Additive Manufacturing of Hydrogels

Copyright © Jacobs School of Engineering, UC San Diego

Brace yourself for a journey into the realm of additive manufacturing (AM) of biomaterials—a technological leap that is reshaping the landscape of healthcare as we know it. Biomedical products are no longer constrained by traditional manufacturing methods such as injection molding and plastic joining. Additive manufacturing opens up doors for increased freedom of design, mass customization, waste minimization, and much more. However, the limitations of steep costs and lengthy fabrication times have yet to be addressed. Despite this, AM biomaterials are becoming increasingly popular, and specifically, many advancements are being made with AM hydrogels. Welcome to the era of additive manufacturing. 

Copyright © Jacobs School of Engineering, UC San Diego

3D printed hydrogels

Additive manufacturing (3d printing) is the process of building a product from the bottom up, constructing each superfine layer based on a digital model. The development of AM has been especially impactful in the medical industry, as it can achieve a high complexity and specificity without increasing costs or production time. There are two main types of 3d printing, both of which have different benefits and limitations. Fused deposition modeling (FDM) involves extruding a heated/melted material onto a build plate, layer by layer, and cooling it to create the final product. Stereolithography (SLA), on the other hand, uses a liquid photopolymer resin that is cured by a UV light upon extrusion, differing from FDM because each layer is solidified immediately. Therefore, SLA tends to have a greater fabrication accuracy and is capable of creating interior/exterior pore structures which can contribute to more complex applications. Nevertheless, whether the material is cooled or cured, pure 3D-printed products tend to have poor mechanical functions. To combat this, Matrix Polymer Products were developed, which reinforce the pure polymers with strengthening particles and fibers before printing. 

But talking about 3D printing isn’t what you’re here for, is it? A relatively recent, and exciting, development is the emergence of Additive Manufactured hydrogels. Despite the ability to 3D print hydrogels, the benefits are outnumbered by the challenges. Limitations such as the scarcity of printable inks, a lack of mechanical strength, and limited flexibility limit the applications and reduce their efficacy. Not to worry, 3D printing’s cooler cousin is here— 4D printing and smart hydrogels! 

Copyright © Wang et al.

4D printed hydrogels— the cooler cousin!

4D printing is quite similar to 3D printing, except that the fourth dimension entails a time-dependent component. When hydrogels can respond to environmental stimuli over time, a whole host of new applications are opened up. There are 3 basic requirements for 4D printing (in addition to the norms of 3D printing): materials with stimulus-response capabilities, specific response environments to trigger stimuli, and time for transformation results. 4D printing results in smart hydrogels which respond to changes in their environment. Hydrogels can even be engineered to incorporate both non-responsive and responsive gels; when subjected to stimuli, these hydrogels exhibit uneven swelling or shrinking and adopt a new shape. Yet, one of the few limitations is that once the hydrogel is transformed, it is unable to return to its original shape. That’s where SMP hydrogels come in! 

Building upon smart hydrogels, shape memory polymer (SMP) hydrogels are able to return to their original shape after being exposed to environmental stimuli. The implications for SMP hydrogels are expansive. For example, if used for drug delivery and implanted in the patient, the drug could be released only when needed (determined by certain environmental conditions). A hypothetical instance when SMP hydrogels could be useful is in diabetic patients who struggle with low insulin. The hydrogel could release more insulin when levels are low, but then revert back to its original shape to store insulin when it is not needed. However, there are some limitations. They have low sustainability in humid environments, leading to polymer degradation and bio-inaffinity. They also cannot fully replace soft hydrophilic materials, and require some sense of rigidity. Still, smart and SMP 4D-printed hydrogels present many opportunities for advancement in the biomedical field. In fact, here are some applications I believe could be most influential! 


Of course, drug delivery is a major focus when it comes to the development of hydrogels. 3D printed hydrogels allow you to control the structure/pore size (and therefore drug release amount) based on the saturation of water; however, 4D printed hydrogels allow the drug release amount to be controlled by pH, temperature, the presence of certain proteins, etc. This new technology also allows doctors to specify the drug release amount for each patient, making personalized treatment much more accessible. These factors have made smart hydrogels for drug delivery a hot topic in the drug synthesis industry. 

Copyright © El-Sherbiny et al.

4D hydrogels are finding another compelling application as scaffolds within the field of tissue engineering. Tissue engineering involves building tissue implants to aid cell growth in an injured/affected area. While traditional hydrogels are primarily valued for their mechanical properties, the advent of smart hydrogels introduces the potential to incorporate additional functionalities. These smart hydrogels can assist in promoting cell growth and integrating the gel with the surrounding microenvironment. These opportunities will be especially influential in the quest to improve organ transplantation or even artificial organs. 

Lastly, 4D hydrogels are also improving hydrogel actuators. The shrinking and swelling of traditional hydrogels allow them to perform mechanical work; however, 4D gels can be controlled by a plethora of stimuli, opening up a host of new applications. For example, biodegradable hydrogel actuators could be used in artificial muscles. This technology could greatly improve their range of functions and biocompatibility. 

4D hydrogels have emerged as remarkable and versatile; their ability to respond and adapt to environmental stimuli (plus their biocompatibility and tunable properties) open up exciting possibilities for advancements in many biomedical fields: namely drug delivery, tissue engineering, and biomedical actuators. As we delve deeper into the realm of 4D hydrogels, it is clear that we are witnessing a paradigm shift in materials science and engineering. Their remarkable capabilities can offer transformative solutions to longstanding challenges, and I am excited to see what the future holds!