A low-cost scalable 3D-printed sample-holder for agitation-based decellularization of biological tissues.

Decellularized extracellular matrix is one of the most promising biological scaffold supporting in vitro tissue growth and in vivo tissue regeneration in both preclinical research and clinical practice. In case of thick tissues or even organs, conventional static decellularization methods based on chemical or enzymatic treatments are not effective in removing the native cellular material without affecting the extracellular matrix. To overcome this limitation, dynamic decellularization methods, mostly based on perfusion and agitation, have been proposed. In this study, we developed a low-cost scalable 3D-printed sample-holder for agitation-based decellularization purposes, designed for treating multiple specimens simultaneously and for improving efficiency, homogeneity and reproducibility of the decellularization treatment with respect to conventional agitation-based approaches. In detail, the proposed sample-holder is able to house up to four specimens and, immersed in the decellularizing solution within a beaker placed on a magnetic stirrer, to expose them to convective flow, enhancing the solution transport through the specimens while protecting them. Computational fluid dynamics analyses were performed to investigate the fluid phenomena establishing within the beaker and to support the sample-holder design. Exploratory biological tests performed on human skin specimens demonstrated that the sample-holder reduces process duration and increases treatment homogeneity and reproducibility.

Hemodialysis arterio-venous graft design reducing the hemodynamic risk of vascular access dysfunction.

Although arterio-venous grafts (AVGs) represent the second choice as permanent vascular access for hemodialysis, this solution is still affected by a relevant failure rate due to graft thrombosis, and development of neointimal hyperplasia (IH) at the distal vein. As a key role in these processes has been attributed to the abnormal hemodynamics establishing in the distal vein, the optimization of AVGs design aimed at minimizing flow disturbances would reduce AVG hemodynamic-related risks. In this study we used computational fluid dynamics to investigate the impact of alternative AVG designs on the reduction of IH and thrombosis risk at the distal venous anastomosis. The performance of the newly designed AVGs was compared to that of commercially available devices. In detail, a total of eight AVG models in closed-loop configuration were constructed: two models resemble the commercially available straight conventional and helical-shaped AVGs; six models are characterized by the insertion of a flow divider (FD), straight or helical shaped, differently positioned inside the graft. Unfavorable hemodynamic conditions were analyzed by assessing the exposure to disturbed shear at the distal vein. Bulk flow was investigated in terms of helical blood flow features, potential thrombosis risk, and pressure drop over the graft. Findings from this study clearly show that using a helically-shaped FD located at the venous side of the graft could induce beneficial helical flow patterns that, minimizing flow disturbances, reduce the IH-related risk of failure at the distal vein, with a clinically irrelevant increase in thrombosis risk and pressure drop over the graft.