Page 331 - IJB-9-5

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

Figure 5. The application of 4D-printed implants in the body.

structural 4D changes, including body fluid, temperature, thus promoting the release of encapsulated insulin,
[23]
pH, biochemicals, and more . Specifically, the design of further promoting the healing of diabetes wounds [115] .
smart implants responsive to humoral stimulation mainly In addition, extracorporeal remote stimulus (including
depends on anisotropic swelling characteristics within the magnetism [112,116] , light, local temperature [108] , etc.) can
entire structure, as mentioned. Body temperature is around also induce 4D deformation after implants are implanted
37°C. Materials that respond to body temperature include into the body.
SMPs, PNIPAM hydrogel, and others. Some studies have All in all, basic models of different implant sites
explored SMPs with shape transition temperatures close can be obtained according to clinical imaging, and
to body temperature, such as poly (glycerol dodecanoate) then smart implants are pre-programmed to meet the
acrylate (PGDA) [111] and polyurethane using a specific needs of implantation sites. Relying on external and
synthesis method [113] . Intravascular implants thus internal stimulation, 4D deformation of implants can be
obtained show satisfactory deformation effects in vitro realized both before and after they are implanted into the
devices or in vivo environments. Gastric and intestinal body, which can satisfy intelligent adaptive repair and
juice present different pH values, and the pH-induced replacement of different tissue defects.
deformation depends on different swelling behaviors
[23]
of hydrogels under acidic or alkaline conditions . For 5.2. 4D printing cellular scaffolds
example, researchers used a type of hydrogel containing There are two types of 4D printing scaffolds with cells:
a large number of carboxyl groups on the side chain, cell-laden scaffolds and cell-seeding scaffolds. The cell-
and high and low swelling properties under alkaline laden scaffolds are defined as synchronous 4D printing
and acidic conditions are caused due to ionization and of biomaterials and cells. Commonly used biomaterials
deionization effects under different pH conditions. Thus, contain gelatin, GelMA, collagen, alginate, poly (ethylene
pH-driven expansion, contraction, and torsion can be glycol) (PEG), de-cellularized extracellular matrices
achieved [114] . Biochemical signals are an important part (dECMs), and others. The physicochemical properties of
of dynamic environments in vivo. The exploration of these 4D dynamic materials can be modulated by external
biochemical-sensitive implants is thus a research focus. stimulus over time and act as guidance on the behavior
Concerning this, researchers have prepared a glucose- of embedded cells [117,118] to reconstruct dynamic natural
responsive hydrogel network. High glucose concentration cellular microenvironments [119] . For example, protein-
can affect the crosslinking density of the micronetwork, polymer hydrogel biomaterials prepared by Liu et al.

Volume 9 Issue 5 (2023) 323 https://doi.org/10.18063/ijb.764