Augmenting Neovascularization Accelerates Distraction Osteogenesis

Davidson, Edward H.; Sultan, Steven M.; Butala, Parag; Tutela, John Paul; Cañizares, Orlando; Wagner, I. Janelle; Knobel, Denis; Saadeh, Pierre B.

doi:10.1097/prs.0b013e31821e6e2e

Cited by 17 publications

(12 citation statements)

References 28 publications

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“…AMD3100 was FDA-approved in 2008 for the mobilization of hematopoetic stem cells [27], [30]–[32]. Specifically, AMD3100 mobilizes hematopoetic stem cells by competitively binding to the cell surface CXCR4 receptor.…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy Accelerates Diabetic Wound Closure

et al. 2014

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BackgroundNon-healing foot ulcers are the most common cause of non-traumatic amputation and hospitalization amongst diabetics in the developed world. Impaired wound neovascularization perpetuates a cycle of dysfunctional tissue repair and regeneration. Evidence implicates defective mobilization of marrow-derived progenitor cells (PCs) as a fundamental cause of impaired diabetic neovascularization. Currently, there are no FDA-approved therapies to address this defect. Here we report an endogenous PC strategy to improve diabetic wound neovascularization and closure through a combination therapy of AMD3100, which mobilizes marrow-derived PCs by competitively binding to the cell surface CXCR4 receptor, and PDGF-BB, which is a protein known to enhance cell growth, progenitor cell migration and angiogenesis.Methods and ResultsWounded mice were assigned to 1 of 5 experimental arms (n = 8/arm): saline treated wild-type, saline treated diabetic, AMD3100 treated diabetic, PDGF-BB treated diabetic, and AMD3100/PDGF-BB treated diabetic. Circulating PC number and wound vascularity were analyzed for each group (n = 8/group). Cellular function was assessed in the presence of AMD3100. Using a validated preclinical model of type II diabetic wound healing, we show that AMD3100 therapy (10 mg/kg; i.p. daily) alone can rescue diabetes-specific defects in PC mobilization, but cannot restore normal wound neovascularization. Through further investigation, we demonstrate an acquired trafficking-defect within AMD3100-treated diabetic PCs that can be rescued by PDGF-BB (2 μg; topical) supplementation within the wound environment. Finally, we determine that combination therapy restores diabetic wound neovascularization and accelerates time to wound closure by 40%.ConclusionsCombination AMD3100 and PDGF-BB therapy synergistically improves BM PC mobilization and trafficking, resulting in significantly improved diabetic wound closure and neovascularization. The success of this endogenous, cell-based strategy to improve diabetic wound healing using FDA-approved therapies is inherently translatable.

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Section: Discussionmentioning

confidence: 99%

Combination Therapy Accelerates Diabetic Wound Closure

et al. 2014

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“…These include alpha-tocopherol (Kurklu et al, 2011); Adiponectin ; Inhibin A (Perrien et al, 2011); Nerve growth factor via a hydrogel (Cao et al, 2011); Thrombin peptide 508 (Cakarer et al, 2010); Bone marrow progenitor cell mobilizing agent (Davidson et al, 2011); Calcium sulphate injection (Song et al, 2004); Osteoblast-like cells (Shao et al, 2007); Stromal cell derived factor-1 (Fujio et al, 2011); NEL-like molecule-1 (Xue et al, 2011).…”

Section: Locally Applied Agentsmentioning

confidence: 99%

Distraction Osteogenesis and Its Challenges in Bone Regeneration

Hamdy¹,

Rendon²,

Tabrizian³

2012

Bone Regeneration

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“…The ideal graft bone material should be similar to autologous bone tissue and provide osteogenesis, osteoinduction, and osteoconduction to the recipient site . During the osteogenesis process, the neovascularization is of great importance, which directly affecting the bone activity . In the present study, the rhBMP‐2 composite self‐curing calcium phosphate artificial bone material was used as a graft bone material.…”

Section: Discussionmentioning

confidence: 99%

“…12 During the osteogenesis process, the neovascularization is of great importance, which directly affecting the bone activity. 13 In the present study, the rhBMP-2 composite self-curing calcium phosphate artificial bone material was used as a graft bone material. It has a porous frame structure that is able to provide good conditions for rapid vascularization in the present study.…”

Section: Discussionmentioning

confidence: 99%

Studies of Superb Microvascular Imaging and Contrast‐Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration

Lin

Wang

et al. 2019

J of Ultrasound Medicine

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Objective The aim of this study was to investigate value of superb microvascular imaging (SMI) and contrast‐enhanced ultrasonography (CEUS) in evaluating the neovascularization of early bone regeneration. Methods Twenty‐five Sprague‐Dawley male rats were implanted with recombinant human bone morphogenetic protein‐2/calcium phosphate cement (rhBMP‐2/) in the muscle space of the left hind limb near the femoral head to establish the rat model of intramuscular ectopic osteogenesis. Ultrasonography and pathologic analysis were performed on the 3rd, 7th, 14th, 21st, and 28th days after modeling. Two‐dimensional ultrasonography, SMI, and CEUS were used to assess neovascularization and bone formation. Results Pathologic examination showed that different levels of neovascularization were observed in the graft bone over time after modeling, which increased significantly from the 3rd to 14th day, and then gradually decreased. CEUS and SMI showed no obvious microvessels inside the graft bone on the 3rd day. On the 7th day after modeling, a small number of neovascular vessels were observed around the graft bone. On the 14th day, neovascularization was observed in both the peripheral and inner parts of the graft bone. The number of neovascular vessels inside the graft bone had decreased gradually by the 21st and 28th days. The results of SMI and CEUS indexes showed that the vascular index, peak intensity, enhancement intensity, and enhancement rate first increased and then decreased with time. Their peak points were found on the 14th day. Arrival time, time to peak, and enhancement time decreased gradually over time (P < .05). Conclusion The combined application of SMI and CEUS may be useful in evaluating the neovascularization of early osteoanagenesis.

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Augmenting Neovascularization Accelerates Distraction Osteogenesis

Abstract: Progenitor cell mobilization improves bone regeneration in a rat distraction model. Furthermore, because this effect is seen in healthy bone and in ischemic bone healing during distraction, the mechanism is not merely related to oxygenation, but could be a phenomenon of fluid flow.

Cited by 17 publications

References 28 publications

Combination Therapy Accelerates Diabetic Wound Closure

Combination Therapy Accelerates Diabetic Wound Closure

Distraction Osteogenesis and Its Challenges in Bone Regeneration

Studies of Superb Microvascular Imaging and Contrast‐Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration

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