Categories
Biomedical Research

Bioglass: A New Frontier in Biomedical Applications

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.

Portrait of scientist looking under microscope in medical development laboratory, analyzing petri dish sample // freepik.com

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.

Resources

Abodunrin, O. D., Bricha, M., & El Mabrouk, K. (2024). Beyond bone: A systematic review on bioactive glass innovations and breakthroughs in skeletal muscle regeneration. Biomedical Materials & Devices. https://doi.org/10.1007/s44174-024-00220-1

Kaou, M. H., Furkó, M., Balázsi, K., & Balázsi, C. (2023). Advanced bioactive glasses: The newest achievements and breakthroughs in the area. Nanomaterials, 13(16), 2287. https://doi.org/10.3390/nano13162287

Taye, M. B., Ningsih, H. S., & Shih, S.-J. (2024). Exploring the advancements in surface-modified bioactive glass: Enhancing antibacterial activity, promoting angiogenesis, and modulating bioactivity. Journal of Nanoparticle Research, 26(2). https://doi.org/10.1007/s11051-024-05935-2Zhang, G., Zhen, C., Yang, J., Wang, J., Wang, S., Fang, Y., & Shang, P. (2024). Recent advances of nanoparticles on bone tissue engineering and bone cells. Nanoscale Advances, 6(8), 1957–1973. https://doi.org/10.1039/d3na00851g

Categories
Biomedical Research

How Bacteriophages Could Stop the Antimicrobial Resistance Crisis

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.

Phage viruses bind to a bacterial cell, injecting their genetic material. // Biophoto Associates/SPL

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.

References

Carroll-Portillo, A., & Lin, H. C. (2019). Bacteriophage and the innate immune system: Access and signaling. Microorganisms, 7(12), 625. https://doi.org/10.3390/microorganisms7120625

Durr, H. A., & Leipzig, N. D. (2023). Advancements in bacteriophage therapies and delivery for bacterial infection. Materials Advances, 4(5), 1249–1257. https://doi.org/10.1039/d2ma00980c

Furfaro, L. L., Payne, M. S., and Chang, B. J. (2018). Bacteriophage therapy: clinical trials and regulatory hurdles. Front. Cell. Infect. Microbiol. 8:376. doi: 10.3389/fcimb.2018.00376

Ledford, H. (2023, June 26). Why phage viruses could be the key to treating deadly infections – if they can be harnessed safely. Nature News. https://www.nature.com/articles/d41586-023-01982-2

Loc-Carrillo, C., & Abedon, S. T. (2011). Pros and cons of phage therapy. Bacteriophage, 1(2), 111–114. https://doi.org/10.4161/bact.1.2.14590

Strathdee, S. A., Hatfull, G. F., Mutalik, V. K., & Schooley, R. T. (2023). Phage therapy: From biological mechanisms to future directions. Cell, 186(1), 17–31. https://doi.org/10.1016/j.cell.2022.11.017

World Health Organization. (n.d.). Antimicrobial resistance. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

Yang, Q., Le, S., Zhu, T., & Wu, N. (2023, September 6). Regulations of phage therapy across the world. Frontiers. https://www.frontiersin.org/articles/10.3389/fmicb.2023.1250848/full#:~:text=While%20there%20is%20no%20FDA,clinical%20trial%20(Table%201).

Categories
Biomedical Research Genetics

First CRISPR-based Gene Therapy Could be Approved in 2023

CRISPR-based gene therapies have yet to be approved by the FDA, despite their relative affordability and ease when compared to traditional gene therapies. This may change in 2023, as CRISPR Therapeutics and Vertex Pharmaceuticals announced that their biologics licensing applications (BLAs) to the U.S. Food and Drug Administration (FDA) were completed, including a request for priority review, which would shorten the FDA’s traditional twelve-month review of the application to eight months. This timeline opens the possibility for the first CRISPR gene-edited therapy to be available for interstate commerce within the year.

Background

CRISPR/Cas9 complexes were initially discovered in the natural immune systems of bacteria to protect them from viral invaders. The CRISPR component is a sequence complementary to a specific “target” sequence in a patient’s genome. It is sometimes referred to as the Guide RNA, as it guides the entire complex to the place within the genome where editing will occur. The Cas9 enzyme is the protein commonly depicted as a pair of metaphorical scissors, as it cuts DNA to allow for the insertion/deletion of intended genetic material. In the medical field, CRISPR genetic editing can be harnessed to potentially edit the genomes of individuals affected by currently incurable genetic diseases.

The CRISPR/Cas9 complex binds to and cuts the target sequence. / Javier Zarracina via vox.com

CRISPR/Cas9 is much more accessible than other FDA-approved gene therapies, due to its relative affordability and ease of use. Yet the FDA has shown caution when it comes to its approval. Major limitations of CRISPR-based medicines include:

  • The potential for off-targeting, wherein the complex incorrectly recognizes and binds to a sequence similar to the target sequence.
  • The triggering of the body’s immune response by CRISPR/Cas9, as it originates from bacteria.
  • The multi-faceted ethical concerns that come with genetic editing.

Methods and results

Despite concerns, researchers with CRISPR Therapeutics and Vertex Pharmaceuticals are in the final stages of clinical trials and are up for FDA approval with their CRISPR/Cas9 therapy for genetic blood disorders, called exagamglogene autotemcel (exa-cel).

Patients with sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT) who are participating in these trials have stem cells collected from their own blood. These cells are then edited with CRISPR/Cas9 outside of the body. Once the edited cells are introduced back into the body the patients are treated in accordance with traditional hematopoietic stem cell transplant (HSCT) procedures to establish high levels of fetal hemoglobin (HbF) production. HbF is the protein that carries oxygen throughout the bloodstream during fetal development.

The addition of HbF to a patient with SCD allows for a reduction or potential elimination of vaso-occlusive crises, wherein sickled red blood cells block blood flow to specific tissues, depriving them of oxygen and triggering an extremely painful immune response.

Within patients with TDT, increased levels of HbF reduce or eliminate the life-long dependence on blood transfusions that come with the characteristic severe anemia of the disease.

A doctor drawing blood from a patient. / Nguyen Hiep via Unsplash.com

CRISPR Therapeutics and Vertex Pharmaceuticals are in stage III of clinical trials, assessing both adults and children with SCD/TDT. They presented the adult data from 75 patients (31 with SCD and 44 with TDT) at the European Hematology Association Congress in December 2022.

All of the 31 patients with severe SCD that had been experiencing recurrent vaso-occlusive crises saw an elimination of the crises at their follow-up after exa-cel infusion (follow-up ranging from 2.0 to 32.3 months).

Of the 44 blood-transfusion-dependent patients with TDT, 42 were transfusion-free after exa-cel infusion (follow-up ranging from 1.2 to 37.2 months) and two were at the 75% and 85% marks in transfusion-reduction.

These CRISPR-based therapies show solid potential to change the idea of “incurable” blood diseases.

This research supports the biologics licensing applications (BLA) of CRISPR Therapeutics and Vertex Pharmaceuticals. A BLA is a request to the FDA to introduce a biological product, in this case the exa-cel gene therapy, to the interstate market. Within the BLA, there is a request for Priority Review, which would shorten the FDA’s traditional twelve-month review of the application to eight months, potentially allowing for the first CRISPR gene therapy to be FDA-approved within 2023.

Although the exa-cel CRISPR gene therapy is not approved just yet, it is an exciting innovation for CRISPR research and patients affected by “incurable” genetic diseases.

References
  • Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y.-S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., Ho, T. W., Kattamis, A., Kernytsky, A., Lekstrom-Himes, J., Li, A. M., Locatelli, F., Mapara, M. Y., de Montalembert, M., Rondelli, D., … Corbacioglu, S. (2021). CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. New England Journal of Medicine, 384(3), 252–260. https://doi.org/10.1056/nejmoa2031054
  • Kingwell, K. (2023, April 3). First CRISPR therapy seeks landmark approval. Nature News. https://www.nature.com/articles/d41573-023-00050-8
  • Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013). Genome engineering using the CRISPR-cas9 system. Nature Protocols, 8(11), 2281–2308. https://doi.org/10.1038/nprot.2013.143
  • Vertex and CRISPR therapeutics complete submission of rolling biologics license applications (Blas) to the US FDA for exa-Cel for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. Vertex Pharmaceuticals. (2023, April 3). https://investors.vrtx.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-complete-submission-rolling
  • Vertex and CRISPR therapeutics present new data on more patients with longer follow-up treated with exagamglogene autotemcel (exa-cel) at the 2022 European Hematology Association (EHA) Congress. Vertex Pharmaceuticals. (2022, June 11). https://investors.vrtx.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-present-new-data-more-patients
Categories
Neurology

Social Media Use During Pandemic Linked to Increased Tic Severity in Adolescents with Tourette’s

A study being conducted at the University of Florida is investigating a correlation between the use of social media during the COVID-19 pandemic and a change in tic severity for adolescents with Tourette syndrome.

Background

Tourette syndrome is a type of tic syndrome often present at a young age even as early as 2 years old. Tics are sudden movements, jolts, or sounds that those with tic syndromes feel the urge or are compelled to do. Often times it is compared to the urge of a sneeze where the person will feel great discomfort if they do not perform the tic. That being said, tics have the urge to be suppressed but not without causing discomfort to the individual.

Often times, people confuse and associate Tourette’s syndrome with coprolalia. Coprolalia is a specific type of phonic or vocal tic in which people shout obscene language. This specific type of tic is very rare and only affects around 10% of those diagnosed with Tourette’s Syndrome.

Study

After analysis of a patient population of surveys completed by adolescent individuals (n=20) with ages ranging from 11 to 21 years old, the researchers found statistically significant data showing that social media use, and increased social media use during the pandemic, causes an increase in tic severity and frequency.

  • 90% reported using social media more frequently during the pandemic
  • 65% reported using social media for an average of 6 hours per day
  • 50% reported that social media negatively impacted their tics
  • 85% reported that their tic frequencies worsened during the pandemic

This study was recently highlighted by both the University of Florida and the American Academy of Neurology (AAN) for its findings related to the implications of the pandemic on the mental health of adolescents. The researchers plan to add new participants to the study to strengthen the data and gain new insights.

This research is important as it can help to identify possible stressors for those with tics and work towards providing relief from tic symptoms for those with Tourette’s.

This article is based on the following sources

– American Academy of Neurology. (2022, February 28). Study: Tic severity linked with social media use for teens during pandemichttps://www.aan.com/PressRoom/Home/PressRelease/4961
– Centers for Disease Control and Prevention. (2020, May 13). Five Things You May Not Know About Tourette Syndromehttps://www.cdc.gov/ncbddd/tourette/features/tourette-five-things.html
– Mayo Clinic. (2018, August 8). Tourette syndrome – Symptoms and causeshttps://www.mayoclinic.org/diseases-conditions/tourette-syndrome/symptoms-causes/syc-20350465
– Tourette Association of America. (2016, May 21). Understanding coprolalia: A misunderstood symptomhttps://tourette.org/resource/understanding-coprolalia/
– University of Florida News. (2022, March). Heavy social media use may be linked to increase in tic severityhttps://news.ufl.edu/2022/03/social-media-use-and-tic-severity/