The study in brief: Overall, the study shows that it is possible to create safe, cell-free tissue structures that effectively help the body build new bone tissue. The results meet key requirements for moving forward to the first clinical studies in humans.
Basic research, preclinical bone research /researcher-initiated study / in vitro (human tissue) and in vivo (mice and rats) / peer-reviewed study published in PNAS.
Bone and skeletal injuries cause extensive and long-term functional impairments worldwide. In a new study, researchers at Lund University in Sweden show how a cell-free cartilage structure can safely guide bone repair without triggering strong immune responses. The transplant has been successfully tested in animal models, and the next step is to evaluate the tissue engineering approach in humans.
When large portions of bone tissue are lost – for example due to cancer, painful joint diseases such as rheumatoid arthritis and osteoarthritis, or infections – the body's own capacity for repair is often insufficient. This can lead to significant functional impairment and require bone tissue transplantation.
It is estimated that over two million people worldwide are thought to need such transplants every year. Current techniques rely on using the patient's own cells or tissue for repair or regeneration. In addition to personal suffering, this entails high healthcare costs for society, according to the researchers behind the study.
Non-patient-specific technology
"Patient-specific grafts are both costly and time-consuming and do not always succeed. A universal approach in tissue engineering, with a reproducible manufacturing process, offers major advantages. In our study, we present just such a method and demonstrate important advances toward a non-patient-specific technology," says Alejandro Garcia Garcia, associate researcher in molecular skeletal biology at Lund University.
In the study, the researchers created cartilage in the laboratory, which was then rendered completely cell-free – a process known as decellularisation. During this process, the extracellular matrix is preserved – i.e., the natural support structure surrounding cells in tissue, which functions both as a scaffold and a signalling system. Growth factors are embedded within the remaining cartilage structure, providing the body's own cells with instructions on how damaged tissue should be repaired and rebuilt step by step.
"The cartilage structure we have developed is based on stable, well-controlled and reproducible cell lines, and can stimulate bone formation without triggering strong immune reactions. We show that it is possible to create a ready-made, so-called 'off-the-shelf' graft that interacts with the immune system and can repair large bone defects. Because the material can be produced in advance and stored, we see this as an important step toward future clinical use of human bone tissue transplants," says Paul Bourgine, who led the study. He is an associate professor and researcher in molecular skeletal biology at Lund University.
Next step – scaling up and standardising
This method means that the cartilage structure can be manufactured in advance and used for many different patients, without the need for customisation for each individual. The next step is to test the method in humans and to plan for scaling up and standardising the manufacturing process.
"The next step involves deciding which types of injuries to test this on first, such as severe defects in long bones of the arms and legs. At the same time, we need to develop the documentation required for ethical review and regulatory approval to conduct clinical trials. In parallel, we are establishing a manufacturing process that can be carried out on a larger scale while maintaining the same high level of quality and safety every time", says Alejandro Garcia Garcia.
