Page 330 - IJB-9-5

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

LCEs, the 4D transformation of gradient structures can be 5. Application
programmed by regulating printing parameters. Adjusting From first proposed in a TED talk [105] to subsequent
printing speed, printing path, and part geometry drives development, 4D printing brings great possibilities for tissue
their deformation patterns by graded thermal distribution replacement, restoration, and medically implanted devices
in a specific direction [92,93] (Figure 4Ab). The generation in biomedical fields. It is a huge step forward following 3D
of gradient structures broadens the design space of 4D printing, and it offers special advantages including but not
deformation constructs and has wide application prospects limited to (i) convenience in the implantation of minimally
in the field of tissue engineering.
invasive surgery due to flexible shape transformation;
4.2.3. Origami structure design (ii) seamless fit with defected tissues owing to programmed
Origami structures have extended their application in shape-morphing process after implanted; (iii) formation
the biomedical field owing to their self-deployment of bionic structures, and dynamic deformation conducive
ability, which can expand from a small-sized volume to cell adhesion, proliferation, and differentiation;
to a larger functional device. Despite the difficulties in (iv) realization of biomimetic behaviors in body tissues
fabricating their complex configurations, the emergence such as joint activity, muscle contraction, and relaxation;
of 4D printing technology reduces manual pressure and and (v) responsiveness to a physiological condition
facilitates the process. The folding modes are of great such as pH, body fluid, temperature, biochemicals, etc.
importance in origami-derived objects so they can be This section summarizes the application procedure of
designed to fold and unfold transversely or longitudinally. 4D-printed implants in vivo (Figure 5). Then, we focus on
The collapsible objects can be divided into a serious of the interaction of 4D printing scaffolds with cells (Table 1)
repeated foldable elements. Different flexible folding and the application of 4D-printed representative implants
processes can be achieved by designing these sub-units (Table 2).
and nearby creases. The choice of materials for these
constructs mostly relies on SMPs that enable them to 5.1. Application procedure
respond to thermal stimulation. The PLA stents formed by To apply 4D-printed implants in vivo on tailor-made
square elements and helical angles were built to self-deploy conditions, pre-modeling steps that detect anatomical
in large shrinkage ratios . Triangular- , hexagon- , structures of diseased sites with the assistance of clinical
[96]
[94]
[95]
honeycomb- , and hinge -shaped sub-units were also imaging information are needed first [106] . On this basis,
[98]
[97]
adopted in the deployable and reconfigurable structures. It implants are designed, and operational procedures are
is noteworthy that Manen et al. designed different types of planned [107] to allow the selection of optimized implantation
unit cells by regulating the printing path to form various approaches and subsequent deformation programming
origami-like deformed supports . Different folding before surgical intervention.
[99]
structures are produced through the design of creases, The deformation programs can be divided into two
such as connecting SMP to an elastomeric matrix at the types: (i) performing stimulus-responsive deformation in
crease [100] or programming precisely the local gradients advance and then implanting in vivo ; (ii) initiating in situ
[76]
in hydrogels by modifying irradiation direction and time deformation after implantation [108] . The former applies
of ultraviolet light [101] . Furthermore, by printing designed to the fabrication of some tubular and curved implants,
patterns on pre-stretched substrates, complex origami including tracheal , vascular [109] , intestinal implants ,
[85]
[76]
structures mimicking a butterfly, the Sydney Opera House, cardiac patches [110] , and more. Biomedical implants
a rose, and a dress with poly (dimethylsiloxane)-based conforming to specific physiological bending degrees
elastomer as materials were made [102] . It can thus be seen can be obtained as required through pre-programming
that various complex deformation processes can be realized and following stimulus-responsive deformation. 4D
through origami design. On this basis, origami structures printing technology provides faster, more intelligent, and
for minimally invasive surgeries with high recovery have more accurate preparation during this process. Potential
been created (Figure 4B) [103] . The generation of origami stimulus needed in the procedure can be easily acquired
structures enriches the deformation effect in 4D printing. in vitro. The latter has huge application value for minimally
The programmability, agile deformability, and self-assembly invasive surgery and all regular or irregular tissue defects
property position the origami structures as promising repair. Since it deforms after being implanted in vivo,
devices in a medical application [99,103,104] . It is of great the stimulation conditions are limited to physiological
application significance for minimally invasive surgery stimulus in vivo [111] and remote stimulus in vitro [112] . The
to design origami structural implants that match targeted body possesses a diverse physiological environment, and
organs or tissues as required. They can be implanted in the there are a variety of stimulation conditions that can drive
folded state and deploy automatically after being implanted.

Volume 9 Issue 5 (2023) 322 https://doi.org/10.18063/ijb.764