Researchers from KU Leuven and University Hospitals Leuven have managed to engineer living implants in the lab by mimicking how bone tissue is created in an embryo. The technology paves the way for bone-regenerating tissue implants created on an industrial scale using 3D bioprinting. The researchers expect the first living implants to be available to patients in four years.

Scientists have long been searching for a way to create living implants to replace missing bone tissue. Patients with large bone defects, for instance after an accident or infection, are currently treated with healthy bone tissue taken from that same patient, or from someone else. Both approaches have serious limitations and side effects. Therefore, alternative treatments with predictable clinical outcomes that allow healing of large bone defects are urgently needed. 

In a study recently published in Advanced Science, researchers from KU Leuven and University Hospitals Leuven developed a novel method to address this challenge. “We looked at how long bones are developed in the embryo, as this process is similar to what happens when a fracture successfully heals. By copying this natural process, our technology resulted in successful bone formation and healing in live models,” said Professor Ioannis Papantoniou from the Prometheus division at KU Leuven. Together with Professor Frank Luyten, he led the team that successfully translated this strategy into reality.

Regeneration

The callus organoids were engineered in such a way that they can grow bone micro-organs with bone marrow compartments. Using these organoids as building blocks, larger implants were assembled and successfully healed long bone defects in mice in six to eight weeks, regenerating the whole bone. The organoids were grouped to fit the shape and size of the defect. 

This strategy paves the way for affordable, transplantable organs and tissues.

Professor Luyten explains: “This technique will allow us to produce tissue on an industrial scale in the near future. The construction of organoids is still done manually, but will soon be replaced by robotics.” Prometheus is coordinating a European Horizon 2020 research project, JointPromise, to further develop the scale-up and automation of the technique as well as the tissue assembly by using high precision bioprinting. 

Personalised implants

“In preparation for the use of the new, engineered living implants in patients, we have been conducting experimental research with laboratory animals for many years, imitating the application in human beings down to the smallest detail,” says orthopaedic surgeon Johan Lammens of KU Leuven and University Hospitals Leuven. “We want to be ready to use the new bone implants in patients.”

The research team believes that their findings will result in precisely engineered personalised implants. “This strategy can revolutionize future healthcare, paving the way to supplement the large need for affordable, transplantable organs and tissues,” Professor Luyten says. Bone tissue will likely be the first application, but the method can also be used to grow other tissues such as heart, liver, or kidney.

The study ”Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing” by Gabriella Nilsson Hall, Luís Freitas Mendes, Charikleia Gklava, Liesbet Geris, Frank P. Luyten, and Ioannis Papantoniou was published in the journal Advanced Science.