Injectable hydrogel developed at Unicamp has the potential to treat joint injuries

Analgesics, anti-inflammatories, collagen, physiotherapy and even surgeries. Some people have tried everything and still experience joint pain. Osteoarthritis or arthritis is responsible for up to 40% of consultations in rheumatology outpatient clinics, according to the Brazilian Society of Rheumatology. The disease, characterized by the progressive degradation of cartilage, limits movement and reduces the quality of life of approximately 12 million Brazilians.

One hope for those suffering from this problem is an injectable solution that turns into a hydrogel – a material that absorbs a lot of water. Developed at the State University of Campinas (Unicamp), the technology has high innovation potential for the biomedical sector. The material, bioabsorbable and compatible with connective tissues, allows the repair of intervertebral discs and other joints at the site of the injury, playing a shock absorbing role, similar to that of cartilage, generating pain relief and improving mobility.

“In principle, it can be applied to any joint”, says the research coordinator, Marcelo Ganzarolli de Oliveira, who has been dedicated to the development of nitric oxide donor biomaterials for more than 20 years. A [JM1] Innovation Agency Inova Unicamp supported the patent application for the invention, filed with the National Institute of Industrial Property (INPI). The technology is in Unicamp's Patent Portfolio and can be licensed to companies that wish to bring biochemical innovations to the market.

The solution synthesized at the Institute of Chemistry (IQ-Unicamp) consists of a mixture of hyaluronic acid, gelatin and nanoparticles that donor nitric oxide, a gas that exerts beneficial actions on the body. "O áHyaluronic acid in combination with nitric oxide can partially recover cartilage tissue during the hydrogel's residence time in the joint. It is not a systemic action, it is localized”, comments Oliveira. “Nitric oxide is naturally generated by the body and, when released from the material, in appropriate concentrations, it can reduce local inflammation, contributing to tissue regeneration”, he adds.

Topical applications – directly to the skin – of these biomaterials have already demonstrated anti-inflammatory, vasodilatory, healing and antimicrobial action. The group receives funding from Fapesp through the thematic project “Absorbable and topical biomaterials for the localized release of nitric oxide”.

Chemical modification to form the hydrogel

The use of hyaluronic acid and gelatin is not new in the biomedical market, but the combination of these two components with nitric oxide donor nanoparticles in a single formulation is what makes the proposal original. “Nitric oxide is a diatomic gas, a very difficult molecule to administer, while hyaluronic acid and gelatin do not respond naturally to light. Using chemical modifications, we were able to bring together these three substances in a single formulation with the desired characteristics”, explains Laura Caetano Escobar da Silva, a researcher who participated in the development of the formulation.

Both hyaluronic acid and gelatin, used in the polymer solution, have been chemically modified to respond to light. The result is that the viscous liquid injected into the injury site turns into a hydrogel and begins to release nitric oxide in a continuous and prolonged manner. The formation of this hydrogel occurs when the solution is exposed to light guided by an optical fiber. The idea is that the solution can be applied using traditional infiltration techniques and gelled on site. With this, researchers guarantee greater adherence and better completion. “In this way, from the incidence of light, the molecules connect to form a three-dimensional network, which allows the release of the anti-inflammatory substance where and when we want”, explains Oliveira. After transformation, this resistant gel, with a high capacity to absorb water and biological fluids, works as a temporary replacement for cartilage.

Fewer side effects

The articular cartilage it covers the ends of the bones and acts as a kind of cushion between them, reducing friction and the impact caused by movement, explains IQ researcher Daniele Mayara Catori, who is working on developing the new formulation in her doctorate. “Due to the low irrigation of the cartilaginous tissue, there is little renewal of cells and nutrients in the intra-articular region, which impairs the recovery of the injured tissue, something completely different from what happens with bone tissue, for example. It was with this in mind that we selected the components of this formulation, aiming to provide a temporary matrix for cell growth and the necessary stimuli to assist local repair”, she comments.

When cartilage is damaged by trauma, disease, or simply reduces in size with age, the bones can rub against each other, causing pain and inflammation. While pain treatments with anti-inflammatory drugs only offer short-term symptom relief and can be harmful to the patient in the long term – and even restrictive for people with hypertension or diabetes – bioabsorbable hydrogel has a prolonged therapeutic effect on pain relief. and improving mobility, being slowly eliminated by the body while helping in the recovery process. “The bioabsorbable material, in contact with body fluids, will slowly release nitric oxide, from donor molecules that have anti-inflammatory action and without toxic effects on the body”, he explains. Catori.

Prolonged therapeutic effect

In initial bench tests, which simulate the conditions that the hydrogel would encounter in the human body, there was prolonged release of the anti-inflammatory molecule for at least fourteen days. The new polymeric material, according to Catori, has the potential to treat pain and stimulate cartilage tissue repair in early joint injuries caused by natural wear and tear, associated with aging, or by impact, such as what happens in injuries caused by accidents or physical activities with overload.

To reach the market, however, the technology still needs to pass several tests. The next stage of research is to conduct preclinical experiments, before beginning human clinical trials. As universities do not produce and sell products, the most appropriate procedure, provided for by Innovation Law, is technology transfer. Therefore, for the product to reach the market, technology licensing is essential, allowing advancement in technology development, testing and production on a commercial scale.

Licensing the technology to interested companies speeds up the process, ensures product quality, and, in return, the company has access to cutting-edge technology, contact with Unicamp inventors and reduced costs and risks in the development of products and processes innovative.

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This text was originally published on the Innovates Unicamp.