Mimicking articular cartilage, which enables seamless movement in the knee and hip joints, is a complex task. Damage to this cartilage often results in pain, compromised function, and arthritis. A potential solution lies in implanting artificial protein-based scaffolds that aid cartilage self-regeneration as the scaffold gradually degrades. The success of the regeneration largely depends on the scaffold's ability to mimic the biological properties of cartilage. However, marrying the seemingly incompatible properties of stiffness and toughness has remained a challenge for researchers. Now, a new method can be used to create a biodegradable gel that combines stiffness and toughness, advancing the quest to develop biodegradable implants for joint injuries.

Creating a biodegradable cartilage implant calls for a delicate blend of stiffness and toughness, similar to natural cartilage. Mechanically, a stiff object resists bending or deformation but is typically brittle, breaking when bent, much like glass. A tough object, on the other hand, resists breaking when bent but might be too soft for use in a joint, like jelly, or even softer than natural cartilage. Current protein-based implants reflect this mismatch between cellular requirements and what's being provided, hampering optimal cartilage repair. Researchers at University of British Columbia (UBC, Vancouver, Canada) and Nanjing University (Nanjing, China) have jointly pioneered a novel approach to stiffening a protein gel without compromising toughness, by physically intertwining the chains of a specific protein that forms the gel's network.

These interlocked chains can move, enabling the dissipation of energy, similar to shock absorbers in bikes, created by activities such as jumping. The researchers also merged this with a known method of folding and unfolding proteins for additional energy dissipation. The resulting gel was extremely tough, resisting incisions with a scalpel, and stiffer than other protein hydrogels. Its compression resistance was among the highest for such gels and compared favorably with actual articular cartilage. Additionally, the gel rapidly regained its initial shape post-compression, mimicking real cartilage after jumping. Rabbits implanted with this gel exhibited significant signs of articular cartilage repair 12 weeks post-implantation, with no remaining hydrogel and no rejection by the immune system. The researchers observed bone tissue growth similar to existing tissue, and regenerated tissue adjacent to existing cartilage in the gel implant group—significantly better outcomes than those observed in a control group.

Surprisingly, a stiffer variant of the gel yielded better results than a softer one, likely due to higher stiffness being more compatible with bone and cartilage tissues, thereby providing a physical cue to the body for effective regeneration. However, extreme stiffness did not yield optimal results, possibly due to slower body degradation, according to the researchers. The research, while promising, is still in its early stages for human trials and requires further animal testing. The researchers' future steps include testing and refining the current gel composition and introducing additional biochemical signals to further enhance cell regeneration.

“Cartilage is tricky,” said senior author Dr. Hongbin Li, a professor in the UBC department of chemistry. “Articular cartilage repair represents an important medical challenge because naturally speaking, it doesn’t repair itself."

“By optimizing both biochemical and biomechanical cues together, we will see in the future whether these new scaffolds can lead to even better outcomes,” added Dr. Li. 

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