7th World Congress of Biomechanics, July 6-11, 2014 ...

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changes, especially in adventitial cells and cells of the vasa vasorum. ... increase in vasa vasorum length density and their structural disarrangement. Finally ...
7th World Congress of Biomechanics, July 6-11, 2014

Study of the human saphenous vein arterialization in a compact and automated ex vivo vessel culture system Marco Piola1, Francesca Prandi2, Maria Cristina Vinci2, Claudia Colussi3, Gianluca Polvani4, Maurizio Pesce2, Gianfranco Beniamino Fiore1 and Monica Soncini1 1

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy; Laboratorio di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino-IRCCS, Milan, Italy; 3 Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Rome, Italy 4 Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy. 2

Abstract: Ex vivo vessel culture platforms able to apply arterial-like pressure patterns to vein segments are crucial to solve the timely issue of saphenous vein (SV) graft patency reduction following CABG surgery. To mimic the early events of vessel arterialization, we used an ex vivo vessel culture platform (Fig 1.A-B), developed in our Laboratory [1], able to apply the desired pressure patterns to human SV segments. (Fig.1 C-D and E). The pulsatile pressure conditioning consists of a loading step, a pulsatile stimulation step (80-120 mmHg), an unloading step, and a recirculation phase. During the pulsatile stimulation, cells are subjected to circumferential stress/strain typical of the arterial circulation, but in the absence of shear stress. Twelve samples were subjected to CABG-like pressure stimulation (CABG-PS), while twelve samples were cultured under venous perfusion (VP) conditions (3 ml/min steady flow, and 5 mmHg). Our histological data (H&E and Masson’s tricrome) indicated a clear thinning of the SV wall (Fig.1F) and a marked enlargement of the luminal perimeter (Fig.1G). Interestingly, the cross-sectional area of the tissue did not change after 7 days of stimulation. These results demonstrate a reorganization of the cellular and extracellular matrix SV components during the early stage of the pathological adaptation of the SV to the new hemodynamic environment. Further, a decrease in the cell density was followed by a significant increase in cellular proliferation rate. We also observed a contribution of the CABG-PS to determine microscopic ruptures in the endothelial layer and smooth muscle cells rearrangement (Fig.1 C-D and E, white arrows). Exposure of SV segments to CABG-PS induced epigenetic changes, especially in adventitial cells and cells of the vasa vasorum. This correlated with an increase in vasa vasorum length density and their structural disarrangement. Finally, these changes were accompanied by up-regulation of MMP-2/9 and differential activation of TIMP-1. Taken together, these results showed that the application of pulsatile pressure was sufficient to induce a major structural rearrangement in the SV wall. This platform, here used to elucidate the

biomechanical-driven cellular and molecular mechanisms involved in SV arterialization, paves the way for new therapeutic treatments based on SV tissue conditioning.

[1] M. Piola, F. Prandi, N. Bono, M. Soncini, E. Penza, M. Agrifoglio, G. Polvani, M. Pesce, and G. B. Fiore. A compact and automated ex-vivo vessel culture system for the pulsatile pressure conditioning of human saphenous veins. Journal of Tissue Engineering and Regenerative Medicine, [Epub ahead of print] doi:10.1002/term.1798.