Synthetic vascular grafts to be applied as access grafts for hemodialysis often require anti-kinking properties. Previously, electrospun microporous vascular implants based on synthetic supramolecular materials have been shown to perform adequately as resorbable grafts due to the microstructures, thereby enabling attraction of endogenous cells and consecutive matrix production in situ. Here, we use supramolecular materials based on hydrogen bonding interactions between bisurea (BU) or 2-ureido-4[1H]-pyrimidinones (UPy) to produce microporous anti-kinking tubular structures by combining solution electrospinning with 3D printing. A custom-made rational axis for 3D printing was developed to produce controlled tubular structures with freedom in design in order to print complex tubular architectures without supporting structures. Two different tubular grafts were developed, both composed of a three-layered design with a 3D printed spiral sandwiched in between luminal and adventitial electrospun layers. One tubular scaffold was composed of BU-polycarbonate electrospun layers with 3D printed polycaprolactone (PCL) strands in between for dimensional stability, and the other graft fully consisted of supramolecular polymers, using chain-extended UPy-PCL as electrospun layers and a bifunctional UPy-PCL for 3D printing. Both grafts, with a 3D printed spiral, demonstrated a reproducible dimensional stability and anti-kinking behavior under bending stresses.

Abstract3D‐scaffold based in vitro human tissue models accelerate disease studies and screening of pharmaceutics while improving the clinical translation of findings. Here is reported the use of human induced pluripotent stem cell (hiPSC)‐derived vascular organoid cells as a new cell source for the creation of an electrospun polycaprolactone‐bisurea (PCL‐BU) 3D‐scaffold‐based, perfused human macrovessel model. A separation protocol is developed to obtain monocultures of organoid‐derived endothelial cells (ODECs) and mural cells (ODMCs) from hiPSC vascular organoids. Shear stress responses of ODECs versus HUVECs and barrier function (by trans endothelial electrical resistance) are measured. PCL‐BU scaffolds are seeded with ODECs and ODMCs, and tissue organization and flow adaptation are evaluated in a perfused bioreactor system. ODECs and ODMCs harvested from vascular organoids can be cryopreserved and expanded without loss of cell purity and proliferative capacity. ODECs are shear stress responsive and establish a functional barrier that self‐restores after the thrombin challenge. Static bioreactor culture of ODECs/ODMCs seeded scaffolds results in a biomimetic vascular bi‐layer hierarchy, which is preserved under laminar flow similar to scaffolds seeded with primary vascular cells. HiPSC‐derived vascular organoids can be used as a source of functional, flow‐adaptive vascular cells for the creation of 3D‐scaffold based human macrovascular models.

Background Replacement of diseased heart valves with the currently available valve prostheses has serious drawbacks. The use of bioresorbable synthetic “in situ tissue engineered” heart valve prostheses has been proposed to overcome the limitations of traditional heart valve prostheses. Such bioresorbable synthetic heart valve prostheses have been successfully tested as pulmonary valve replacements in preclinical studies, but data on aortic valve replacement is lacking. Here, we present the first in-vivo study on the long-term functionality of bioresorbable synthetic heart valves in the high-pressure circulation. Methods Approval for the animal studies was obtained by the Amsterdam University Medical Centres Animal Care Ethics Committee (AVD1180020197705) and are in agreement with the current Dutch law on animal experiments (WOD). We surgically implanted bioresorbable synthetic aortic valve prostheses in 20 female Swifter sheep in orthotopic position. The scheduled follow-up times were 1, 3, 6, 9 and 12 months. Results Fifteen sheep (75%) recovered well from the surgical valve implantation procedure and were included in this analysis. No sheep died due to valve failure. All valves remained free from active infectious endocarditis, thrombotic complications, and pathological calcification. A total of 10 valves (67%) were intact, thin and pliable and remained free from leaflet thickening, retraction and degradation up to 12 months after implantation. In most valves (67%), the scaffold remained sparsely- or unpopulated by cells during 12 months follow up. In some valves (33%), colonization of the valve scaffold was observed, however this was most often associated with partial degradation of the leaflet and leaflet thickening. In general, the degradation of the scaffold fibres was limited throughout the follow-up period. Conclusion We are the first to evaluate in vivo bioresorbable synthetic heart valves in aortic position. While valves remained functional, the study also serves as a starting point to further optimize scaffold and neotissue development for heart valve replacement in the high-pressure environment. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1. Cardiovasculair Onderzoek Nederland (grant number CVON2012-01)2. Netherlands Organization for Scientific Research (024.003.013)