3.1.1. Shape-Memory Polymers
Shape memory polymers (SMPs) are a group of smart materials with the ability to inelastically deform to create metastable temporary shapes in response to an external stimulus such as light, moisture, or temperature change [
32,
43]. The SME can be controlled and programmed in SMPs, which makes them particularly useful for fabricating dynamic 4D structures [
27]. Their low cost, light weight, ease of processing, and high programming flexibility make SMPs suitable for use within various industries, including aerospace and manufacturing, but it is their biodegradability and biocompatibility that promote their use in fabricating biomedical devices [
35,
43,
46]. Since traditional manufacturing/processing of SMPs is still reliant on polymerisation, extrusion, and casting methods, additive manufacturing is an attractive alternative for fabricating these materials. This allows the creation of complex geometries and detailed structures [
32]. Various 3D printing technologies have succeeded in fabricating structures from both single polymers and SMP composites, as shown in
Table 2 [
35]. The most popular group of biodegradable SMPs, according to Wang et al., are polyesters such as poly (lactic acid) (PLA) and poly-caprolactone (PCL), and polyether urethane, which are also recommended by Mu et al. for their biocompatibility [
46,
52]. Their application in 4D printing has attracted considerable attention in recent years. SMPs and their composites have shown potential for use as thrombus cleaners, surgical sutures, intravascular stents, and aneurysm occluders. Traditional 3D printing techniques use highly cross-linked thermoset polymer resins, resulting in hard and rigid 3D structures. To obtain the SME required of 4D-printed structures, dual-component polymers are used, which consist of a monofunctional monomer resin and a cross-linking oligomer resin [
32]. The mono-functional monomer forms the linear backbone of the polymer chain. The two broad features causing shape memory behaviour in these SMPs are net-points (hard components) and switching segments (soft components) [
8,
32]. The traditional thermomechanical training of SMPs involves six steps, as shown in
Figure 7.
- (1)
Heating the 3D printed structure above the glass transition temperature (Tg)
- (2)
Applying mechanical load to form the deformed configuration
- (3)
Cooling below Tg to "set" the temporary shape
- (4)
Removing load,
- (5)
Actuation
- (6)
Cooling
Upon heating the material above its SME initiation temperature (e.g., T
g), the monomer (soft component) facilitates plastic deformation into the temporary structure while the crosslinking oligomer (hard component) retains the "shape-memory" of the original printed configuration through thermally-stable covalent bonds [
32]. Constant application of a mechanical force to deform the structure while cooling below T
g will programme the temporary shape into the material. This fixes the kinetics of the material into a higher energy state resulting in higher internal energy than that of the original structure [
26,
27]. Once exposed to the external stimulus (e.g., reheating above T
g), the material can surpass the kinetic barriers by releasing the motion of the polymer chain segments, and the structure will recover to its permanent shape [
18,
26,
27].
The proportions of soft and hard segments within the SMP can be varied to tailor the thermomechanical properties of the material, such as the glass transition temperature, allowing the SME exhibited by the structure to be changed [
18]. By mixing the resins which make up the polymer in different proportions, the visco-elastic properties of the polymer can be varied. For example, at temperatures above T
g an SMP will become compliant and rubbery due to increased molecular mobility of polymer chain concentrations of soft component monomer. Conversely, a rigid structure is produced at temperatures below T
g due to the restricted coiled state of the molecular chains in polymer increased concentrations of the hard component [
53]. Teoh et al. report that a higher T
g increases the response time of a thermally-actuated SMP [
18]. The study exploited this characteristic to achieve sequential/hierarchical response of a 4D printed structure by printing SMPs of varying glass transition temperatures. SMPs can be actuated by various mechanisms, including direct or joule heating (where electric current is passed through a conductor to release heat [
53], light, moisture, pH or radiation, amongst others. However, the majority can be categorised as either thermo-, photo-, or chemo-responsive [
11,
53]. The most widely researched and applied group of SMPs are thermally-actuated; those which change form or function upon heating as they exhibit a variety of mechanical, thermal, and optical characteristics [
19,
54]. Thermo-response materials can be attractive for biomedical use if they can be tuned to respond to the temperature within the body. Mu et al. consider SMPs to offer a wide range of actuation mechanisms [
52]. However, Pilate et al. suggest their resistance to electrical, light, and electromagnetic stimuli as a major disadvantage and limitation to their use [
11].
SMPs provide various advantages compared to inorganic ceramics and metallic smart materials, including low density, simpler processing, chemical stability, high stress tolerance, and high recoverable strains [
27]. SMPs can be fabricated to be transparent and are relatively inexpensive to produce compared to SMAs [
11,
51]. Their biodegradability, biocompatibility, and adjustable degradation rate make them particularly suitable for use in biomedical applications such as drug delivery systems (DDS) [
11]. Their low melting points (and hence increased printability) and inexpensive manufacture have encouraged their use within AM processes compared with alternative materials [
18]. 4D printing SMPs can achieve much faster printing speeds and higher structure stiffness than printed hydrogels [
20]. The use of poly (ethylene glycol) (PEG) in tissue engineering applications has been widely reported [
34,
55]. PEG is a water-responsive polymer, so it can be employed where moisture-responsive actuation is required. For example, Yang et al. produced a two-way body temperature-responsive and one-way moisture responsive PEG with the potential to actuate in response to the temperature and moisture levels within the body [
55]. Various researchers have criticised this material for having low thermal conductivity, exhibiting slow response speeds, and the requirement of low-temperature environments [
11,
51]. Their low tensile strength and stiffness also seem to restrict the use when firm structures are required [
11]. SMPs are promising smart materials for fabricating biomedical devices, and research should continue in this field to develop their potential.
3.1.2. Multi-Shape Memory Effect (Multi-SME)
Additive manufacturing provides an alternative for encoding the SME into SMP structures from traditional methods of hot and cold programming [
43]. Hot and cold programming mechanisms can be integrated within the 4D printing process to produce SMP structures that exhibit the triple-SME [
43]. Multi-SME exhibiting SMPs are structures with the ability to form more than one temporary form and sequentially recover from the temporary shapes in response to variations in the applied stimulus to return to their original form [
45]. This requires the presence of multiple reversible transition points and can be achieved either by employing a polymer network comprising of multiple SMPs with different initiation temperatures or using one SMP with a wide-spanning initiation temperature. Triple-SMPs, which have two temporary forms, can achieve more complex shape-changing demands than dual-SMPs, which only deform into one temporary shape [
43,
56].
Mao et al. produced a thermally actuated self-folding object by 3D printing digital SMPs to form hinges in the structure when subject to temperature change [
57]. The self-folding response was achieved by using materials with different glass transition temperatures, T
g. This altered the thermo-mechanics within the structure and resulted in a hierarchical response upon varying the temperature [
57]. So-called digital materials have been widely used to produce sequential shape memory behaviour where multiple configurations are thermo-mechanically encoded into the structure [
56,
57]. Digital SMPs can be defined as composite materials comprised of multiple shape memory polymers with different SME initiation points (e.g., glass transition temperatures), resulting in sequential actuation of the structure in response to varying the stimulus (e.g., temperature).
Teoh et al. from the Singapore Centre for 3D Printing also performed research in this area and have printed a self-morphing orchid structure using SMPs of various glass transition temperatures to achieve hierarchical deformation in response to heat [
18]. This study achieved shape change of both individual components (local response) and the overall system (global response) induced by heating [
18]. Using different proportions of the materials VeroWhitePlus™ and TangoBlackPlus™ in each component resulted in varied glass transition temperatures and hierarchical self-folding of the orchid upon exposure to heat. Biomimetic hydrogel composites are discussed further in
Section 3.1.3 [
56]. Presently SMPs are used to make appliances, brackets, and occluders for biomedical applications [
52]. A recent development was made by Invernizzi et al., who were able to produce a thermally actuated 4D printed SMP with self-healing capabilities [
35]. This was the first study to report self-healing properties achieved in a 4D printed architecture, a desirable property for biomedical applications. The researchers concluded that the structures maintained their shape memory behaviour after healing and also highlighted their potential within the field of soft robotics [
35]. With further research and development in this field, the ability to manufacture dynamic, personalised structures that mimic natural tissues may be possible. The self-healing quality of polymers can be achieved by re-crosslinking through the polymer’s physical and chemical properties. Damage repair characteristics are achieved by doping the polymer with a healing agent [
52]. Self-healing and repair are a major research focus particularly in the field of tissue engineering.
3.1.3. Hydrogels
A hydrogel is formed of cross-linking polymer chains made from hydrophilic monomers. The chains are arranged in a three-dimensional network that gives hydrogels their ability to absorb large volumes of water without dissolving. This makes them differ from dry-state polymers as they expand significantly upon absorbing the water and can revert to their original size when dried [
58]. They were first developed by Wichterle and Lim in the 1950s, who synthesised a water-responsive polymer gel by crosslinking poly-hydroxyethyl methacrylate (PHEMA) with ethylene dimethacrylate [
59]. Due to their biocompatibility, hydrogels are commonly used in the manufacture of contact lenses, wound dressings, nappies, and drug delivery systems [
59]. Their 3D network structure and ability to swell with water provide conditions similar to those within the extracellular matrix [
19]. This, along with their biomimetic nature and moisture-driven shape transformation, makes hydrogels suitable for various other biomedical applications such as producing structures that imitate cellular environments and replacing or improving tissues within the body [
60]. Consequently, hydrogels are a popular area of material science research and are now one of the principle polymers used in 4D printing alongside SMPs [
20].
On their own, hydrogels are considered as being poor printing materials due to their soft nature, low Young’s modulus (generally limited at a few hundred kPa [
49]), and linear shape transformation restricting their use in biomedical devices [
37]. The response period for these structures is also relatively long, particularly for large architectures, due to the swelling mechanism relying on diffusion transport. A reversible actuation cycle of 10 to 20 h was reported by Mao et al. [
49]. As such, they are often combined with other materials such as non-swellable, stiff shape-memory polymers, or filaments to create hydrogel composite materials that display complex shape-morphing capabilities with increased stiffness [
20,
49]. The water-absorbing hydrogel can be printed alongside dry-state polymers to form hinged or jointed structures. This creates differential strains in the structure, the hydrogel swelling but the non-absorbent polymer maintaining its original form, resulting in an overall change in the configuration when immersed in water due to localised swelling [
20]. This technique produces a structure that, after printing, does not require further processing to achieve the desired shape change.
The use of hydrogel composites within 4D printing processes has been explored in several clear successes to create dynamic biocompatible structures. Ding et al., for example, displayed the ability to print a thermo-responsive hydrogel composite with an inherent SME [
20]. To the best of the authors’ knowledge, this study was the first to propose an alternative AM technique that embeds the shape memory behaviour into the structure while it is being printed. This compares with traditional methods of thermo-mechanic training after printing or creating differential strains by printing a combination of active and inactive materials. Controlling the photopolymerisation during printing allowed the construction of high-resolution structures with embedded controllable strains [
20].
The typical shape-memory programming of SMPs described in
Section 3.1.1 involves a 6-stage process where the printed structure transitions temporarily to the second configuration and returns to the original printed shape by varying the stimulus. In contrast, Ding et al. produced a structure that, once printed, deformed into a new permanent shape that would not return to its printed configuration [
20]. The shape change was onset by heat and the resultant configuration remained relatively stable when subject to varying temperatures, as illustrated in
Figure 8.
They also discovered that the multi-SME could be achieved through further thermomechanical loading of the structure. Multiple temporary shapes were coded into the material, and the structure continuously returned to its new permanent configuration [
20]. Gladman et al. have reported successes in 3D printing a biomimetic hydrogel composite ink that displayed localised and anisotropic swelling when immersed in water. In this study, stiff cellulose fibrils were embedded within an acrylamide matrix to create a composite ink that could mimic the shape-changing characteristics inherent in the cell wall of plants [
7]. The polymer was crosslinked by UV photopolymerisation. Controlling the shear alignment of the fibrils during the direct ink writing process created anisotropic swelling within the matrix resulting in complex, controllable shape-morphing capabilities. Manipulation of the swelling response was achieved by changing the direction of the printing path during the extrusion of the material. Precise, controllable folding of a 3D printed flower structure was achieved following water-actuation for two structures with different bilayer directions [
45].
Similarly, Huang et al. digitally printed a hydrogel composite, where they achieved complex and precise shape-change by tailoring the localised swelling. This was implemented by using precise control of the light exposure time rather than varying the printing path direction [
2]. Mao et al. used PolyJet technology to create a self-folding hydrogel SMC. They used a hydrogel bound by SMP and elastomer layers to form the composite used to fabricate a structure with reversible shape-transformation capabilities. The material performed autonomous folding upon immersion in low, followed by high-temperature water. The structure unfolded and returned to its original shape when immersed in hot water [
49].
Hydrogels can only be actuated within water or moisture-based environments, therefore, their use is limited in dry conditions. While this may be considered as a disadvantage for certain applications, this is seen as an advantage for biomedical applications as the hydrogels can be tuned to shape-morph in response to moisture within the human body [
18]. These early successes indicate a seemingly unlimited potential for the use of swellable hydrogel composites to fabricate biomedical devices. With further development in the issues of printability and response-cycle times, it seems that a future where medical devices are 4D printed using these smart materials is not so far away.