2023-06-21 17:31:35
Mimicking articular cartilage, found in the knee and hip joints, is challenging. This cartilage is key to smooth joint movement, and if injured, can cause pain, reduce joint function, and cause arthritis. One possible solution is to implant artificial scaffolds made of proteins that help cartilage regenerate as the scaffold biodegrades. The regenerative capacity of cartilage depends on the scaffold’s ability to mimic the biological properties of cartilage, and to date, researchers have endeavored to combine the seemingly incompatible properties of stiffness and toughness.
Now, a new study by Canadian and Chinese scientists published in the journal «Nature» describes a method for combining these properties in a biodegradable gel. “Cartilage is complicated,” says Hongbin Li, lead author and professor in the Department of Chemistry at the Universidad British Columbia (Canada). “Articular cartilage repair represents a significant medical challenge because, naturally, it does not repair itself.”
Biodegradable cartilage implants must strike a delicate balance, as they must be both rigid and strong, just like real cartilage. Mechanically, when something is rigid, it resists being bent or deformed, but that usually means it’s brittle: when it bends, it breaks, just like glass. When something is hard, it resists breaking, even when bent, but may be too soft to be useful in a joint, like jelly, or even softer than real cartilage. That’s what happens with today’s implants, which are made of protein, creating a mismatch between what cells need and what’s being provided, Li explains. This causes the cartilage to not repair itself as well as it could.
In the study, Li and his team developed a new method to stiffen a protein gel without sacrificing its hardness, by physically entangling the chains of a particular protein that made up the gel’s network. “These tangled chains can move, allowing energy to be dissipated, for example from impact when jumping, just like shock absorbers on bicycles. Furthermore, we combined this with an existing method of folding and unfolding proteins, which also allows energy to be dissipated,” explains first author Linglan Fu.
The resulting gel is super-strong, capable of withstanding cutting with a scalpel, and stiffer than other protein hydrogels. Its ability to resist compression was one of the greatest achieved by this type of gel and compared favorably with real articular cartilage. In addition, the gel quickly returned to its original shape after compression, just like real cartilage after jumping.
Rabbits implanted with the gel showed remarkable signs of articular cartilage repair 12 weeks after implantation, with no traces of hydrogel remaining and no rejection of the implant by the animals’ immune systems.
The gel quickly returned to its original shape after compression, just like real cartilage after a jump
The researchers also observed bone tissue growth similar to existing tissue and regenerated tissue close to existing cartilage in the gel implant group, much better results than those obtained in the control group.
Interestingly, a stiffer version of the gel performed better than the softer version, probably because the higher stiffness is more compatible with bone and cartilage tissues and thus provides a physical signal to the body for effective regeneration.
However, according to the researchers, the stiffer gel did not work as well, probably due to its slower breakdown in the body. “This demonstrates the complexity of this field of research and the need to take many physical and biochemical factors into account when designing these scaffolds,” says co-author Qing Jiang, a professor and surgeon at the Nanjing University.
More animal trials are needed and the research is still premature for human trials. The researchers’ next steps include these tests, the refinement of the current composition of the gel and the addition of additional biochemical signals to further encourage cell regeneration. “By jointly optimizing the biochemical and biomechanical signals, we will see in the future whether these new scaffolds can produce even better results,” Li says.
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