3D printing has produced some amazing results, but the objects it creates are limited by their rigidity. That is, 3D printed objects are stuck in one shape, preventing them from adapting to changing surroundings. On the other hand, 4D printed objects–the extra dimension being time–can change according to their environment, opening up an array of benefits for numerous industries, particularly medicine.

In fact, recent breakthroughs in the field of 4D printing have opened the door for more efficient delivery of drugs, less invasive stents, adaptable internal splints, and even replacement tissues and organs.

3D vs. 4D Printing

3D printing has given us cheap and easy to make prosthetic limbs, space ship parts created in space, prototype habitats for Mars, homes, among many other examples, including–and quite controversially–fully functional firearms.

3D printers work much like an inkjet printer, in that they put down a layer of ink in a specific pattern dictated by computer. However, 3D printers usually use plastic resins, build 3D objects by stacking multiple 2D layers, and are guided by computers. Therefore, a 3D printer can be fed a computer aided design (CAD) file with the specifications of the 3D object, and, within a relatively short time, it will produce it.

4D printing uses essentially the same process, although it uses metamaterials, which respond to stimuli, including water, heat, light, electric fields, and magnetic fields. When these are applied, the metamaterial can expand, shrink, bend, reconfigure, etc.

For example, researchers at the Lawrence Livermore National Laboratory created objects injected with ferromagnetic particles. This enables the researchers to control the object’s shape by placing it in and tweaking a magnetic field. In a recent paper, the researchers claim that “Modulating remotely applied magnetic fields results in rapid, reversible, and sizable changes.”

Another example is a hydrogel–a gel that contains water–created by a team at Rutgers University. This metamaterial can change its shape and rigidity based on the temperature, which dictates how much water it absorbs or releases. They claim that this enables them to “tune their plastic-like materials with heat, so they stay rigid when struck or become soft as a sponge to absorb shock.”

A team from the City University of Hong Kong combined polymers and ceramic nanoparticles to create a metamaterial that can stretch up to 3 times its initial length when heated. This metamaterial was then placed into lattice molds which allowed for joints in specific areas, in the end creating complex structures that can expand and shrink. The team claims to have created structures as complex as a detailed, miniature recreation of the Sydney Opera House.

Scientists from North Carolina State University created polymers that change their shape when exposed to light. That is, these polymers come in different colors and respond differently to different wavelengths of light, enabling them to create self-folding objects. In a recent paper, they claim “These color patterns can be designed to absorb only specific wavelengths of light (or to absorb differently at the same wavelength using color hues), thereby providing control of sheet folding with respect to time and space.”

Another team of researchers created a metamaterial by combing ethanol and silicone elastomer, which responds to electrical currents. When applied, the current causes the ethanol to undergo a phase change from liquid to gas, causing the whole metamaterial to expand. When the current is removed, the metamaterial shrinks to its original size.

This video demonstrates how metamaterials work with basic objects.

Therefore, with the above examples as well as many others, a 4D printed object can change its size and configuration under specific conditions to perform different functions when needed.

4D Containers For Drug Delivery

One of the biggest challenges of drug delivery is releasing the drug at the right time and in the right area of the body. 4D printed micro-containers offer a solution, as they can open when the correct stimuli is provided.

For example, in a paper published in the journal Nature, researchers demonstrate that it is possible to create micro-containers that open when subjected to temperatures above 32 degrees Celsius. At this point, pores in the container expand, releasing the drug inside. Depending on the size of the pores and the shape of the container, the amount of the drug being released can be regulated accordingly.

4D Stents

A stent is a small mesh tube that is placed in a passageway to help keep it open, such as in an artery to restore blood flow. While these have certainly saved lives, they come with two main challenges. First, they need to be customized for each patient, and, second, placing them in the body is invasive. Of course, both of these can be made easier with 4D printing.

In a 2016 paper, scientists claimed to be able to print custom tubes that can shrink and expand based on the temperature. Therefore, medical professionals can scan the problem area, create a 3D model, print a stent of a specific shape, and shrink the stent, making it less invasive to place. Once in place, the stent would expand, thus holding open the artery, duct, etc.

Moreover, this team of scientists found a way to create 4D stents that respond to magnetic fields, allowing them to use magnets to both position it and control its shape and size.

4D Internal Splints

Most people have seen or used a splint to support a broken bone, but, in some cases, patients need internal support, such as holding open a collapsed airway. Of course, in a case like this, the splint must change with expansion and contraction during breathing. Typical splints cannot adapt, but 4D splints have the ability to change according to the needs of the patient.

This was demonstrated on three infants who all suffered from tracheobronchomalacia (TBM), which is when the airway collapses when breathing. Medical professionals from the University of Michigan say that they printed custom airway supports that are able to respond to specific breathing patterns. They also claim that these splints can continue to be used as the patient grows, as they can “adjust to tissue growth through designed mechanical and degradation behaviors over time.” This means that they become more flexible as time passes, due to a designed break down of the material, allowing it to adapt to the children’s natural growth.

4D Tissues and Organs

Researchers have already successfully produced functional 3D printed tissues and organs, known as bioprinting. That is, they use bioinks, which are made of specific stem cells, in a similar fashion to plastic resin, in that they stack one layer after another, although some methods use molds. The stem cells are then encouraged to grow into their preprogrammed tissue or organ. Simple 3D printed tissues have been used in testing for years, but, in recent years, researchers have created corneas, a bladder, a kidney, and a heart. Just recently, a team from Brazil made great leaps towards a working liver.

While this is certainly amazing, these organs are not the real thing. For example, the creators of the heart claimed that the heart cells lacked the ability to simulate the same coordinated pumping action as a normal heart, although they were still able to contract somewhat. Likewise, creating other complex organs requires having materials that can change and respond accordingly to better mimic the “microarchitecture of ECM components and multiple cell types in sufficient resolution,” according to a recent paper.

Of course, this is where 4D printing comes in, yet 4D printed tissues and organs are still in their infancy. That is, researchers believe 4D printing is the inevitable next step in bioprinting, as it allows them to replicate a dynamic and complex organ. Research is continuing at an accelerating pace, especially because the world has a growing shortage of donor organs.

Therefore, with the above in mind, it might take a while before you get a fully functional organ, yet it might not be that long before you can get a number of other 4D medical treatments that could very well save your life.

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