Bioprocess engineer Jos Malda is on the verge of moving with the Utrecht Biofabrication Facility to the new Regenerative Medicine Center Utrecht. Utrecht University and the University Medical Center Utrecht are jointly investing in the development of new regenerative techniques. Since early 2015 Malda has led the research group at the Department of Orthopaedics, which is moving to the new centre. There, he will find fertile ground for his recently announced ERC Consolidator Grant. Malda develops three-dimensional prints made of gel, fibres and living stem cells, which serve as implants for damaged joints. The ultimate objective is to get the chondrocytes to regenerate the tissue: a technique that might allow today’s knee and hip operations to be replaced in future. In the coming years, the researchers will test various materials in the bioreactors developed by Malda, and investigate how the cells react.
Sitting amongst the removal boxes, Malda shows a model of a knee bone and an accompanying piece of plastic that fits seamlessly into the place where the bone has been damaged. “Using MRI scans, we can make 3D prints of an eroded joint, so that doctors can repair the damage in a completely customised way.” The implants have to satisfy many demands. “There is a lot of pressure on joints, the implant has to be strong enough to cope with that.” In the coming years, with his multidisciplinary research team Malda will develop implants that partly consist of living stem cells. These cells stimulate the embedded cells to make new cartilage tissue; in other words, a regenerative, rather than a reparative process occurs. The technique however still faces challenges. “We will test various materials and use bioreactors to investigate the optimal internal architecture of the constructs that we want to implant. The plugs consist of layers of hydrogel, living cells and biodegradable plastic fibres.”
Malda developed bioreactors that enable the researchers to test this technique in a more natural environment. “At present, the plugs and the bioreactors are still small, but I am trying to make them larger. Ultimately, we want to evaluate larger impants that can regenerate a large part of the articulating surface.”
Human and veterinary medicin
In order to achieve succesful regeneration of tissues, the implants have to meet a number of specific requirements. “It is difficult to construct the implant in such a way that it breaks down slowly to make space for the growth of new chondrocytes. The degeneration must take place at the same pace as the growth. As part of this process, the hydrogel breaks down first and the fibres later. This allows the implant to retain its stiffness.”
Malda’s work is connected with both human and veterinary medicine. “The two disciplines can learn from each other. For example, there is a great deal being invested in aiding the recovery of the knee joints of horses [JM1] and that is teaching us more about the regenerative behaviour of cells in general. This expertise is also of interest to human medicine."
Hip and knee operations
The impact of this 3D regenerative technology will be enormous. For instance, today’s artificial hips and knees have to be replaced after ten to fifteen years. Therefore, many elderly people who need a hip or knee operation postpone the operation for as long as possible, even when they are in pain. “In the future, we can intervene in the cartilage as soon as damage appears", explains Malda, enthusiastically. "Our implants disappear over time and are replaced by regenerated tissue.”
The technique is not limited to knees and hips; it may also be possible to use it for other parts of the body. “If we are able to stimulate cells to repair themselves in situ, then we may also be able to use this in other parts of the body: for oral and maxillofacial surgery, for example.”
Text: Youetta Visser