Factors Influencing Successful Outcome in the Arteriovenous Loop Model: A Retrospective Study of 612 Loop Operations

Polykandriotis, Elias; Drakotos, Dimitris; Arkudas, Andreas; Pryymachuk, Galyna; Rath, Subha Narayan; Beier, Justus P.; Klumpp, Dorothee; Dragu, Adrian; Horch, Raymund E.; Kneser, Ulrich

doi:10.1055/s-0030-1267385

Cited by 13 publications

(10 citation statements)

References 11 publications

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“…The patency rate of the EPI-loop model after 8 weeks in vivo (70% with n = 20) was considerably lower than the patency rate of the common AV-loop after 8 weeks in vivo (82% with n = 11, all operations conducted by the same microsurgeon) [34]. A reason for the lower patency rate could be the learning curve which naturally leads to lower patency rates during the establishment phase of microsurgical models.…”

Section: Discussionmentioning

confidence: 99%

Myogenic Differentiation of Mesenchymal Stem Cells in a Newly Developed Neurotised AV-Loop Model

Bitto

Klumpp

Lange

et al. 2013

BioMed Research International

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Generation of axially vascularized muscle tissue constitutes a promising new approach to restoration of damaged muscle tissue. Mesenchymal stemcells (MSC), with their ability to be expanded to large cell numbers without losing their differentiation capacity into the myogenic lineage, could offer a promising cell source to generate neomuscle tissue. In vitro experiments showed that cocultures of primary myoblasts and MSC undergo myogenic differentiation by stimulation with bFGF and dexamethasone. A newly developed AV-Loop model with neurotization was established in this study. It encompasses axial vascularization and the additional implantation of a motor nerve serving as myogenic stimulator. Myoblasts and MSCs were coimplantated in a prevascularized isolation chamber. Cells were differentiated by addition of bFGF and dexamethasone plus implantation of a motor nerve. After 8 weeks, we could observe areas of myogenic differentiation with α-sarcomeric actin and MHC expression in the constructs. Quantitative PCR analysis showed an expression of myogenic markers in all specimens. Thus, neurotization and addition of bFGF and dexamethasone allow myogenic differentiation of MSC in an axially vascularized in vivo model for the first time. These findings are a new step towards clinical applicability of skeletal muscle tissue engineering and display its potential for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Myogenic Differentiation of Mesenchymal Stem Cells in a Newly Developed Neurotised AV-Loop Model

Bitto

Klumpp

Lange

et al. 2013

BioMed Research International

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“…Other groups therefore have introduced more surgical approaches by creating a vascular network first and then transplant completely vascularized constructs using arterial and venous loop models. Such models are by far more complex and depend on an enormous microsurgical expertise to guarantee successful vascular connections on an supramicrosurgical level . Utilizing this technique in small animal models and in a clinically relevant scale in large animal models , first clinical results with long‐term success over more than 4 years are now on the verge.…”

Section: Introductionmentioning

confidence: 99%

Tissue engineering and regenerative medicine –where do we stand?

Horch

Kneser

Polykandriotis

et al. 2012

J Cellular Molecular Medi

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Tissue Engineering (TE) in the context of Regenerative Medicine (RM) has been hailed for many years as one of the most important topics in medicine in the twenty-first century. While the first clinically relevant TE efforts were mainly concerned with the generation of bioengineered skin substitutes, subsequently TE applications have been continuously extended to a wide variety of tissues and organs. The advent of either embryonic or mesenchymal adult stem-cell technology has fostered many of the efforts to combine this promising tool with TE approaches and has merged the field into the term Regenerative Medicine. As a typical example in translational medicine, the discovery of a new type of cells called Telocytes that have been described in many organs and have been detected by electron microscopy opens another gate to RM. Besides cell-therapy strategies, the application of gene therapy combined with TE has been investigated to generate tissues and organs. The vascularization of constructs plays a crucial role besides the matrix and cell substitutes. Therefore, novel in vivo models of vascularization have evolved allowing axial vascularization with subsequent transplantation of constructs. This article is intended to give an overview over some of the most recent developments and possible applications in RM through the perspective of TE achievements and cellular research. The synthesis of TE with innovative methods of molecular biology and stem-cell technology appears to be very promising.

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“…A retrospective analysis of more than 600 AV loop surgeries showed a significant correlation of experience and practice of microsurgeons and the thrombosis rate and time of surgery [58]. For the reduction of vessel thrombosis, a range of different antiplatelet and/or anticoagulant drugs can be applied in the postoperative phase such as heparin, sodium-enoxaparin, or clopidogrel [18,24,59].…”

Section: Challengesmentioning

confidence: 99%

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

et al. 2018

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Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.

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Factors Influencing Successful Outcome in the Arteriovenous Loop Model: A Retrospective Study of 612 Loop Operations

Cited by 13 publications

References 11 publications

Myogenic Differentiation of Mesenchymal Stem Cells in a Newly Developed Neurotised AV-Loop Model

Myogenic Differentiation of Mesenchymal Stem Cells in a Newly Developed Neurotised AV-Loop Model

Tissue engineering and regenerative medicine –where do we stand?

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

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