Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration

Kempen, Diederik H.R.; Lu, Lichun; Heijink, Andras; Hefferan, Theresa E.; Creemers, Laura B.; Maran, Avudaiappan; Yaszemski, Michael J.; Dhert, Wouter J.A.

doi:10.1016/j.biomaterials.2009.01.031

Cited by 543 publications

(509 citation statements)

References 57 publications

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“…The ability of BMPs to increase the levels of VEGFA mRNA in a concentration and time-dependent fashion has been shown [12,23,51]. Additional synergy between diffusible osteogenic morphogens and proangiogenic factors has been shown to enhance the rate of ectopic bone growth through modulation of angiogenesis, recruitment and induction of local progenitor cells, and enhancement of cell survival [28,42]. Increased expression of BMP-2 and VEGFA transcripts in wounds that had ectopic bone develop further emphasizes their importance in the pathogenesis of HO.…”

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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Background Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. Question/purposes The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. Methods Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. Conclusions Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds.

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Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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“…Combined use of VEGF and BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36] showed synergistic effects in osteogenesis. It has been shown that combined use of VEGF with one of the most potent BMPs, BMP-6 [23,26], enhances osteogenesis and angiogenesis of mouse bone marrow stem cells in vitro and in vivo [8], however, the effectiveness of this therapy for ON has not been determined.…”

Section: Questions/hypothesesmentioning

confidence: 95%

“…Stem cell-mediated bone regeneration augmented with combined use of VEGF and BMPs has been reported but only for BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36]. It has been shown that VEGF enhances BMP-6-induced osteogenesis of mouse stem cells in vitro and in vivo, however, the effectiveness of this therapy for ON has not been determined [8].…”

Section: Next Stepsmentioning

confidence: 99%

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

Cui

Botchwey

2011

Clinical Orthopaedics &Amp; Related Research

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“…VEGF dosage must be tightly controlled as excessive amounts of this GF can inhibit osteogenesis and cause severe leakage and hypotension. 167 Combined results of Kempen et al 165 and Patel et al 45 suggest that the enhanced effect of VEGF and BMP-2 combination is both time-and location-dependent, which is not surprising due to the complexity of the pathways involved in bone healing. While Kempen et al 165 displayed an extremely high VEGF burst release of around 80%, De la Riva et al 166 reduced this stage to 20% and obtained considerable enhanced bone formation in the dual-release system they proposed (combination of VEGF and PDGF).…”

Section: From Single To Multiple Bioactive Factor Delivery For Skeletmentioning

confidence: 98%

“…167 Combined results of Kempen et al 165 and Patel et al 45 suggest that the enhanced effect of VEGF and BMP-2 combination is both time-and location-dependent, which is not surprising due to the complexity of the pathways involved in bone healing. While Kempen et al 165 displayed an extremely high VEGF burst release of around 80%, De la Riva et al 166 reduced this stage to 20% and obtained considerable enhanced bone formation in the dual-release system they proposed (combination of VEGF and PDGF). Shah et al 167 showed that dual release of VEGF and BMP-2 from polyelectrolyte multilayers induced a more complete bone architecture than the single dose of BMP-2, promoting a greater initial concurrent vascularization process and consequent introduction of more cells in the interior on the scaffolds.…”

Section: From Single To Multiple Bioactive Factor Delivery For Skeletmentioning

confidence: 98%

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

Santo

Gomes²,

Mano³

et al. 2013

Tissue Engineering Part B: Reviews

105

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The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.

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Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration

Cited by 543 publications

References 57 publications

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

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