Our bones have amazing self-healing powers and are capable of completely repairing most fractures and injuries. However, they reach their limits in the event of major damage. If the injury to the bone – for example as a result of serious accidents or tumours – is so extensive that it cannot heal on its own, it is called critical-size bone defects. To date, doctors have been using various options for their treatment: they use bone material from other parts of the body, insert titanium implants or use bone material from human and animal donors.

However, all these methods have disadvantages: donor tissue from humans or animals provokes rejection reactions; with titanium implants in the head area, patients complain about the high weight of the implant. And taking bone tissue from one place and implanting it elsewhere only shifts the problem for the time being: “When there is damage in the dental area, for example, bone material is often taken from the hip,” explains Professor Edda Tobiasch, head of the PersoImplant project. “But this can result in patients having to sit in a wheelchair for months until their hips are stable again.”

Stem cells can reproduce almost any tissue

That is why the scientist and her team want to find another way to repair bone damage – and they are betting on stem cells: these are cells that have not yet developed into a specific cell type, but can in principle transform into any tissue. In addition to the ethically controversial embryonic stem cells, there is another type, so-called adult stem cells, which many body tissues keep in reserve in order to grow and regenerate. Although these cells are already somewhat more firmly established than those of an embryo, with the right means they can be “nudged” in the right direction of development. But they have one decisive advantage above all: since they can be taken directly from the patient’s body, they are recognised as endogenous cells and do not provoke a rejection reaction.

So, in theory, the idea of PersoImplant sounds quite simple: you take some stem cells from a patient with a severe bone defect, place them on a carrier material, let them grow on it and make them develop into bone tissue. This results in a kind of living, endogenous implant which is inserted into the patient and then adheres to the damaged bone. That is the long-term goal of this work – although the head of the project points out that, at the university, she can only achieve this goal to a limited extent: “The subsequent clinical phases, as the name suggests, can only be carried out in clinics.”

The devil is often in the details – especially in research

In practice, developing the basis for the “personal implant” has presented the project team with several challenges. For example, nobody knew which stem cells were best suited for the project. “We wanted to minimise the risk of the cells developing into the wrong cell type,” explains Tobiasch. An important part of the project was therefore the search for the best donor tissue – a comparison that no one has ever made before. For the time being, the scientist will only reveal so much about the result: “The differences between the tissues are impressive.”

In addition, the team developed a technique to steer the cells in the right direction of development – by blocking or activating certain receptors on the cell surface. In this regard, however, the researchers are struggling with the so-called burst release: the active substances are encapsulated and are intended to be released gradually, because the transformation of stem cells into specialised tissue cells can take several weeks. So far, however, the active substances do not meet this requirement. As they are mostly water-soluble substances in an aqueous environment, the entire dosage is released at once, or at least in far too short a time. The search for the right capsule technology will therefore continue for some time.

At least as important for the project is the suitable carrier material: it should be as similar as possible to natural bone tissue and be biocompatible, that is, it must not provoke a rejection reaction or secrete toxins. And as if these requirements were not high enough, the carrier material would actually have to change with each healing step: First of all, it needs to promote the transformation of stem cells into bone tissue. It would then have to get the cells to grow in three dimensions instead of just on one surface. And, last but not least, it needs to be degraded in a controlled manner – but of course not until its work is done.

“The materials developed so far cannot meet all these requirements equally well,” says cooperation partner Professor Margit Schulze, who is also a researcher at the Bonn-Rhein-Sieg University of Applied Sciences and is responsible for the carrier materials in the project. The PersoImplant team has thus concentrated on carriers that support stem cell differentiation and are also easily degradable. According to Schulze, hybrid materials consisting of a cement-like component for strength and a component similar to the natural collagen in bone have proven to be the most suitable for this purpose.

Positive summary at the end of the project

As the PersoImplant project officially ends in January 2020, project head Edda Tobiasch summarises the work. It was, she reports, an exciting project with many setbacks, but which also brought new insights. “In general, we know much less about bones than is generally believed,” explains the researcher – but that is what makes her work so fascinating. Two other teams have just published studies that add new theories to existing assumptions about bone healing and stem cell differentiation. A stroke of luck for Edda Tobiasch: the new findings will also help her to continue her work. In the meantime, a follow-up project (Hybrid KEM) for PersoImplant is already under way which is dedicated to open questions and is also funded under the IngenieurNachwuchs funding line.

Edda Tobiasch is satisfied with what her team has achieved so far despite all the difficulties. “Research doesn’t always go the way you want it to,” she says. “Not every day brings a new little piece of the puzzle. Sometimes the whole picture suddenly becomes bigger, more complex, and you are suddenly further away from the goal than you thought. But sometimes you can also put a larger piece into the overall picture. In any case, it stays exciting, and every piece is a step forward and therefore an advantage for the future patients.”