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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
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