Engineering of Vascularized Transplantable Bone Tissues: Induction of Axial Vascularization in an Osteoconductive Matrix Using an Arteriovenous Loop

Kneser, Ulrich; Polykandriotis, Elias; Ohnolz, J.; Heidner, Kristina; Grabinger, Lucia; Euler, Simon A.; Amann, Kerstin; Heß, Andreas; Brune, Kay; Greil, Peter; Horch, Raymund E.

doi:10.1089/ten.2006.12.ft-98

Cited by 53 publications

(79 citation statements)

References 28 publications

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“…Nevertheless, the majority of currently applied tissue-engineering approaches rely on the so-called 'extrinsic' mode of neovascularization. In this setting, the neovascular bed originates from the periphery of the construct, which should be implanted into a site of high vascularization potential (Kneser et al, 2006). Since oxygen and nutrition supply by diffusion is restricted to a maximum range of 200 µm into a given matrix (Goldstein et al, 2001), suboptimal initial vascularization often limits the survival of cells in the centre of large constructs.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…Histological analysis was performed as described previously (Kneser et al, 2006). Briefly, specimens were fixed in formalin, decalcified in EDTA solution, dehydrated in graded ethanols and embedded in paraffin.…”

Section: Histological Analysis Of Constructsmentioning

confidence: 99%

“…The axial type of blood supply allows the vascularization and transfer of biomaterials independently of local conditions at the recipient site. We could previously demonstrate axial vascularization of other bone substitutes in a small animal AV loop model, with matrices displaying a significant degree of vascularization 8 weeks after implantation (Kneser et al, 2006). These promising results have led to the pivotal question -whether de novo creation of axially vascularized bone tissues in a human body is possible by employing the AV loop/isolation chamber model.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Histological Analysis Of Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…13 Recently, our group managed to vascularize different bone scaffolds using this arteriovenous loop (AVL) model. 14,15 We also evaluated different angiogenic growth factors in this AVL model to enhance angiogenesis, and we were able to show an increased survival of osteoblasts in this model compared to extrinsic vascularized scaffolds. [16][17][18] 45S5 Bioglass Ò has been used to develop bone tissue scaffolds, and the effects of Bioglass Ò dissolution products to support angiogenesis by secretion of vascular endothelial growth factor (VEGF) have been reported.…”

Section: Introductionmentioning

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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Engineered Vascularized Flaps, Composed of Polymeric Soft Tissue and Live Bone, Repair Complex Tibial Defects

Redenski

Guo

Machour

et al. 2021

Adv Funct Materials

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Functional regeneration of complex large-scaled defects requires both softand hard-tissue grafts. Moreover, bone constructs within these grafts require an extensive vascular supply for survival and metabolism during the engraftment. Soft-tissue pedicles are often used to vascularize bony constructs. However, extensive autologous tissue-harvest required for the fabrication of these grafts remains a major procedural drawback. In the current work, a composite flap is fabricated using synthetic soft-tissue matrices and decellularized bone, combined in vivo to form de novo composite tissue with its own vascular supply. Pre-vascularization of the soft-tissue matrix using dental pulp stem cells (DPSCs) and human adipose microvascular endothelial cells (HAMECs) enhances vascular development within decellularized bones. In addition, osteogenic induction of bone constructs engineered using adipose derived mesenchymal stromal cells positively affects micro-capillary organization within the mineralized component of the neo-tissue. Eventually, these neo-tissues used as axial reconstructive flaps support long-term bone defect repair, as well as muscle defect bridging. The composite flaps described here may help eliminate invasive autologous tissue-harvest for patients in need of viable grafts for transplantation.

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Engineering of Vascularized Transplantable Bone Tissues: Induction of Axial Vascularization in an Osteoconductive Matrix Using an Arteriovenous Loop

Cited by 53 publications

References 28 publications

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

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

Evaluation of Angiogenesis of Bioactive Glass in the Arteriovenous Loop Model

Engineered Vascularized Flaps, Composed of Polymeric Soft Tissue and Live Bone, Repair Complex Tibial Defects

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