The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

Abstract

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.

Interdisciplinary Treatment of Breast Cancer After Mastectomy With Autologous Breast Reconstruction Using Abdominal Free Flaps in a University Teaching Hospital—A Standardized and Safe Procedure

“…Free microsurgical breast reconstruction with autologous tissue remains the gold standard in modern therapeutic strategies following mastectomy and especially when irradiation was performed during cancer treatment. Other techniques, such as tissue engineering and regenerative medicine, also including the prospect of three-dimensional printing, seem promising but have not reached the clinical applicability so far (12)(13)(14). In this retrospective study, we analyzed the outcome of 217 abdominal free flaps for autologous breast reconstruction in 193 patients with respect to the multisurgeon teaching aspect in a university hospital.…”

Keratinocyte Monolayers on Hyaluronic Acid Membranes as “Upside-Down” Grafts Reconstitute Full-Thickness Wounds

“…It seems logical that differentiated cells located in the upper cell layers on top of the membrane might not contribute to the wound healing capacity of cell transplantation clinically until cells are connected with the recipient microcirculation. Models to enhance performance of tissue engineered grafts via arterio-venous microvascular loops are promising, but are not suitable for skin replacement yet [22,23]. Many of these keratinocytes might be lost due to lack of nourishment as a result of inadequate diffusion hindered by the carrier in vivo .…”

Combining Vascularization Strategies in Tissue Engineering: The Faster Road to Success?

“…Moreover, they should rapidly vascularize to guarantee sufficient oxygen supply and, hence, cellular survival after their implantation into a tissue defect (Blinder et al, 2015;Cerino et al, 2017). In fact, the lack of an adequate vascularization is a major reason for the failure of particularly extensive and complex materials for the treatment of large-scale tissue defects (Maggi et al, 2003;Kneser et al, 2006;Leibig et al, 2016;Weigand et al, 2018;Yuan et al, 2018).…”

“…This approach has not only demonstrated promising results in various experimental studies (Lokmic et al, 2007(Lokmic et al, , 2008Beier et al, 2009;Arkudas et al, 2013;Weigand et al, 2018), but is also already applied in clinical practice (Wang and Chu, 1996;Asif et al, 2005;Laschke and Menger, 2016;Henn et al, 2019;Hernández-Enríquez et al, 2019;McEwan et al, 2019). The basic concept of this in situ strategy is the generation of an axially vascularized tissue using the patient's own body as a bioreactor (Reichenberger et al, 2010;Laschke and Menger, 2016;Radwan et al, 2018;Weigand et al, 2018). In detail, an anastomosis between an artery and vein results in an AV loop, which is subsequently transferred into an enclosed implantation chamber to provide an isolated in vivo environment ( Figure 1A) (Mian et al, 2000;Lokmic et al, 2008).…”