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.



subject category

Materials Science, Multidisciplinary


Costa, PDC; Costa, DCS; Correia, TR; Gaspar, VM; Mano, JF

our authors


The authors would like to acknowledge the support of the European Research Council for project ATLAS, grant agreement ERC-2014-ADG-669858. The authors also acknowledge the support of European Union (EU) Horizon 2020 for the project InterLynk, Grant agreement: H2020-NMBP-TR-IND-2020, Project ID: 953169. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. This work was also supported by the Programa Operacional Competitividade e InternacionalizacAo (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects MARGEL (PTDC/BTM-MAT/31498/2017), MIMETic (FCT-POCI-01-0145-FEDER-031210), and PANGEIA (PTDC/BTM-SAL/30503/2017). The MARGEL project was acknowledged for the individual Junior Researcher contract of D.C.S.C. and M.Sc. Scholarship of P.D.C.C. The MIMETic project was acknowledged for the individual Junior Researcher contract of T.R.C. FCT was also acknowledged by financial support through an individual contract as Junior researcher attributed to V.M.G. (CEECIND/01410/2018).

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