Researchers at the University of British Columbia have developed a protein-based hydrogel that is highly adapted for articular cartilage repair. A major challenge in creating biomaterial therapies to repair damaged articular cartilage is matching the mechanical properties of this highly specialized tissue. Cartilage is very tough, resisting breaking under force, but also very stiff, meaning that it resists being bent or deformed. To date, it has been difficult to create biomaterials that match these properties, and mismatched materials tend to produce poor quality cartilage healing. These researchers looked at the structure of native cartilage, which contains entangled collagen and proteoglycans, as inspiration for a new biomaterial. Their protein hydrogel contains entangled protein chains, which allows for a tough and stiff material, and has shown promise in healing damaged articular cartilage in animals.
Articular cartilage is easily damaged and less easily repaired. This specialized tissue lines our hip and knee joints, and provides a slippery and smooth surface where these bones interact. As it gets a lot of wear during daily activities, it is both tough and stiff, helping this dynamic tissue to fulfill its role over our lifetimes. However, when articular cartilage is damaged, it has very limited potential to heal itself, leading researchers to turn to biomaterials in an effort to create implantable scaffolds that can enable cartilage regeneration.
Creating a material that is both tough and stiff is not as easy as it sounds. Stiffness implies that a material can resist deformation, but many stiff materials are also brittle. Toughness implies that a material can resist being broken or torn, but such materials may be too soft and squishy for use as a cartilage alternative. Achieving the appropriate level of toughness and stiffness in such constructs, while also using biocompatible and biodegradable materials, is a tall order.
However, getting these mechanical factors right is important. In a tissue that is subject to frequent mechanical stress, achieving the correct mechanical properties in regenerative implants will yield dividends in improved tissue healing. A failure to create appropriate materials is a big factor in the lack of effective cartilage implants to date. These researchers studied the components of native cartilage as inspiration for their new material, noting that cartilage contains a network of entangled proteins.
The hydrogel they created contains an intentionally entangled protein network, whereby the protein chains have been physically entangled, leading to the magic combination of toughness and stiffness. “These entangled chains can move, which allows energy, for instance, the impact from jumping, to be dissipated, just like shock absorbers in bikes,” said Linglan Fu, a researcher involved in the study. “In addition, we combined this with an existing method of folding and unfolding proteins, which also allows for energy dissipation.”
So far, the researchers have tested the implants in damaged cartilage in rabbits, and observed significant healing with no immune rejection of the implants.
Here’s a video about the new hydrogels from University of British Columbia:
Study in journal Nature: Cartilage-like protein hydrogels engineered via entanglement