IN VIVO REGENERATION OF MICROVASCULAR PEDICLE

Objective: The difficulty of obtaining significant long-term patency and good wall mechanical strength in vivo has been a significant obstacle in achieving small-diameter vascular prostheses. The aim of the present study was to develop a prosthetic graft that could perform as a small diameter vascular conduit for artery and vein regeneration. Methods: 60 Male Wistar rats weighing 250-350g were used. Tubular structures of hyaluronan (HYAFF-11 tubules, 2 mm diameter, 1 cm length) were grafted in the abdominal aorta (n = 30), and in the vena cava (n = 30) of rats as temporary absorbable guides to promote regeneration of vascular structures. No anticoagulants were used either before or after the operation. Performance was assessed at 5, 15, 30, 60, 120, and 180 days after surgery by histology (haematoxylin-eosin and Weighert solution), immunohistochemistry (antibodies to von Willebrand factor, CD34, vascular endothelial growth factor receptor-2 and to Myosin Light Chain Kinase), and ultra-structural analysis. Results: These experiments resulted in three novel findings: 1) complete endothelialisation of the tube’s luminal surface occurred; 2) sequential regeneration of vascular components led to complete vascular wall regeneration 15 days after surgery; and 3) the biomaterial used created the ideal environment for the delicate regeneration process during the critical initial phases, yet its biodegradability allowed for complete degradation of the construct four months after implantation, at which time, a new artery and a new vein remained to connect the vascular stumps. This study assesses the feasibility to create a completely biodegradable vascular regeneration guide in vivo, able to sequentially orchestrate vascular regeneration events needed for very small artery and vein reconstruction. Conclusion: HYAFF-11 prosthesis opens new innovative possibilities of surgical treatment in the field of reconstructive microsurgery and paediatric vascular surgery, and a novel experimental model to study artery and vein in vivo regeneration processes.