Engineering Vascularized Transplantable Soft Tissue Free Flaps in Sheep Using the Arteriovenous Loop Technique

Abstract

The aim of this study was to grow axially vascularized soft tissue flaps in sheep using the arteriovenous loop (AVL) technique to be transplanted for defect reconstruction. This technique may be a promising alternative to conventional free flaps to further reduce flap donor site morbidity. In this pilot study, AVLs (n = 12) were created in the groins of six sheep, placed into an isolation chamber, and embedded in Matriderm®. Tissue volume, vascularization, and cell proliferation were assessed on postoperative day (POD) 28 using immunohistochemical staining and microcomputed tomography (µCT). Four AVL free flaps were microsurgically anastomosed to the neck vessels in a standardized defect sheep model on POD 28. Defect closure and intrinsically vascularized scaffold-based bioengineered flaps (IVSBs) flap perfusion were studied by angiography and histology 10 days after transplantation. One IVSB flap was lost due to chamber infection. At POD 28, the remaining 11 IVSB flaps had filled the isolation chamber. Histological examination and µCT analysis of seven IVSB flaps verified homogeneous microvascular networks within the flaps. The mean number of microvessels, vessel volume, and the percentage of proliferating cells increased significantly over time. In the defect model, all four transplanted flaps showed macroscopically, angiographically, and histologically stable defect closure 10 days after transplantation, with homogeneous vascular integration into the surrounding tissue. This pilot study demonstrates that in a large animal model complex, defects can be reconstructed using free IVSB flaps with a clinically relevant tissue volume. These data provide the preclinical proof prior to human application.

Impact Statement

Arteriovenous loop-based flaps in combination with a CE scaffold have the potential to become an alternative to conventional free flaps in humans offering minimal donor-site morbidity and promising therapeutic efficacy, particularly in patients with limited donor-site availability or those unsuitable for prolonged general anesthesia and extended surgical times.