The venous graft as an effector of early angiogenesis in a fibrin matrix

Polykandriotis, Elias; Tjiawi, J.; Euler, Simon A.; Arkudas, Andreas; Heß, Andreas; Brune, Kay; Greil, Peter; Lametschwandtner, Alois; Horch, Raymund E.; Kneser, Ulrich

doi:10.1016/j.mvr.2007.04.003

Cited by 81 publications

(104 citation statements)

References 26 publications

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“…Assessment of vascularization patterns, however, requires valid morphological techniques such as corrosion casting. After microdissection to expose the vascular axis, SEM of corrosion casts is a more accurate method to quantify luminal sprouting than histology or macroscopically evaluated casts (30). Recently we observed a higher density of vascular sprouts in the venous proportion of the AVL in a morphometric study of vascular corrosion casts (30).…”

Section: Discussionmentioning

confidence: 97%

Fibrin Gel-Immobilized VEGF and bFGF Efficiently Stimulate Angiogenesis in the AV Loop Model

Arkudas¹,

Tjiawi²,

Bleiziffer³

et al. 2007

Mol Med

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The modulation of angiogenic processes in matrices is of great interest in tissue engineering. We assessed the angiogenic effects of fibrin-immobilized VEGF and bFGF in an arteriovenous loop (AVL) model in 22 AVLs created between the femoral artery and vein in rats. The loops were placed in isolation chambers and were embedded in 500 µL fibrin gel (FG) (group A) or in 500 µL FG loaded with 0.1 ng/µL VEGF and 0.1 ng/µL bFGF (group B). After two and four weeks specimens were explanted and investigated using histological, morphometrical, and ultramorphological [scanning electron microscope (SEM) of vascular corrosion replicas] techniques. In both groups, the AVL induced formation of densely vascularized connective tissue with differentiated and functional vessels inside the fibrin matrix. VEGF and bFGF induced significantly higher absolute and relative vascular density and a faster resorption of the fibrin matrix. SEM analysis in both groups revealed characteristics of an immature vascular bed, with a higher vascular density in group B. VEGF and bFGF efficiently stimulated sprouting of blood vessels in the AVL model. The implantation of vascular carriers into given growth factor-loaded matrix volumes may eventually allow efficient generation of axially vascularized, tissue-engineered composites.

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Section: Discussionmentioning

confidence: 97%

Fibrin Gel-Immobilized VEGF and bFGF Efficiently Stimulate Angiogenesis in the AV Loop Model

Arkudas¹,

Tjiawi²,

Bleiziffer³

et al. 2007

Mol Med

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“…19 We used an explantation time point of 3 weeks because of previous studies of our group showing direct luminal sprouting in the AVL model between days 10 and 14. 25 It has been observed that using a plain fibrin gel matrix in the AVL model with or without adding angiogenic growth factors, after 1 week, no luminal sprouting occurs. 17 Moreover, recent studies have demonstrated axially vascularization of different bone scaffolds such as custom-made processed bovine cancellous bone matrix, particulated porous hydroxyapatite, and beta-tricalcium phosphate matrix using the AVL model.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 It is known that the venous and the graft segments of the AVL are responsible for early angiogenesis up to day 14. 25 The thick tunica media of the artery was thought to avoid vascular sprouting at early stages after AVL construction. In this study, there was no detectable difference between the arterial and venous parts of the AVL in the histological evaluation.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Angiogenesis of Bioactive Glass in the Arteriovenous Loop Model

Arkudas¹,

Balzer²,

Buehrer³

et al. 2013

Tissue Engineering Part C: Methods

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In this study, the angiogenetic effect of sintered 45S5 Bioglass Ò was quantitatively assessed for the first time in the arteriovenous loop (AVL) model. An AVL was created by interposition of a venous graft from the contralateral side between the femoral artery and vein in the medial thigh of eight rats. The loop was placed in a Teflon isolation chamber and was embedded in a sintered 45S5 Bioglass Ò granula matrix filled with fibrin gel. Specimens were investigated 3 weeks postoperatively by means of microcomputed tomography, histological, and morphometrical techniques. All animals tolerated the operations well. At 3 weeks, both microcomputed tomography and histology demonstrated a dense network of newly formed vessels originating from the AVL. All constructs were filled with cell-rich, highly vascularized connective tissue around the vascular axis. Analysis of vessel diameter revealed constant small vessel diameters, indicating immature new vessel sprouts. This study shows for the first time axial vascularization of a sintered 45S5 Bioglass Ò granula matrix. After 3 weeks, the newly generated vascular network already interfused most parts of the scaffolds and showed signs of immaturity. The intrinsic type of vascularization allows transplantation of the entire construct using the AVL pedicle.

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“…Reconstructive surgeons therefore aim to generate so-called 'axially vascularized' tissues that could be transferred to the defect site using microsurgical techniques of vascular anastomosis. Since the initial description of the AV loop by Erol and Spira (1979), the superiority of the AV loop as a vascular carrier for an axial type of vascularization has been clearly demonstrated (Kneser et al, 2006;Polykandriotis et al, 2006Polykandriotis et al, , 2007. In a clinical scenario, the need for vascularized bone substitute emerges in cases with very large and/or complicated (e.g.…”

Section: Discussionmentioning

confidence: 99%

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

Beier¹,

Horch²,

Heß

et al. 2010

J Tissue Eng Regen Med

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Vascularization still remains an obstacle to engineering of bone tissue with clinically relevant dimensions. Our aim was to induce axial vascularization in a large volume of a clinically approved biphasic calcium phosphate ceramic by transferring the arteriovenous (AV) loop approach to a large animal model. HA/β-TCP granula were mixed with fibrin gel for a total volume of 16 cm 3 , followed by incorporation into an isolation chamber together with an AV loop. The chambers were implanted into the groins of merino sheep and the development of vascularization was monitored by sequential non-invasive magnetic resonance imaging (MRI). The chambers were explanted after 6 and 12 weeks, the pedicle was perfused with contrast agent and specimens were subjected to micro-computed tomography (µ-CT) scan and histological analysis. Sequential MRI demonstrated a significantly increased perfusion in the HA/β-TCP matrices over time. Micro-CT scans and histology confirmed successful axial vascularization of HA/β-TCP constructs. This study demonstrates, for the first time, successful axial vascularization of a clinically approved bone substitute with a significant volume in a large animal model by means of a microsurgically created AV loop, thus paving the way for the first microsurgical transplantation of a tissue-engineered, axially vascularized bone with clinically relevant dimensions.

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The venous graft as an effector of early angiogenesis in a fibrin matrix

Cited by 81 publications

References 26 publications

Fibrin Gel-Immobilized VEGF and bFGF Efficiently Stimulate Angiogenesis in the AV Loop Model

Fibrin Gel-Immobilized VEGF and bFGF Efficiently Stimulate Angiogenesis in the AV Loop Model

Evaluation of Angiogenesis of Bioactive Glass in the Arteriovenous Loop Model

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

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