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International Journal of Bioprinting Review of 4D-printed smart medical implants
Figure 4. Gradient and origami structure design in 4D printing. (A) Gradient structural design, a) Crosslinking gradient in a photocuring hydrogel formed
[91]
under UV light due to the different distance to light source . Copyright 2022, Elsevier. b) Graded structures based on LCEs by means of regulating
[92]
printing parameters (such as printing speed, and printing direction) . Copyright 2020, American Chemical Society. (B) Origami structural design,
origami structures for minimally invasive surgeries with high recovery [103] . Copyright 2021, MDPI. PI: Photoinitiator.
bend, curve , and then form a helix . Though these Through bi-/multi-layer design, self-bending, self-
[87]
[86]
deformations are internally driven by internal stress, we rolling, and self-buckling structures activated by moisture,
attribute them to these categories because their external light, pH, and so forth can be easily prepared. This
actuation is light, heat, and some other stimulus. establishes a foundation to utilize 4D-printed implants to
repair lumen organs such as vessels, trachea, intestines,
Based on these design principles, shape-morphing
behaviors are initiated in multi-layer structures. As shown and organs with a curved surface topology such as the
in Figure 3B, Ding et al. designed a trilayer structure heart and others. The range of materials available for the
consisting of two outer oxidized methacrylated alginate preparation of 4D printing implants has also been widened
layers with different swelling and degradation capacities to the elastomer, which supports the generation of implants
and a GelMA layer. Due to the anisotropic swelling of with higher toughness and strength when necessary.
the three layers and degradation of the fast-degradation Meanwhile, the fabrication of multi-layer structures
layer, the structure underwent five phases of deformation. permits the reconstruction of complex biological tissues.
More interestingly, due to reversible ionic crosslinking, the 4.2.2. Gradient structure design
remaining double-layer structure can deform reversibly in The formation of gradient structures has great prospects
2+
calcium ions (Ca ) and tetraacetic acid, respectively [88,89] .
in the production of 4D programmed scaffolds. It facilitates
More complex programmed deformation (such as the 4D deformation of single-layer structures. For
local buckling, curling, etc.) can be achieved through photocuring bioinks, crosslinking density attenuates with
partial pattern design in the printing of bi-/multi-layer the increase of distance along the light irradiation path in the
strips [81,84,85] . In these driving designs mentioned above, presence of a photoinitiator and ultraviolet absorber. Thus,
finite element analysis (FEA) simulations are conducted the gradient in crosslinking density can be created. The
to predict shape transformations which can effectively upper portion of hydrogel closest to a light source presents
calculate the effect of each parameter on shape morphing higher crosslinking density, while the lower part presents
according to mathematical models based on deformation a lower crosslinking degree. Under this circumstance, the
mechanisms [76,84] . resultant anisotropic swelling induces inner strain that
prompts deformation [12,90,91] (Figure 4Aa). For SMPs and
Volume 9 Issue 5 (2023) 321 https://doi.org/10.18063/ijb.764

