Background
The development of biomaterials as a method of treatment in medicine has evolved in tandem with the evolution of biotechnology. Of the variety of biomaterials that are studied everyday, silk fibroin is amongst the most promising. Taken largely from silk cocoons of moths, silk fibroin is a protein that is known for its appealing properties such as controllable biodegradability, high mechanical strength and stability, elasticity, and biocompatibility; all of which make it the perfect candidate for drug delivery. It can be utilized in a variety of different forms ranging from solutions to gels.
Silk-based drug delivery offers unique benefits as silk can be processed at mild temperatures, pressures, and pHs–removing the need for extreme manufacturing conditions that could damage the drug that the carrier is meant to deliver. This characteristic is unlike most other polymer biomaterials and thus offers exciting new opportunities for the future of biomaterials in medicine.
How Hydrogels Are Formed
Of the various ways that silk fibroin can be administered, one of the most common is through a hydrogel. When incorporated into a solution and subjected to either sonication or electrogelation, silk fibroin forms gels that differ from typical gels and are better described as soft, slightly rigid, water-rich structures. These silk hydrogels are usually formed through physical or chemical crosslinking, hence why the methods of sonication and electrogelation work. The difference between the two methods is that when physical crosslinking is induced, silk molecules form non-covalent bonds, whereas when chemical crosslinking is induced, reactions are carried to form a special network. The existence of hydrogels is important because they have the ability to mimic body tissues, allowing for sustained and gradual drug release over time.
Silk Fibroin Real World Applications
Inhalable Drug Delivery
An innovative real-world application of silk fibroin in medicine is its potential use for pulmonary drug delivery. Currently, cisplatin (a first-line chemotherapy drug) is delivered intravenously, resulting in widespread distribution throughout the body, low lung bioavailability, and high accumulation in the kidneys, leading to nephrotoxicity and other severe side effects. Its short-lived cytotoxic effect also necessitates frequent dosing, increasing treatment costs and burden on healthcare systems.
As a versatile biomaterial, silk could be used as an alternative inhalable treatment, wherein the silk is broken down into particles that can then be spray dried or spray-freeze-dried and then delivered to the airways. When used to deliver cisplatin via inhalation, these micro-carriers preferentially target the lungs, enhancing therapeutic efficacy while minimizing systemic side effects.
Injectable Hydrogels
An additional hallmark of how silk fibroin can make medical treatments less invasive is the injectable hydrogel. As previously mentioned, the hydrogel is versatile, having the ability to be injected into the body, conform to defect spaces, and release therapeutics over extended periods. This is due to its diffusive properties, where silk particles can easily exit the water-heavy gel, as well as the fact that hydrogels are biodegradable and thus break down in the body slowly, continuously releasing the drugs it is carrying as it does so. A relevant biomedical application is that of the degenerated intervertebral disc, where damaged vertebrae discs can be treated with hydrogels in a less invasive manner than surgical alternatives, since injectable hydrogels can withstand complex loading and “fit” themselves precisely to their target sites.
Living Medicines
Beyond drug delivery, silk hydrogels are being explored for the safe and sustainable delivery of living medicines, such as engineered cells and viruses, contributing to their growing popularity.” The sustained release mechanisms of the hydrogel support living medicines by controlling the delivery rate, while the encapsulation provided by the silk hydrogel protects the living medicine. In the case of bacteria, the hydrogel encapsulation keeps orally administered bacteria viable as it passes through the harsh gastric environment of the stomach.
Self-regulating Hydrogels
Finally, the use of silk hydrogels continues to evolve as they are now being developed to respond to body signals like glucose levels. This could be a breakthrough in the future treatment of conditions like diabetes, since self-regulating hydrogels have been developed that administer insulin in a glucose-responsive way, acting as an artificial pancreas of sorts. This is possible because changes in glucose levels in the surrounding environment trigger a transformation in these hydrogels that results in the controlled release of insulin.
The Future of Silk-Based Therapies
Silk fibroin is poised to become a leading biomaterial of the future, thanks to its remarkable versatility and potential to address a wide range of diseases and medical conditions. However, to fully realize its promise, significant challenges must be overcome, particularly in achieving consistent production and scalable manufacturing. At present, producing standardized silk hydrogels in large quantities remains a major hurdle. If research does succeed in overcoming this, silk fibroin could very well expand into more narrow fields like neurology, where its slow degradation rate has made it a promising candidate for long-term therapeutics.
References
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Murab, S., Samal, J., Shrivastava, A., Ray, A. R., Pandit, A., & Ghosh, S. (2015). Glucosamine loaded injectable silk-in-silk integrated system modulate mechanical properties in bovine ex-vivo degenerated intervertebral disc model. Biomaterials, 55, 64–83. https://doi.org/10.1016/j.biomaterials.2015.03.032 Zhang, M., Ran, M., Xing, M., Li, X., Han, S., Ren, K., & Wang, Y. (2025). A fully biodegradable and self-regulating injectable silk fibroin hydrogel for glucose-responsive insulin delivery. Applied Materials Today, 44, 102700. https://doi.org/10.1016/j.apmt.2025.102700
Gloriana Valladares Lima
Gloriana is a Chemical Engineering student and undergraduate researcher at the University of Florida. She is passionate about biochemical engineering and science communication, with research experience in biomaterials with medical applications. In addition to engineering, she has an appreciation for writing and editing and aspires to make scientific information clear and accessible to diverse audiences.
