Exploiting light-based 3D-printing for the fabrication of mechanically enhanced, patient-specific aortic grafts.

Despite polyester vascular grafts being routinely used in life-saving aortic aneurysm surgeries, they are less compliant than the healthy, native human aorta. This mismatch in mechanical behaviour has been associated with disruption of haemodynamics contributing to several long-term cardiovascular complications. Moreover, current fabrication approaches mean that opportunities to personalise grafts to the individual anatomical features are limited. Various modifications to graft design have been investigated to overcome such limitations; yet optimal graft functionality remains to be achieved. This study reports on the development and characterisation of an alternative vascular graft material. An alginate:PEGDA (AL:PE) interpenetrating polymer network (IPN) hydrogel has been produced with uniaxial tensile tests revealing similar strength and stiffness (0.39 ± 0.05 MPa and 1.61 ± 0.19 MPa, respectively) to the human aorta. Moreover, AL:PE tubular conduits of similar geometrical dimensions to segments of the aorta were produced, either via conventional moulding methods or stereolithography (SLA) 3D-printing. While both fabrication methods successfully demonstrated AL:PE hydrogel production, SLA 3D-printing was more easily adaptable to the fabrication of complex structures without the need of specific moulds or further post-processing. Additionally, most 3D-printed AL:PE hydrogel tubular conduits sustained, without failure, compression up to 50% their outer diameter and returned to their original shape upon load removal, thereby exhibiting promising behaviour that could withstand pulsatile pressure in vivo. Overall, these results suggest that this AL:PE IPN hydrogel formulation in combination with 3D-printing, has great potential for accelerating progress towards personalised and mechanically-matched aortic grafts.

Investigating multi-material hydrogel three-dimensional printing for in vitro representation of the neo-vasculature of solid tumours: a comprehensive mechanical analysis and assessment of nitric oxide release from human umbilical vein endothelial cells.

Many solid tumours (e.g. sarcoma, carcinoma and lymphoma) form a disorganized neo-vasculature that initiates uncontrolled vessel formation to support tumour growth. The complexity of these environments poses a significant challenge for tumour medicine research. While animal models are commonly used to address some of these challenges, they are time-consuming and raise ethical concerns. In vitro microphysiological systems have been explored as an alternative, but their production typically requires multi-step lithographic processes that limit their production. In this work, a novel approach to rapidly develop multi-material tissue-mimicking, cell-compatible platforms able to represent the complexity of a solid tumour's neo-vasculature is investigated via stereolithography three-dimensional printing. To do so, a series of acrylate resins that yield covalently photo-cross-linked hydrogels with healthy and diseased mechano-acoustic tissue-mimicking properties are designed and characterized. The potential viability of these materials to displace animal testing in preclinical research is assessed by studying the morphology, actin expression, focal adhesions and nitric oxide release of human umbilical vein endothelial cells. These materials are exploited to produce a simplified multi-material three-dimensional printed model of the neo-vasculature of a solid tumour, demonstrating the potential of our approach to replicate the complexity of solid tumours in vitro without the need for animal testing.