Haemodynamically stimulated and in vivo generated axially vascularized soft‐tissue free flaps for closure of complex defects: Evaluation in a small animal model

Abstract

The arteriovenous (AV) loop model permits the creation of significant volumes of axially vascularized tissue that represents an alternative to conventional free flaps, circumventing their common limitations. However, such AV loop-based flaps have never before been examined in standardized animal models with respect to their suitability for reconstruction of critical bone-exposing defects. In the course of our preliminary studies, we implemented a novel defect model in rats that provides standardized and critical wound conditions and evaluated whether AV loop-generated flaps are suitable for free microsurgical transfer and closure of composite defects. We compared three groups of rodents with similar scapular defects: one received the AV flap, whereas controls were left to heal by secondary intention or with supplementary acellular matrix alone. To create the flaps, AV loops were placed into subcutaneous Teflon chambers filled with acellular matrix and transferred to the thigh region. Flap maturation was evaluated by histological analysis of angiogenesis and cell migration at days 14 and 28 after loop creation. Flap transfer to the scapular region and microsurgical anastomoses were performed after 14 days. Postoperative defect closure and perfusion were continually compared between groups. Within the AV flap chamber, the mean vessel number, cell count and the proportion of proliferating cells increased significantly over time. The novel defect model revealed that stable wound coverage with homogeneous vascular integration was achieved by AV loop-vascularized soft-tissue free flaps compared with controls. In summary, our study indicates for the first time that complex composite defects in rats can successfully be treated with AV loop-based free flaps.

MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo

“…The data presented here may also be applicable in future translational studies in the field of tissue engineering. The AV loop model is a reliable tissue engineering technique for creation of vascularized and transplantable soft tissue units and has a great potential for successful translation from animal models into clinical trials in the future [82]. The miRNA profile and specific candidate genes we report, can serve as targets for selective enhancement of neovascularization using synthetic miRNA-mimics or antagomirs.…”

Acellular Human Placenta Small-Diameter Vessels as a Favorable Source of Super-Microsurgical Vascular Replacements: A Proof of Concept

“…In the context of tissue engineering, the creation of an AVL by interposing a vein graft between the saphenous vein and artery can be used for axial neovascularization of bioartificial tissue. Within the AVL, the autologous interposed vein graft is exposed to an arterial flow pattern, which stimulates angio-inductive properties and promotes neovascularization [ 21 , 43 ]. Recent studies have shown that the vein graft is the crucial effector of early angiogenesis during the neovascularization of a fibrin matrix [ 35 ].…”

“…The AVL chamber model facilitated the investigation of human placenta vessel engraftment in a high-flow system isolated from the surrounding tissue. Briefly, each AVL was generated using a decellularized human placenta vessel graft (hPG) anastomosed end-to-end between the right saphenous artery and vein with 11-0 Ethilon sutures (Ethicon, Somerville, NJ, USA) as previously published [ 21 ]. The AVL was subsequently placed into an isolation chamber and embedded in 2 layers of Matriderm ® , an acellular dermal matrix consisting of bovine collagen and elastin ( Figure 2 A–F).…”

Prefabrication—a Vascularized Skin Flap Using an Arteriovenous LoopPrefabricated Flap With Arteriovenous Loop

“…In 2012, Ding et al 8 further modified the arteriovenous loop for flap prefabrication by anastomosing the rat's caudal vein graft to the superficial iliac circumflex vein and the femoral artery. In 2018, Schmidt et al 17 combined arteriovenous loop with tissue engineering to prefabricate flaps that successfully repaired a distant complex tissue defect in rats. These reports show an arteriovenous loop can serve as a vascular pedicle for flap prefabrication.…”