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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. 

Introduction

Advancements in computational methods are becoming increasingly more essential to innovation within medical research and development. Quantum computers are being developed as revolutionary machines that leverage quantum bits, or qubits, which can exist in a unique state called superposition. This means qubits can represent both 0 and 1 simultaneously, unlike classical bits, which are limited to being either 0 or 1. Qubits allow quantum computers to perform complex computations at speeds and precision levels that traditional supercomputers cannot match.  Quantum computing will  serve as a possible avenue of improvement in drug-development processes to keep making progress in treating unmet medical needs.

Computer-aided drug design 

Many chemists are currently focusing on discovering and developing quantum computing algorithms to solve complex electronic structures of atoms with strong electron correlations—problems that are challenging for classical computers to handle accurately. Quantum computers offer a significant advantage in these calculations, especially for applications like computer-aided drug design.

In the pharmaceutical sector drug design is a lengthy process, as chemical compounds take time to  identify and develop. Thus, the primary objective of obtaining clinical compounds is to have the  fewest number of refinement cycles possible. This process begins by identifying a target compound (such as protein), which causes disease, and then screening millions of chemicals for their ability to bind to and neutralize it. The Molecule candidate will then enter the clinical development phase after testing tens of thousands of possible molecules in vitro for biochemical, biophysical, and biological properties.

Due to the prolonged timeline in drug design, computational methods can help in the development of appropriate molecules by offering insights and assistance on drug design to produce safer and more effective medications. It can calculate more accurately the electronic structures of molecules, which makes it possible to determine the binding strength and affinity of compounds using electronic structure methods, as well as can predict pharmacokinetic properties, which are used in how compounds are absorbed, distributed, metabolized, and excreted from the body.

Quantum-computational simulations in drug design would gain the most from creating efficient algorithms that can speed up the process and result in far better models of molecular interactions. Current methods provide high accuracy for the key systems, yet are too slow for common use in drug development. 

Discussion

In the near future, quantum computing may prove to be useful for certain quantum chemical computations. However, it is too early a phase of research to correctly anticipate when the pharmaceutical sector will completely take advantage of every aspect of quantum computing for its various uses. As conventional quantum-chemistry methods are currently unable to adequately and reliably characterize quantum systems, more advancements in hardware and the creation of innovative algorithms will be essential in the coming years.

Introduction

Bioglass is an innovative biomaterial renowned for its bioactivity and ability to bond with bone and soft tissues. This class of bioactive materials, composed mainly of silica (SiO₂), calcium oxide (CaO), sodium oxide (Na₂O), and phosphorus pentoxide (P₂O₅), has seen significant advancements in recent years. Originally developed for bone regeneration, bioglass is now at the forefront of medical applications, including tissue engineering, antimicrobial coatings, and drug delivery systems. These advancements stem from cutting-edge research in surface modifications, composite materials, and functional coatings that enhance the properties and applications of bioglass in the biomedical field.

The Chemistry Behind Bioglass

The bioactivity of bioglass is rooted in its chemical composition and the reactions it undergoes upon exposure to physiological fluids. When a medical professional implants bioglass into the body, it undergoes a series of reactions starting with the leaching of sodium and calcium ions, which raises the pH, initiating the formation of a silica gel layer on the glass surface. This gel layer serves as a template for the nucleation of hydroxyapatite, the mineral phase of bone. Simultaneously, the release of calcium and phosphate ions into the surrounding tissue aids the deposition of new bone minerals, thus bridging the gap between the implant and the natural bone. Recent innovations have fine-tuned this process by introducing dopants like magnesium, strontium, and zinc. These dopants enhance the bioactive response, improve mechanical strength, and tailor the degradation rates to match tissue healing processes.

Surface-Modified Bioglass

Recent studies, such as those published in the Journal of Nanoparticle Research, have focused on enhancing the bioactivity of bioglass. By altering the surface chemistry, researchers have significantly improved the material’s antibacterial properties and its ability to promote angiogenesis ( the formation of new blood vessels, which is critical for tissue regeneration). Surface modifications, such as the incorporation of silver, copper, or zinc ions, make bioglass more effective in preventing infections in implanted materials. These ions disrupt bacterial cell walls, leading to cell death, while simultaneously promoting the formation of hydroxyapatite—one of the key components in bone mineralization. This dual function of bioglass is crucial in applications such as bone regeneration and wound healing.

Copper-Based Composites: Expanding the Horizons of Bioglass Applications

In addition to traditional applications, bioglass has found novel implementations in advanced electronic and biomedical devices through the development of copper-based composites. A study published in Nanoscale Advances revealed that incorporating nano-sized particles into copper matrices enhances the material’s mechanical strength, thermal stability, and electrical conductivity. These properties are crucial for next-generation electronic packaging and biomedical devices that demand both durability and high performance. The use of such composites is particularly promising for developing multifunctional implants and devices that require both bioactivity and robust mechanical properties​. The copper ions also play a role in angiogenesis, further supporting tissue regeneration.

Advanced Bioactive Glasses

The field of tissue engineering has benefited immensely from the development of novel advanced bioactive glasses. Recent breakthroughs involve the integration of elements such as strontium and boron into bioglass. Strontium ions mimic calcium ions and are readily incorporated into new bone tissue, where they not only enhance bone density but also slow bone resorption by inhibiting osteoclast activity. Boron, on the other hand, improves the glass’s solubility, allowing for more controlled degradation rates, which is essential for the gradual release of therapeutic ions. These additions not only enhance the material’s ability to regenerate bone but also improve its antibacterial activity. This dual functionality is essential for preventing infections and promoting the rapid healing of bone defects, making bioglass an increasingly attractive option for orthopedic and dental applications.

Functional Coatings and Hybrid Materials: Paving the Way for Next-Generation Implants

Bioglass is also being explored in combination with other materials to create hybrid systems that offer enhanced properties. For example, integrating bioglass with hydroxyapatite has led to improved osseointegration (the formation of a direct interface between an implant and bone, without intervening soft tissue) and mechanical strength. The hydroxyapatite layer mimics natural bone minerals, promoting the adhesion and proliferation of cells that form and heal bones (osteoblasts), while the bioglass beneath continues to release ions that support bone growth and fight infection. These hybrid materials are particularly useful in the development of long-lasting implants and prosthetics, where both bioactivity and mechanical integrity are crucial. The ongoing research in this area suggests that such multifunctional materials could revolutionize the design and functionality of future biomedical devices​.

Conclusion

The evolution of bioglass technology is a significant leap forward in biomedical science. The innovations in surface modifications, composite materials, and hybrid systems not only enhance the performance of bioglass in traditional applications but also expand its potential into new therapeutic areas. As research continues to advance the boundaries of what bioglass can achieve, it is poised to play a transformative role in regenerative medicine, tissue engineering, and beyond. The future of bioglass is bright, with its applications extending well beyond the realm of bone regeneration, into the development of smarter, more effective biomedical devices.

Introduction

Antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi, and parasites evolve to become drug-resistant, pushing antibiotics and other antimicrobial medicines to practical obsoletism and thus increasing the difficulty of infection treatment. The prevalence of AMR is a pressing issue, cited by the World Health Organization (WHO) as one of the top 10 global public health threats facing humanity.

A promising threat to AMR is the use of “phage therapy”, a method of utilizing bacteriophages (phages) to eliminate specific bacterial strains.

Phages are viruses of bacteria that evolve to be extremely specialized, targeting only their certain type of bacterial cells and not affecting human cells. This opens a door for phage therapy to be used within the human body against bacterial infections, rather than solely antibiotics.

In the 1940s, the Western world saw chemical-based small-molecule antibiotics usurp potential research into phage therapies. Continued research into the potential of phage therapy allowed members of the former USSR to harness bacteriophages to treat disease. Phage therapy is now commonplace in Eastern Europe, specifically in Russia and Georgia where it is offered over-the-counter.

Dependency upon antibiotics has resulted in a fight against antimicrobial resistance, however, phage therapy may just be the method to bring us out of it.

Advantages of Phage Therapy

Bacteriophages occur abundantly on Earth, from the water of the oceans to the human GI tract. To attack bacterial cells, phages initiate the lytic cycle, wherein they first puncture the bacterium and then inject their own genetic information. The cell becomes a metaphorical warehouse for new phages, producing and assembling phages until the cell is full. Phages within the cell release endolysin, an enzyme that signals the end of the lytic cycle and causes the bacterial cell to explode, releasing brand-new phages.

There are many advantages to employing phage therapy over traditional antibiotic approaches.

Bactericide:

Phages are bactericidal, meaning they kill their host bacteria. However, some antibiotics are only bacteriostatic and cause a bacterium to become stuck within its stationary phase of growth rather than killing it, leaving behind the viable cell and opening a pathway for potential AMR.

Dosage:

As phages undergo the lytic cycle they self-amplify in an exponential fashion, which could potentially allow for a phage therapy to be effective with single or very low dosages. Lingering in the body after infection is not a worry, as phages only continue to multiply as they are killing bacteria.

Flora Bacteria:

Normal flora bacteria, “good” bacteria of the body, do not generally fall into the extremely specific target ranges of phages, which means they are almost totally unaffected by their presence in the human body. When antibiotics are introduced into the body, however, they tend to wreak havoc on any bacterium they come into contact with, including the normal flora that inhabits our bodies and aids us in many everyday functions.

Resistance:

When bacteria develop resistance to a chemical-based antibiotic it resembles an en masse revolt against one “villain”. Yet, bacteria find it relatively more difficult to develop resistance against phages due to their specific host ranges, since there is no single “villain”. Additionally, as bacteria evolve against phages, the phages have the capability to evolve right along with them, protecting the body against any bacterial strains that develop resistance.

FDA Approval

While phage therapy seems a promising opportunity, the US Food and Drug Administration (FDA) agency has yet to approve any therapies. As phage therapies are classified as biological products by the FDA, any manufacturing needs to adhere to standards like GMP, preclinical research, and all stages of clinical trials. This approval process is a tedious effort, however, as of October 2023 the US has the most phage-related Industry-Sponsored Trials (ISTs) on the worldwide scale, showing there is significant industry-related innovation on this front. Some examples of promising phage therapies in clinical trials within the US include WPP-201 for chronic venous leg ulcers and PreforPro for gastrointestinal distress.

Some of these ISTs are in their third phase of clinical trials, wherein the phage therapies are being tested for large-scale efficiency and comparison to currently market-available competitors. This is the final stage of testing prior to a drug or treatment to be submitted to the FDA for approval.

Despite the many advantages of phage therapy, there is still room for major disadvantages that are avoided through thorough testing prior to FDA approval. Namely, phages possess a narrow host range, inherent biological nature, and unfamiliarity within traditional Western medicine. For these reasons, along with the lengthy approval process, there is still time to go before Americans see phage therapies available to them for treatment.

Although the 1940s saw a shift away from bacteriophage research within Western countries, as time progresses, they could still very well be our savior from the self-inflicted antimicrobial resistance crisis.