CARTHAGO ITN

Cartilage and disc repair in tissue and organ culture

Degeneration of cartilage has different phases. Depending on the degree of degeneration, we can apply different treatment methods. In the early stage of osteoarthritis (OA) and intervertebral disc degeneration leading to chronic low back pain, inflammation happens before structural change to the tissue. Inflammation is the body’s natural response to fight off injuries. However, in OA and disc degeneration there is more inflammation than needed, causing unnecessary damage to the tissue and consequently, pain. Therefore, reducing inflammation can stop degeneration of cartilage and disc tissue. In this project, we have multiple strategies to inhibit inflammation. We found a very promising compound derived from the plant Ginseng, which is used as traditional chinese medicine. The medicinal benefits of Ginseng have been proven in numerous different fields of medicine, from stopping cancer, to improving heart function. For OA treatment, the anti-inflammatory properties of ginseng may especially interesting. However, it is not fully known at the moment which component of ginseng is exactly responsible for its benefits, which is what we aim to find out in our research. Once we know the active component of ginseng, we aim to deliver it to the damaged cartilage using a special material known as bio-synthetic cellulose. This bio-synthetic cellulose can be used as a skin patch, and by including the drug into the skin patch, we can improve delivery of the drug to the cartilage. The use of this skin patch reduces the need for painful injections, and would improve comfort for OA patients.

In later stages of disease, the breakdown of cartilage and disc tissue is more severe. At this point, the body is not able to regenerate the tissue anymore. In this case, a more drastic approach is necessary to improve joint function. One of our strategies is to replace the lost cushion with a hydrogel very similar to the natural cartilage. This material is composed of 98% water and hyaluronic acid, which is one of the main components of cartilage and the disc. This allows us to inject it directly into the affected joints without need for surgery. This hydrogel acts as a base in which new, healthy cartilage and disc cells can be delivered and multiply. Furthermore, these healthy cells can regrow the damaged tissue. Besides cells, the hydrogel can also contain anti-inflammatory drugs. This way, all aspects of OA, being damaged tissue, inflammation, and pain, are tackled with one treatment.

In OA, there is often a misbalance in the kind of genes that are active or inactive in the cartilage, leading to inflammation and damaged cartilage. Another way to stop this inflammation is by rebalancing the activity of these genes. Using gene therapy, we can either activate or inactive the expression of certain genes. We found a kind of amino amine nanoparticle that very effectively and safely delivers this gene therapy to cartilage cells. Interestingly, the previously mentioned hydrogel can also be used to deliver this gene therapy into cartilage cells, thereby combining different strategies of treating OA.