Osteosarcoma is a relatively rare bone tumour that has a major impact on patients’ wellbeing. It is usually found in the bigger bones of the body. Often, substantial parts of the affected bone have to be surgically removed while remaining tumour cells are destroyed using radiation or chemotherapy. It is difficult, often impossible, to repair the bone after these interventions and the chance of recurrence is high.

Trying to tackle all of these issues, Sabine van Rijt will develop a nanocomposite biomaterial consisting of a hydrogel and nanoparticles. “Hydrogels are organic polymers that have similar properties to human tissues; they contain a lot of water and are also quite soft.” Hydrogels can be used for soft tissue applications such as skin, but are usually not suitable for stiffer tissue like bones.

Growing back together

Hydrogels can be engineered to be self-healing. After the bonds between the polymers are broken, either because they do so naturally or due to particular stimuli, the gel completely reforms without visible ruptures; it grows back together. “In tissue engineering and regenerative medicine, this is useful because it emulates human tissues’ ability to heal. The tissue can remodel its environment.” Another advantage of self-healing hydrogels is that they can be injected into the damaged site and reformed into any shape to replace the missing tissue. Over time, the material should degrade and be replaced by human tissue.  

Van Rijt’s project is innovative in its use of inorganic nanoparticles to form composite materials. “Even though they’re tiny, they have a high surface area and we use this property to form multiple bonds with the polymers of the hydrogel. That makes the gel much stiffer. At the same time these bonds are reversible.” Preliminary data shows that the nanoparticles heavily fortify the hydrogel without diminishing its self-healing properties. “We want to optimise the self-healing materials by tuning bond kinetics, so manipulating the rate at which these bonds form and break.”

The nanoparticles can also give the composite material additional properties. “They are highly bioactive; that means they signal to the surrounding tissue to promote bone formation.” As the material degrades, the nanoparticles are released, taken up by cells and there stimulate tissue formation. The material is thus gradually replaced by actual bone.

Growing back the bone

Van Rijt also managed to modify nanoparticles to have anti-osteosarcoma properties. “We can create particles that are very selective towards bone cancer cells without being overly toxic to other cells, so it has a selective chemotherapeutic effect. We hope to have one kind of nanoparticle that kills the remaining osteosarcoma cells and then a second type promoting the growth of bone. Ideally, they would be released one after the other. In these patients, delivery would not be an issue; surgeons could apply the material right after removing the diseased bone.”

While the nanocomposite biomaterials are developed for application in bone cancer, the research also fundamentally investigates the mechanisms of these novel materials for a much wider range of applications in biomedical science. Nano4Bone, which would also be an excellent name for an R&B quartet, sees many of Van Rijt’s research lines coming together.