Milica Radisic

Epicardial cells (EPIs) form the outer layer of the heart and play an important role in development and disease. Current heart‐on‐a‐chip platforms still do not fully mimic the native cardiac environment due to the absence of relevant cell types, such as EPIs. Here, using the Biowire II platform, we constructed engineered cardiac tissues with a defined epicardial outer layer and inner myocardial structure, and developed an image analysis approach to track the EPI cell migration in a beating myocardial environment. Functional properties of EPI cardiac tissues improved over two weeks in culture. In conditions mimicking ischemia reperfusion injury (IRI), the EPI cardiac tissues experienced less cell death and a lower impact on functional properties. EPI cell coverage was significantly reduced and more diffuse under normoxic conditions compared to the post‐IRI conditions. Upon IRI, migration of EPI cells into the cardiac tissue interior was observed, with contributions to smooth muscle positive cell population. Altogether, we designed a novel heart‐on‐a‐chip model that incorporates EPIs through a formation process that mimics cardiac development and demonstrated that EPI cardiac tissues respond to injury differently than epicardium‐free controls, highlighting the importance of including EPIs in heart‐on‐a‐chip constructs that aim to accurately mimic cardiac environment. This article is protected by copyright. All rights reserved

Artificial organs and organs‐on‐a‐chip (OoC) are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat‐photopolymerization (VP) 3D printing, but only low‐resolution structures have been produced so far. Here, a VP‐POMaC ink is introduced and 3D printing of 80 µm positive features and complex 3D structures is demonstrated using low‐cost (≈US$300) liquid‐crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink are tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility is assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D‐printed gyroid seeded with cells. VP‐POMaC and low‐cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering and 3D cell culture as demonstrated here, and possibly in OoC, implants, wearables, and soft robotics.