Thermoresponsive Polymers with Reversible Sol–Gel Transition for 4D Bioprinting

High Resolution Image Download MS PowerPoint Slide In the last years, 3D bioprinting has gained great interest for the development of advanced models aimed at biological high-throughput studies. Despite the great potentialities, some technical challenges still need to be addressed. Among those is the necessity of creating a bioink formulation that can ensure high batch-to-batch replicability as well as good biocompatibility and mild curing conditions for cell encapsulation. Within this context, polymer formulations capable of reversible sol–gel transitions upon temperature changes, also termed thermoresponsive gelators, may represent an important advancement, enabling cell encapsulation in their liquid state and forming a self-standing 3D model by increasing the temperature. In addition, their possibility of responding to external stimuli, as native tissues are capable of, can pave the way to advanced applications, making these formulations extremely appealing for so-called 4D bioprinting. In this work, we developed a poly(ethylene glycol)-based thermoresponsive gelator undergoing a reversible sol–gel transition at 26 °C. We synthesized the polymer via reversible addition–fragmentation chain transfer (RAFT) polymerization. This provided excellent control over the polymer microstructure and in turn the possibility of systematically investigating its role on key physicochemical properties of the gelator, including the thermoresponsive and rheological behaviors. Finally, these formulations were validated in terms of printability through in situ imaging and biocompatibility. Then, they were tested as bioinks in the extrusion-based bioprintingof human umbilical vein endothelial cells, demonstrating their potential in 4D bioprinting applications, behaving as fugitive inks allowing the recovery of the cell component after application of temperature stimulation.