SRS217 - Modelling angiogenesis and tissue formation using the arteriovenous loop for vascularised tissue engineering

Abstract Introduction The clinical demand for vascularised tissues still remain unmet. Clinical case studies have utilised the arteriovenous loop (AVL) vascularise tissues. We show using histological methods and spatial transcriptomics the evolution of tissue grown with this model. Methods The surgical model used is the rodent arteriovenous loop model, where the rat femoral artery and vein is anastomosed together and placed in a chamber together with fibrin hydrogel. Tissue grown was analysed every 7 days till 28 days. Results There was a significant increase in the percentage of chamber filled with new tissue between day 7 and day 14 which was maintained till day 28 (9.44% ± 1.90 versus 43.58% ± 4.52, P = 0.01). This was accompanied by a similar increase in vessel density (16.96 ± 6.12 versus 154.6 ± 14.08, P = 0.01). Collagen deposition was later, only reaching a peak at day 28 for both red and yellow fibres. Preliminary analysis using spatial transcriptomics show the different stages of angiogenesis with a higher expression of VEGFA and ENG at day 7 and a higher expression of EPHB4 and NOTCH1 at day 28. There were also two different cell clusters representing different mechanisms of vascularisation, mesenchymal cells migrating from the AVL (intrinsic vascularisation) and macrophages through the chamber pores (extrinsic vascularisation). Conclusions We show that the AVL is a model for growing vascularised tissues and studying the mechanisms of angiogenesis and tissue formation in vivo. Further work will involve exploring the role of mesenchymal cells and macrophages in vascularisation and new tissue formation.