Leuven researchers have succeeded in cultivating organic bone tissue in the way bone tissue is created in an embryo. The technique used, which starts from small cartilage spheres, makes it possible to grow organic bone tissue on an industrial scale in a few years time and to build tissues with 3D bioprinting. "We expect the first live implants using this method in patients in four years' time".
Scientists have long been looking for a way to replace tissue such as bone with living biological implants. Previous studies suggested that developmental engineering, tissue engineering based on the knowledge from developmental biology, can be a good way to manufacture new growing tissues. Researchers first need to understand how bone tissue is formed in an embryo before they can mimic it in the lab. The process of fracture healing in a human being largely corresponds to the production of bone in a fetus during embryonic development.
A study recently published in the online science magazine Advanced Science shows that this method does indeed work. The researchers succeeded in removing human precursor cells from the bone and multiplying them into millions of cells. These cells were spontaneously allowed to stick together into small packages and eventually became cartilage-like pieces of tissue, which are the precursors of bone. The micro tissues or organoids then went into a mould in the form of the missing piece of bone. After implanting that piece of tissue into a mouse model with a bone defect, the cartilage behaved as in nature: it grew into a perfectly integrated piece of bone in the right shape in six to eight weeks.
Prof. Dr. Frank Luyten, rheumatologist at UZ Leuven and senior co-author of the study: "What is interesting about the technique is that it can be used to produce tissue on an industrial scale in the future. The construction of microfibres is still done manually, but will then be replaced by robotics". The research project JointPromise of the Prometheus platform has just received a European grant (Horizon 2020) to further develop this scale-up and automation.
Offering regenerative solutions for bone defects is known as a major unmet medical need. A patient who comes to the hospital today with a large bone defect, such as after an accident or infection, can be treated with techniques in which the still existing bone creates new bone by lengthening the leg. Such techniques produce considerable results, but are very time-consuming, not always efficient and often cause suffering to patients.
Prof. Dr. Johan Lammens, orthopedist at UZ Leuven and chief surgeon at Prometheus for bone repair: "In order to prepare for the new strategy with tissue engineering, we have been conducting experimental research with laboratory animals for many years, imitating the application in humans down to the smallest detail. In this way, we want to be ready to apply the new bone implants in patients".
Prof. Dr. Frank Luyten: "This new study lays the foundation for a technological development to make tissue pieces in the size and shape we want. Tissue engineering is 'in': everyone understands that we will be making biological tissues in ten to twenty years' time. This study also makes it clear in what way this will happen. Bone will probably be the first application for this method, but the technology can also be used to grow other tissues such as heart, liver or kidney".
Prometheus is a research department for tissue engineering at KU Leuven and a division of KU Leuven Research & Development. Prof. Dr. Frank Luyten is a rheumatologist at UZ Leuven and director of Prometheus. He has been doing research in regenerative medicine for more than twenty years. Prof. Dr. Johan Lammens is an orthopaedic surgeon who is an expert in distraction osteogenesis.
Translation based on press release by UZ Leuven
Pictures: UZ Leuven, Shutterstock