Natural Origin Biomaterials for 4D Bioprinting Tissue-Like Constructs

Leveraging 4D biofabrication for engineering biomimetic living constructs is rapidly emerging as a valuable strategy for recapitulating native tissue dynamics, via on-demand stimuli, or in a naturally evolving mode. Carefully selecting smart materials with suitable responsiveness and cell-supporting functionalities is crucial to take full operational advantage of this next-generation technology. Recent endeavors combining naturally available polymers or hybrid smart materials improve the potential to manufacture volumetrically defined, cell-rich constructs that may display stimuli–responsive properties, shape memory/shape morphing features, and/or dynamic motion in time. In this review, natural origin biomaterials and the stimuli that can be exploited for granting dynamic morphological features and functionalities post-printing are highlighted. A broad overview of recent reports focusing on 4D-bioprinted constructs for tissue engineering and regenerative medicine is also provided and critically discussed in light of current challenges, as well as foreseeable advances. It is envisioned that upon assurance of key regulatory demands, such technology will become translatable to numerous biomedical applications that require fabrication of constructs with dynamic functionality.