Current developments in multifunctional smart materials for 3D/4D bioprinting

Tissue engineering and regenerative medicine (TE&RM) has made continuous advancements by extending three-dimensional (3D) printing towards the development and fabrication of biomimetic scaffolds composed of biomimetic natural and synthetic materials. Although several clinical applications of 3D-printed scaffolds made of classical biomaterials have yielded promising results, current basic research trends have shifted towards rendering scaffolds “smart” or dynamically responsive where shape changes are induced by external stimulation (ie. electromagnetic radiation, mechanical stress, heat) or physiological changes in the local microenvironment through pre-designed mechanisms of action. Although a bulk of the research efforts have led to high-impact publications demonstrating the capabilities of these technologies, hardly any studies have been published illustrating the application of these research efforts in a clinical context. Herein, we will discuss current trends and advancements of 3D printable bioinks and highlight the most recent developments (2015-present) of 3D-printed smart materials also commonly referred to as 4D printing/programmable matter. We will conclude with a prospective opinion of this research field where innovation is synonymous with risk-taking. High-risk, high-reward research founded on revolutionary innovations are often disruptive and lead to new paradigms; conclusively the 4D printing can be disruptive, because it has the potential to change the current paradigm by changing the question from “what can we do with these materials/technologies?” to “how can we move the concept/technology forward to achieve what we need”.