Green and Affordable: Bring Medical Nanomaterial to the People

Nanofibers made of cheap but sustainable nanoparticles can have limitless medical applications


Nanomaterial (Source: Dr. Lucy Vojtová)



Unfortunately, sometimes accidents even happen to the most cautious people. 

Now, this can be upsetting, but please close your eyes and imagine: what if your skin is burnt severely? Or if your bones are fractured due to a car crash? What do you need? Perhaps a low-cost, non-toxic, user-friendly drug delivery material (e.g., medicine-infused transdermal patches)? Is this even possible?

By studying nanomaterials, Dr. Lucy Vojtová, a material chemist at CEITEC BUT, along with her fellow researchers, is proceeding to make this dream a reality 1, 2.



What is Nanomaterial?


Nanomaterials are made of nano-sized particles of which one or more dimensions is in the size range 1 nm - 100 nm: visualize creating a piece of cloth, but replacing the visible textiles such as satin and silk with materials measured in nanometers (1 mm = 1000000 nm).

Not only are the pores in between the materials so tiny that even bacteria and water molecules cannot pass through, but the surface area is amplified for absorbing more compounds such as drugs, making nanomaterials ideal for drug delivery 3, 4.



Nano Problems


Now you might think “Nanoparticles sound wonderful! Surely there is no downside, right?” Unfortunately, nanoparticles can damage the human body depending on factors such as size, chemical composition, and concentration 5, 6, 7, 8.

For example, gold nanoparticles in high concentration can be toxic or insoluble; poly(amidoamine) nanoparticles can kill human lung cells by passing through the cell membrane with ease; inhaling nickel nanoparticles are likely to induce lung inflammation.

In addition, with so much emphasis on improving the medicinal properties at all cost, scientists sometimes overlook the market price of the nanomaterials 7. Expensive raw materials and the complex manufacturing processes are rendering the nanomaterials to be unaffordable for patients from less wealthy backgrounds or underdeveloped countries.

However, there are way outs!


....



Doing the Impossible


Dr. Vojtová and her fellow researchers believe they can overcome such obstacles. “Our goal is to develop an absorbable, non-toxic, low-cost, tissue-like substrate that can promote the regeneration of tissues.



Dr. Lucy Vojtová



Using electrospinning, a mass production method of nanomaterial, the researchers invented biocompatible and non-toxic nanofibers by blending a biodegradable polymer combining synthetic polycaprolactone (PCL) and natural gelatin (Gel) 2.

PCL is not only stiff and long-lasting but also hydrophobic, meaning it is repulsive to water. So, instead of getting wet, fluids such as blood, urine, and sweats slide off the surface, helping to cover and maintain the hygiene of wounds.

Meanwhile, the Gel is hydrophilic, making it water-absorbable. Applying gel on skin irritations, such as burnt skins, can reduce discomforts and chances of tissue damages caused by friction from external contacts 9.

By combining PCL and Gel, these nanofibers have both traits, and the composition of the nanofibers can be adjusted depending on the requirement.

Can you imagine a patch for burnt skin that is easy to put on and peel off, with a protective PCL outer layer, and a drug-inserted absorbable Gel underneath? Or perhaps bone scaffolds stuffed with drug-infused resorbable nanofibers, which are comfortable and does not require removal?

All can be achieved!



Imagine a bone scaffold stuffed with drug-infused resorbable nanofibers? It can be achieved! 




Halloysite Nanotubes


Dr. Vojtová and her former PhD student Dr. Pavliňáková, along with their collaborators from Brno University of Technology, Masaryk University, and Slovak University of Technology in Bratislava have also been finding ways to improve the PCL/Gel nanofibers - and they found the answer in halloysite nanotubes (HNTs) 2.

HNTs are a type of inorganic, natural, non-toxic, tube-shaped nanoparticles from the aluminosilicate clay mineral, halloysite.



HNTs are reinforcing the nanofibers (Source: Dr. Lucy Vojtová)



HNTs yield excellent results in reinforcing both mechanical and biological properties of the nanofibers: by incorporating just 0.5% of HNTs into one nanofiber mesh (30mm x 5mm), its elasticity and tensile strength, doubled, and its elongation increases drastically by 4 times. The pore-size also shrinks significantly with the addition of HNTs, ensuring a compacted texture with improved water molecules blockage, and a larger surface area for drug carriage.


Most promisingly, these nanofibers (with or without HNT) are exclusively biocompatible featuring their nontoxicity to mouse fibroblasts cells (a fundamental type of cells in mammalian connective tissues), a significant outcome of this study.


Connective tissues, such as fat, bone, bone marrow and the inner layer of skin, are abundant in the human body. They serve as the glue that holds all body parts together. Not only supporting and connecting but also transporting essential substances (e.g., oxygen and glucose) throughout our body.


Fibroblasts synthesize collagen, which gives strength, structure, and cushioning to the connective tissues- necessary procedures for a damage connective tissue to recover 10, 11, 12. Therefore, nontoxic nanofibers are not only useful for healing injuries but might also reduce animal testing; drugs can be first tested on cells growing on these nanofibers, instead of living animals.


Besides the benefits mentioned above, HNTs can also allow more drug to be incorporated into the nanofibers. Since HNTs are tube-shaped, with the outer surface made of silica, and the inner surface made of aluminum oxide, different drugs can be loaded into corresponding parts based on their chemical composition. “However, we have not tested any drugs on the HNTs yet. That’s our next step,” states Dr. Vojtová.




Bring the Future to the People



With or without HNTs, the potentials of these nanofibers


are limitless.


Dr. Vojtová’s team has taken steps forward to make nanofibers even beneficial. "We have a Czech patent for Gel nanofibers modified with antibacterial and hemostatic oxidized cellulose 1, 13, 14,"

Dr. Vojtová proclaims proudly, "and we are exploring all its possible applications."

For example, collaborations with the Department of Burns and Plastic Surgery, University Hospital Brno for developing full-thickness skin-regenerating products for burn victims and plastic surgery patients are already on-going.


Another project with the Trauma Surgery Department, University Hospital Brno aims to invent a type of biopolymer nanofiber-incorporated ceramic spinal disc placed in between the vertebrae, which may be able to help people suffering from the painful degenerated disc disease.


Speaking of bones, novel composite scaffolds surface-modified with nanofibers are being tested in-vivo for large femoral bone defect regeneration under the collaboration with CEITEC Veterinary and Pharmaceutical University Brno. The researchers together with orthopedics from Motol University Hospital in Prague also envision a type of “bone-glue”: an injectible nanofiber- based glue filling the space between cracked bones, providing more comfort and flexibility, which can substitute the painful application of surgical bone-screws.

In all cases, Dr. Vojtová is cooperating with key players both from academic and industrial spheres (from the Czech Republic and beyond), striving to reach these tangible outcomes.



"Bone-glue": an injectible nanofiber- based glue filling the space between cracked bones



Lastly, Dr. Vojtová and co. hope to replace synthetic PCL, the priciest of all materials for these nanofibers, with cheaper and bioactive natural resins. This will make the nanofibers more affordable, allowing patients with skin defects to change the healing materials less frequently - a more convenient practice.

Lower cost can also open doors to markets in developing countries that couldn't enjoy the benefits of high-cost medical nanomaterials. Material scientists should not only focus on improving the medicinal properties of the nanomaterials, but also on making them more affordable and less hazardous” Dr. Vojtová passionately exclaims her principles.


After all, progresses in science should not burden the already-suffering patients, but offer them a better life.



References

  1. Švachková, Veronika, Lucy Vojtová, David Pavliňak, Libor Vojtek, Veronika Sedlákova, Pavel Hypšl, Milan Alerti, Josef Jaroš, Aleš Hampl and Josef Jančář. (2016). Novel electrospun gelatin/oxycellulose nanofibers as a suitable platform for lung disease modeling. Materials science and engineering: C, 67, 493-501. Doi: 10.1016/j.msec.2016.05.059.
  2. Pavliňáková, V., Fohlerová, Z., Pavliňák, D., Khunová, V., & Vojtová, L. (2018). Effect of halloysite nanotube structure on physical, chemical, structural and biological properties of elastic polycaprolactone/gelatin nanofibers for wound healing applications. Materials Science And Engineering: C, 91, 94-102. doi: 10.1016/j.msec.2018.05.033
  3. Mukherjee, B., Dey, N., Maji, R., Bhowmik, P., Das, P., & Paul, P. (2014). Current Status and Future Scope for Nanomaterials in Drug Delivery. Application Of Nanotechnology In Drug Delivery. doi: 10.5772/58450
  4. Sharma, K. (2017). Nanomaterials for Drug Delivery. Advances In Personalized Nanotherapeutics, 57-77. doi: 10.1007/978-3-319-63633-7_5
  5. De Jong, W. H., & Borm, P. J. (2008). Drug delivery and nanoparticles:applications and hazards. International journal of nanomedicine, 3(2), 133-49.
  6. Oxford University Press. (2009, June 11). Health Risks Of Nanotechnology: How Nanoparticles Can Cause Lung Damage, And How The Damage Can Be Blocked. ScienceDaily. Retrieved January 11, 2019 from www.sciencedaily.com/releases/2009/06/090610192431.htm
  7. Nanoparticles as a Drug Delivery System. Retrieved from https://www.medscape.com/viewarticle/770397_5
  8. What are potential harmful effects of nanoparticles?. (2007). Retrieved from http://ec.europa.eu/health/scientific_committees/opinions_layman/en/nanotechnologies/l-3/6-health-effects-nanoparticles.htm#4p0
  9. Group, T. (2017). Advances in Hydrophilic and Hydrophobic Coatings for Medical Devices - Tech Briefs :: Medical Design Briefs. Retrieved from https://www.medicaldesignbriefs.com/component/content/article/mdb/features/articles/27725?Itemid=684
  10. Saladin, K. Connective Tissue - Biology Encyclopedia - cells, body, function, human, animal, system, organs, blood, types. Retrieved from http://www.biologyreference.com/Ce-Co/Connective-Tissue.html
  11. McDougal, W. What Is Collagen? - Definition, Types and Diseases [Video]. Retrieved from https://study.com/academy/lesson/what-is-collagen-definition-types-and-diseases.html
  12. McDougal, W. Connective Tissue: Types, Functions & Disorders [Video]. Retrieved from https://study.com/academy/lesson/connective-tissue-types-functions-disorders.html
  13. Composition for the preparation of modified gelatinous nanofibers and nanofibers, Veronika Švachková, David Pavliňak, Milan Alberti, Pavel Hypšl, Lucy Vojtová and Josef  Jančář in Utility model, registration number: 26811, Úřad průmyslového vlastnictví 2014.
  14. Composition for the preparation of modified gelatinous nanofibers, nanofibers per se and process for preparing thereof, Veronika Švachková, David Pavliňak, Milan Alberti, Pavel Hypšl, Lucy Vojtová and Josef  Jančář in Czech patent, registration number: 306258, Úřad průmyslového vlastnictví 2016.



Written by Sophia Man 

Edited by Somsuvro Basu 


Publication date: 29.03.2019