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

Figure 7. Application of 4D printed in bone defects. (A) Shape recovery behavior of the 4D-printed structure in a magnetic field and their application for
bone repair [116] . Copyright 2019, Elsevier. (B) A functional multi-responsive bilayer morphing membrane used for bone repair and bone formation [108] .
Copyright 2021, Wiley-VCH.

regeneration [33,152] , intestinal defect repair , enophthalmic implantation. This method is simple, but the drug release
[85]
invagination [153] , and others (Figure 9B–D). By implanting rate is difficult to control, and intelligent on-demand
4D dynamic scaffolds in minimally invasive therapy, in situ release cannot be achieved. Another way is to design
damage to tissues can be avoided, which greatly improves intelligent polymer networks or deformable devices
the post-operative comfort of patients [154] . Meanwhile, with 4D printing. They can be actuated by physiological
4D implants can conform to irregular tissue defects stimulation in vivo or remote stimulation in vitro after
perfectly. Besides, 4D printing is able to reconstruct some being implanted to release drugs autonomously and
cavities or parenchyma organs dynamically. 4D-printed controllably. For example, Zu et al. designed a bioinspired
implants show great potentials in tissue restoration and smart hydrogel capsule via extrusion-based 4D printing,
reconstruction, and promote significant progress for tissue consisting of UV crosslinked PNIPAM hydrogel as the
engineering. shell and drugs as the core (Figure 10A). The drugs can
release controllably based on the ambient temperature,
5.4. Drug delivery and the release profile can be modified by adjusting the
There are two methods to deliver drugs in 4D-printed internal pore size of hydrogel capsules [155] . The 4D-printed
implanted devices. One is to add targeted drugs in the core-shell structure is an applicable device to deliver
initial bioink [144] , and drugs can release after scaffold drugs on demand [156] . Hu et al. reported a pH-responsive

Volume 9 Issue 5 (2023) 328 https://doi.org/10.18063/ijb.764