3D Printing of Noncytotoxic High-Resolution Microchannels in Bisphenol-A Ethoxylate Dimethacrylate Tissue-Mimicking Materials.

The ability to create cell-laden fluidic models that mimic the geometries and physical properties of vascularized tissue would be extremely beneficial to the study of disease etiologies and future therapies, including in the case of cancer where there is increasing interest in studying alterations to the microvasculature. Engineered systems can present significant advantages over animal studies, alleviating challenges associated with variable complexity and control. Three-dimensional (3D)-printable tissue-mimicking hydrogels can offer an alternative, where control of the biophysical properties of the materials can be achieved. Hydrogel-based systems that can recreate complex 3D structures and channels with diameters <500 µm are challenging to produce. We present a noncytotoxic photo-responsive hydrogel that supports 3D printing of complex 3D structures with microchannels down to 150 µm in diameter. Fine tuning of the 3D-printing process has allowed the production of complex structures, where for demonstration purposes we present a helical channel with diameters between 250 and 370 µm around a central channel of 150 µm in diameter in materials with mechanical and acoustic properties that closely replicate those of tissue. The ability to control and accurately reproduce the complex features of the microvasculature has value across a wide range of biomedical applications, especially when the materials involved accurately mimic the physical properties of tissue. An approach that is additionally cell compatible provides a unique setup that can be exploited to study aspects of biomedical research with an unprecedented level of accuracy.

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.