What are hydrogels?
Hydrogels are becoming the bread-and-butter of the Biomaterials world, especially when it comes to developing safe and effective treatments for life-threatening diseases. Hydrogels are essentially 3-dimensional structures that hold a lot of water (to put it in very scientific terms), and the simplicity of the structure is what lends to their versatility. They have the ability to respond to both environmental and biological stimuli by swelling, shrinking, or a variety of other modifiable functions. Common environmental stimuli could be changes in pH, temperature, or ionic strength; common biological stimuli could be the presence of glucose, certain proteins, or nucleic acid.
Hydrogels are specifically good for long-term treatment options because they have the ability to embed biologically active agents within them and allow their slow release into the body. The mechanical properties of hydrogels are similar to that of soft tissue, allowing for seamless implantation with little resistance. The soft nature also limits the inflammatory response from the surrounding area. Changing the hydrogel’s pore size can modify the drug’s release amount and release duration. If the drug molecule size is less than the pore size, there will be a rapid release of the drug, whereas if the molecule size is greater than the pore size, the drug is trapped in the gel and release is dependent on the deterioration of the gel. If the molecule size is equal to the pore size, there will be a slow release of the drug. Overall, the treatment approach of implanting a “drug reservoir” at the targeted site and allowing for the slow release of the drug offers numerous benefits. Namely, there will be fewer drug administrations, there will be less enzymatic degradation of the drug, and it will allow for a higher concentration in a specific area for a longer time (as opposed to injecting a high concentration and it dispersing immediately).
Enhancements to hydrogels that improve their function
As hydrogels become mainstream in the biomaterials world, various enhancements have been made to add specific functions which basic hydrogels don’t have. The following types are a small glimpse of the many variations of hydrogels that exist.
Cross-linked hydrogels are a common variety where multiple different formations of hydrogel are layered on top of one another to create a denser gel. This process essentially combines multiple loose networks, with big pores, to create a net with smaller pores, thereby increasing mechanical strength and flexibility. This also allows the absorption of water and bioactive compounds, without the gel falling apart, opening up a host of new functions and opportunities.
In-situ forming hydrogels are injected as a liquid and can jellify in response to environmental stimuli. This stimulus can be as simple as a change in temperature, which will evidently occur when the gel is being moved from storage to inside the body. Traditional hydrogels, which are created as a gel and implanted into the body, are referred to as performed hydrogels. In-situ hydrogels don’t require any surgery as long as the site is at an injectible location. This drastically reduces both the recovery time and cost for the patient.
Nanogels are nanoscopic hydrogels that can be injected into blood or tissue. They have similar modifiable properties to macrogels (porosity, size, degradability, stimuli responses, etc.). They can transport and release drug molecules in response to stimuli or degradation of the gel. They are intravenously injected and have the ability to travel inside cells and deliver the nanoscopic drug molecules. From there, the drug can complete its normal function, whether that might be releasing a signal or inhibiting certain proteins. Due to their size, nanogels have the advantage of accessing areas of the body that are inaccessible to macrogels. Additionally, they enhance drug stability and enable targeted drug delivery.
Hydrogels in treatment!
In 1961, Otto Wichterle and Drahoslav Lím first employed hydrogels in a medical context by developing soft contact lenses. Hydrogels now offer more than just structural support; their ability to encapsulate and release bioactive compounds on demand is highly beneficial. The medical world has realized this, and hydrogels are becoming increasingly popular as treatment options for serious diseases. The following examples are only a small slice of the huge variety of uses for hydrogels.
CAR T-cell treatments (I talked about more in-depth here) are genetically engineered T-cells that are implanted in the body, using a hydrogel, and are able to slowly eat away at a tumor. The hydrogel plays a crucial role in the treatment by creating a suitable environment for the T-cells to proliferate and become activated. Some versions have even been developed to include stimulating cytokines in the hydrogel to promote immune activity. The release rate can be engineered for the amount of time and whether release is dependent on a stimulus or degradation of the gel.
Hydrogels can also be used in nucleic acid delivery, whether that may be for a vaccine or treatment for a disease. They enable sustained release, allowing for a lower dose over an extended duration, instead of a high concentration that rapidly dissipates in the bloodstream if administered via injection. They can also be designed to release nucleic acid once the gel degrades to a predetermined level, eliminating the need for multiple vaccine doses. Hydrogel vaccines could be mass-produced, as they don’t need to be specified to the patient, and would increase accessibility for crucial vaccines such as COVID-19 and Flu.
Another new idea in the works is using hydrogels to employ targeted chemo and radiation therapy. This could drastically reduce the toxic effects these taxing treatments take on the body. Hydrogel chemotherapy could also recruit and activate immune cells to combat the hostile anti-immune microenvironment, which could enhance the effectiveness of the treatment and minimize its impact on the patient. Similarly, the hydrogel model could be applied to immunomodulation after the main cancer treatment is over. Therapies, like hormonal treatment, modulate the patient’s hormones with the goal of preventing another tumor from developing. Instead of taking a pill every day, a hydrogel could be injected/implanted to the affected site and slow-release the drug; this method allows for more control in the hands of the doctor as they can program the gel for release amounts, duration, and frequency. Lastly, a cancer vaccine could be developed to stoke the immune response to specific cancers, preparing patients who are known to be high risk. While there is still a great deal of research required to develop an effective cancer vaccine, hydrogels present a promising vehicle for administering the vaccine once viable antigens have been identified. By allowing the drug to be released over a longer period of time, the immune system would have the time to retain how to respond to that cancer (without the need for a second dose), making the possibility of a cancer vaccine a momentous advancement.
The future of hydrogels and beyond!
Hydrogels have a unique versatility that allows them to transform vastly different treatments, having an effect across the whole medical field. Their future looks bright, as they offer several advantages over other materials, such as biocompatibility, tunable properties, and ease of processing. Overall, I can’t wait to see the pioneering treatments researchers develop with the ever-improving hydrogel technology; hydrogels will change the way we approach treatments and patient experience forever.
Works Cited
Buwalda, Sytze J., et al. “Hydrogels for Therapeutic Delivery: Current Developments and Future Directions.” Biomacromolecules, vol. 18, no. 2, 10 Jan. 2017, pp. 316-30, https://doi.org/10.1021/acs.biomac.6b01604.
Correa, Santiago, et al. “Translational Applications of Hydrogels.” Chemical Reviews, vol. 121, no. 18, 3 May 2021, pp. 11385-457, https://doi.org/10.1021/acs.chemrev.0c01177.
Parhi, Rabinarayan. “Cross-Linked Hydrogel for Pharmaceutical Applications: A Review.” Advanced Pharmaceutical Bulletin, vol. 7, no. 4, 31 Dec. 2017, pp. 515-30, https://doi.org/10.15171/apb.2017.064.
Peppas, N.A., and B.V. Slaughter. “Hydrogels.” Polymer Science: A Comprehensive Reference, Elsevier, 6 June 2012, https://www.sciencedirect.com/science/article/abs/pii/B9780444533494002260.
