelial Growth Factor in Bone Tissue Regeneration: New Insight and Perspectives

Aryal, Rajendra; Chen, Xiaopeng; Fang, Cheng; Hu, Yongcheng

doi:10.1111/os.12112

Cited by 38 publications

(32 citation statements)

References 95 publications

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“…115 Recent evidence suggests that not only does VEGF produce angiogenesis but there is also cross-talk between VEGF and the BMP signaling pathway that plays a role in osteoblastic differentiation of MSCs. 116 Unlike BMP-2, the use of VEGF alone in bone fractures is not sufficient enough to lead to complete healing; 117 however, when combined with BMP-2, VEGF increases the rate of complete union healing in defects in a synergistic manner in rat models with critical size defects. 117 It must be noted, however, that although combination treatment with BMP-2 and VEGF possesses superior efficacy of bone formation, coimplantation and corresponding angiogenesis may result in aberrant migration of BMP-2 to unwanted areas and potentiate higher rates of ectopic bone formation.…”

Section: Addition Of Vascular Endothelial Growth Factormentioning

confidence: 99%

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

James

LaChaud

Shen

et al. 2016

Tissue Engineering Part B: Reviews

823

769

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Bone morphogenetic protein-2 (BMP-2) is currently the only Food and Drug Administration (FDA)-approved osteoinductive growth factor used as a bone graft substitute. However, with increasing clinical use of BMP-2, a growing and well-documented side effect profile has emerged. This includes postoperative inflammation and associated adverse effects, ectopic bone formation, osteoclast-mediated bone resorption, and inappropriate adipogenesis. Several large-scale studies have confirmed the relative frequency of adverse events associated with the clinical use of BMP-2, including life-threatening cervical spine swelling. In fact, the FDA has issued a warning of the potential life-threatening complications of BMP-2. This review summarizes the known adverse effects of BMP-2, including controversial areas such as tumorigenesis. Next, select animal models that replicate BMP-2's adverse clinical effects are discussed. Finally, potential molecules to mitigate the adverse effects of BMP-2 are reviewed. In summary, BMP-2 is a potent osteoinductive cytokine that has indeed revolutionized the bone graft substitute market; however, it simultaneously has accrued a worrisome side effect profile. Better understanding of these adverse effects among both translational scientists and clinicians will help determine the most appropriate and safe use of BMP-2 in the clinical setting.

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Section: Addition Of Vascular Endothelial Growth Factormentioning

confidence: 99%

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

James

LaChaud

Shen

et al. 2016

Tissue Engineering Part B: Reviews

823

769

View full text Add to dashboard Cite

show abstract

“…Due to the complexity of the in vivo environment and the short half-lives of growth factors, the natural spatiotemporal release profile of growth factors cannot be easily simulated by exogenous delivery. Often, supraphysiological doses are administered with possible adverse effects 5,7) . Furthermore, recombinant protein costs represent a significant financial burden for the patient 8) .…”

Section: Introductionmentioning

confidence: 99%

Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells

Rombouts

Jeanneau

Camilleri

et al. 2016

Dental Materials Journal

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Adequate revascularization is a prerequisite for successful healing of periodontal bone defects. This study characterized three different xenogeneic bone grafting materials: Gen-Os of equine and porcine origins, and anorganic Bio-Oss. We also investigated their angiogenic potential. All materials were composed of poorly crystalline calcium oxide phosphate, with Bio-Oss exhibiting a carbonated phase and larger particle size and both Gen-Os showing the presence of collagen. Both Gen-Os materials significantly enhanced vascular endothelial growth factor (VEGF) secretion by PDL cells. A significant increase in endothelial cell proliferation was observed in cultures with both Gen-Os conditioned media, but not with that of Bio-Oss. Finally, angiogenesis was stimulated by both Gen-Os conditioned media as demonstrated by an increased formation of capillary-like structures. Taken together, these findings indicate an enhanced angiogenic potential of both Gen-Os bone grafting materials when applied on PDL cells, most likely by increasing VEGF production.

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“…rhVEGF is an angiogenic factor critical for both intramembranous and endochondral bone formation. Dual application of rhBMP‐2 and rhVEGF has been regarded as one of the most efficient system for effective vascularized bone formation 5, 19, 20. However, traditional delivery techniques have exhibited an unfavorable therapeutic effect.…”

Section: Resultsmentioning

confidence: 99%

“…The engineering techniques that mimic the critical aspects of natural healing and growth cascade, is widely utilized to artificially augment the proliferation and differentiation of the recruited or implanted cells via the integration of growth factors and cytokines that providing suitable biochemical and physicochemical factors for tissue regeneration. Therefore, combining the design of a 3D biomimetic fluid perfused scaffold and an effective growth factor delivery method is regarded as a highly promising technique for vascularized bone regeneration research, especially for eventual clinical applications 3, 4, 5…”

Section: Introductionmentioning

confidence: 99%

Biologically Inspired Smart Release System Based on 3D Bioprinted Perfused Scaffold for Vascularized Tissue Regeneration

et al. 2016

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A critical challenge to the development of large‐scale artificial tissue grafts for defect reconstruction is vascularization of the tissue construct. As an emerging tissue/organ manufacturing technique, 3D bioprinting offers great precision in controlling the internal architecture of a scaffold with preferable mechanical strength and printing complicated microstructures comparable to native tissue. However, current bioprinting techniques still exhibit difficulty in achieving biomimetic nano resolution and cooperating with bioactive spatiotemporal signals. In this study, a comprehensive design of engineered vascularized bone construct is presented for the first time by integrating biomimetic 3D bioprinted fluid perfused microstructure with biologically inspired smart release nanocoating, which is regarded as an aspiring concept combining engineering, biological, and material science. In this biologically inspired design, angiogenesis and osteogenesis are successively induced through a matrix metalloprotease 2 regulative mechanism by delivering dual growth factors with sequential release in spatiotemporal coordination. Availability of this system is evaluated in dynamic culture condition, which is similar to fluid surrounding in vivo, as an alternative animal model study. Results, particularly from co‐cultured dynamically samples demonstrate excellent bioactivity and vascularized bone forming potential of nanocoating modified 3D bioprinted scaffolds for human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells.

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Bone Morphogenetic Protein‐2 and Vascular Endothelial Growth Factor in Bone Tissue Regeneration: New Insight and Perspectives

Cited by 38 publications

References 95 publications

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells

Biologically Inspired Smart Release System Based on 3D Bioprinted Perfused Scaffold for Vascularized Tissue Regeneration

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