-The road to a bio-artificial joint-
Osteoarthritis (OA) is a form of joint degeneration that causes continuous pain and restriction of movement in 40 million Europeans. In the Netherlands, 1.26 million people have osteoarthritis in one or more joints and the expenditure in 2017 on care for osteoarthritis amounted to EUR 1.2 billion. (1.4% of the total healthcare costs in the Netherlands). It is the fastest-growing cause of disability worldwide. Once damaged, the degradation of the joint surface, especially the cartilage and underlying bone, continues to deteriorate. This is also accompanied by damage to other tissues, such as the meniscus and the mucous membranes in the joints. In the majority of cases, this is a non-reversible process.
Unfortunately, clinical intervention is not always successful and usually only has a temporary effect. As a result, a large number of patients will receive a total joint replacement prosthesis. Implantation of, for example, a total knee or hip prosthesis is usually successful, with pain being adequately controlled. Unfortunately, such a prosthesis needs to be replaced after an average of 15-20 years. In addition to the onset of osteoarthritis of the knee at a young age and the increase in life expectancy and activity of the elderly, the number of prostheses that need to be replaced is increasing explosively. This is a complex and expensive procedure, which is much less successful than the first procedure. For this reason, it is desirable to postpone as long as possible the moment when the first prosthesis is placed and to strive for "biological" solutions.
What does it mean for patients?
There are several ways to treat damage to the joint surface. The most advanced technique tries to fully repair a cartilage defect by reimplanting cartilage cells from the patient's own cartilage at the damaged site, whether or not supported by a firming gel of biomaterials. This technique is called autologous chondrocyte implantation (ACI). It is mainly used as a treatment for defects caused by acute injury. Disadvantages are that it works especially in young patients, it requires two operations, it is expensive and the rehabilitation time is long with limited load capacity. Even when the treatment has been successfully completed, newly formed tissue usually cannot completely fill in the structural organization and properties of healthy cartilage. This is essential for bearing the load during movement. As a result, it may ultimately fail and the patient may suffer again.
What do we do in the RegMed XB Moonshot?
The aim of the Osteoarthritis Moonshot is to develop an affordable treatment that is suitable for more people. We want to develop a biomechanically smart functional implant that immediately restores pain-free function. Additionally, this implant should promote the restoration of natural joint cartilage. It can be used for more patients because it can be used for a wider range of damage, both in terms of location in the joint, in terms of the size of the damage, and also because it can be used for a wider age group.
The primary goal of the first years in RegMed XB is to create a biotechnologically regenerative bone cartilage implant for focal defects (e.g. in the knee) or for replacement of small joints (e.g. thumb joint). For the entire Moonshot, we want to use the knowledge we now gain in the manufacture of new biotechnological living joints for whole or partial joint replacements.
A first design for the 3D printed implant turned out not to have the same properties as we would expect for cartilage. That's why we designed a second generation at the beginning of 2020 with a layered structure that functions much better, testing is now taking place. In addition, the interaction with and encapsulation of cells is also investigated. An important part of this project is the testing of the implants in bioreactors. To this end, a standardized protocol has been developed to perform step-by-step mechanical tests. Preliminary results show promising results. To test the implants in a more physiological way, a more rigid testing system is now being developed.
For small implants, it is foreseen that these will be filled with cartilage cells from the patient himself. However, when we go for larger implants or joints there will have to be an alternatives for these cells, most likely from stem cells grown in the lab. These lab-grown cells will also be used during the tests outside the body and for animal testing. Good steps have been taken with the growth of cartilage cells in the lab. It turned out that the growth of human cartilage could be accelerated by certain biological factors. Also, cartilage-derived stem cells were successfully isolated from human cartilage, confirmed by successful growth in three different cell lines. Their potential to be used for cartilage regeneration is currently being investigated. Work is currently underway to assemble all the components and to design a preclinical pathway.