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International Journal of Bioprinting Review of 4D-printed smart medical implants

Figure 10. 4D-printed drug delivery devices. (A) 4D-printed core-shell structure consisting of UV crosslinked PNIPAM hydrogel as the shell and drugs as
the core for controlled drug release [155] . Copyright 2022, Elsevier. (B) A pH-responsive microcage for the capture and release of microparticles due to the
different pore sizes in the expanded and contracted states [114] . Copyright 2019, Wiley-VCH. PNIPAM: poly (N-isopropylacrylamide).

challenges. Firstly, available biomaterials are limited; implantation are all closely interlinked. Therefore, the
more materials with stimuli-responsive properties or accuracy of clinical imaging, development of modeling
existing materials with the potential for 4D structure software, controllability of deformation programming,
formation should be exploited. Biocompatibility and and development of the particular software to pre-
biodegradability of materials used need to be considered. simulate deformation in vivo all need to take effort
Degradation products of these materials, which are to reach.
often overlooked in previous studies, should be tested The 4D-printed implants have the ability to self-deform
via both in vivo and in vitro experiments to ensure in response to multiple physiological and extracorporeal
that they are harmless to the body as well. In addition, signals, and they are quite instructive for biomedical
implant infection must be prevented by design, such as applications. It still requires multi-disciplinary cooperation
coating implants during design, adding antibacterial to promote produced dynamic scaffolds from laboratory
agents in the printing ink, and others. Secondly, printing investigation to clinical practice.
technologies remain to be updated in order to implement
multi-materials, high-speed, and high-resolution 4D Acknowledgments
printing. Additionally, more response conditions related
to the internal environment, as well as non-contact None.
response conditions are required to explore continually
to expand application of 4D scaffolds in vivo. Meanwhile, Funding
reversibility and repeatability of stimuli-responsive
deformation of scaffolds need to be achieved as different This work was supported by National Natural Science
application condition requires. Finally, for the sake of Foundation of China (82270595, 32171402), the
personalized medical treatment, imaging information China Postdoctoral Science Foundation (BX20220393,
of defect tissues, corresponding modeling, subsequent 2022M723891), Key Research and Development
programming of 4D scaffold, and deformation after Program of Jiangsu Province (BE2022823, BE2021727),

Volume 9 Issue 5 (2023) 331 https://doi.org/10.18063/ijb.764