Researchers from the Jagiellonian University have designed a material that could help refill bone cavities and at the same time serve as a carrier for osteoporosis medication. The invention could revolutionise the treatment of osteoporosis, since it could allow doctors to deliver drugs with strong side effects precisely where they are needed, reducing the need to rely on systemic drug administration.
A research team from the Jagiellonian University Faculty of Chemistry led by Prof. Maria Nowakowska has developed a multifunction material designed to improve osteoporosis treatments and fill small bone cavities. This new hydrogel is injected into cavities, where it hardens through the process of chemical crosslinking that happens at 37 degrees centigrade. Thanks to its structure and composition, the hydrogel permanently fuses to bone tissue and serves as scaffolding which allows new tissue to naturally form and fill cavities.
Researchers envision an additional function of their invention. The chemical composition of the hydrogel allows it to become a carrier for osteoporosis medication which can be applied directly to tissues affected by illness, which benefits the patients in two ways. Firstly, it reduces the need to rely on systemic drug administration, which have noticeable side effects. Secondly, the hydrogel may be used to apply significantly larger doses of medication precisely where they are required, increasing the effectiveness of therapy. Additionally, the hydrogel facilitates natural bone regrowth.
‘The components used in our hydrogel imitate the natural composition of bone tissue. It contains collagen, hyaluronic acid and chitosan, a polysaccharide with confirmed antibacterial, anti-inflammatory and analgesic properties. Moreover, it also contains a key inorganic component: silica particles decorated with hydroxyapatite, which play a number of key roles in the designed therapy. After the hydrogel in injected, its components are bound with covalent bonds. This means that it can be administered non-invasively. Additionally, it doesn’t undergo uncontrolled degradation’, said co-inventor Dr hab. Lewandowska-Łańcucka from the JU Faculty of Chemistry.
‘The hydroxyapatite used in the hydrogel is actually present in living organisms as the main inorganic building material of bone tissue, affecting its durability. It has the same purpose in our newly designed material. The mineral increases the density of the substance, which easily adheres to bone tissue after injection and serves as scaffolding for osteoblasts that rebuild the bone. But that’s just a small part of our innovation. The real breakthrough is our ability to bind sodium alendronate, a popular osteoporosis medication, with the hydrogel, resulting in a multifunctional material with therapeutic applications. Because of this, doctors will be able to inject it precisely where it is needed, after which it will be slowly released into the organism’, said Dr Adriana Gilarska, who worked on the hydrogel within the framework of her PhD thesis.
The research team has already completed its tests on humanised mice. The purpose of the tests was to prove the hydrogel’s broadly understood biocompatibility in vivo. The scientists demonstrated that the substance can be safely injected without any toxic effects. Additionally, they observed natural angiogenetic processes (i.e. emergence of capillaries) in places where the hydrogel was administered. This points to the possibility of using the material as scaffolding for bone tissue. The hydrogel itself degrades slowly, in a controlled way. At the end of the experiment, which lasted for 60 days, traces of hydrogel were still visible in places where it was injected. Furthermore, in vitro studies shown that sodium alendronate in the hydrogel is released into the organism gradually, increasing its effectiveness.
‘The first tests using cell lines and animal models show promising results. As of now, we’re planning to use the hydrogel in designing therapies for small bone cavities, mainly resulting from osteoporosis, but also those caused by injuries or surgery. The newly invented material should be of great interest to rheumatologists, orthopaedists, neurologists and dentists’, said Dr Gabriela Konopka-Cupiał, Director of the JU Centre for Technology Transfer CITTRU.
Further research is neededCurrently, the research team is looking for opportunities to work with investors that would fund further development of the hydrogel and the necessary clinical trials. The researchers do not exclude the possibility of indirect commercialisation through a spin-off company as well as carrying out more development work with funding from the National Centre for Research and Development or National Science Centre. The hydrogel still has to be tested on larger animals, checked for toxicity and fine-tuned to provide the best therapeutic results.
Exact dosage to be determinedThe developers of the hydrogel are presently working on modifying the silica it contains to increase its capabilities in combating osteoporosis in the future. ‘Thanks to the funding we received from the National Centre for Research and Development, we can still make advances in our technology. We’ve managed to synthesise functionalised mesoporous silica particles decorated with hydroxyapatite, which allows the hydrogel to bind with and absorb more of the osteoporosis medication. Our research shows that using this type of particles will not only increase the concentration of sodium alendronate near the affected tissue, but the porous structure of the hydrogel will slow its release into the organism. This means that in the future, doctors will be able to adapt both the strength and length of the treatment to specific patients, virtually eliminating all side effects of systemic drug administration’, said Dr hab. Joanna Lewandowska-Łańcucka.
Fewer side effects
Why is direct administration of osteoporosis drugs so important?
Sodium alendronate is a very effective way of treating osteoporosis. It works by binding with bone hydroxyapatites. The medicine hampers the activity of osteoclasts – cells that are responsible for bone degradation – without affecting osteoblasts, which build the bones. Because of this, it facilitates natural bone regeneration. In people suffering from osteoporosis, bone tissue undergoes systematic degradation, losing mass and becoming brittle. This, in turn, leads to the formation of cavities which increase the risk of injury or breaking. It can be remedied by decreasing the effectiveness of osteoclasts, increasing the effectiveness of osteoblasts, or both.
Sodium alendronate is useful in treating osteoporosis, but is currently administered systemically, and as such carries the risk of a number of harmful side effects. Systemic drug administration means that its concentration in affected tissue is never adequately high. Consequently, it needs to be administered following a strict regimen, a the treatment itself is usually long and often not that effective. That is why it is critical to find way for administering medication directly where it is needed. In an optimal scenario, it would be released gradually, increasing the effectiveness of the therapy. The material designed by JU researchers fits exactly that description. The invention is protected by Polish and international patents.Original text: www.nauka.uj.edu.pl