New gel could produce biodegradable implants for joint injuries

 "Cartilage is tricky," says senior author Dr. Hongbin Li, a professor in the UBC department of chemistry. "

Biodegradable cartilage implants must be tough enough to resist being bent or deformed but soft enough to be useful in a joint. This is a combination that is hard to achieve.

Dr. Li and his team engineered a new method for stiffening a soft protein gel without sacrificing its toughness, by physically tangling together the chains of a particular protein that make up the gel's network. 

"These entangled chains can move, which allows energy, for instance, the impact from jumping, to be dissipated, just like shock absorbers in bikes. In addition, we combined this with an existing method of folding and unfolding proteins, which also allows for energy dissipation," explained first author Dr. Linglan Fu, who conducted the research as a doctoral student at UBC's department of chemistry.

The outcome was a gel with some pretty neat properties. It could resist compression at the same level as actual articular cartilage and could rapidly recover its original shape after compression.

The researchers then implanted rabbits with the gel. The animals showed notable signs of repair of articular cartilage 12 weeks after implantation.

The scientists however noted that they needed to balance stiffness and softness as the stiffest gel did not work as well. 

"This just shows how complex this area of research is, and the need to take into account the many different physical and biochemical cues and factors when designing these scaffolds," said co-author Dr. Qing Jiang, a professor and surgeon at Nanjing University.

The research is still too premature for human trials but next steps will consist of fine-tuning the current gel composition and adding additional biochemical cues to further promote cell regeneration. 

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

The study is published in Nature.

Study abstract:

Load-bearing tissues, such as muscle and cartilage, exhibit high elasticity, high toughness and fast recovery, but have different stiffness (with cartilage being significantly stiffer than muscle). Muscle achieves its toughness through finely controlled forced domain unfolding–refolding in the muscle protein titin, whereas articular cartilage achieves its high stiffness and toughness through an entangled network comprising collagen and proteoglycans. Advancements in protein mechanics and engineering have made it possible to engineer titin-mimetic elastomeric proteins and soft protein biomaterials thereof to mimic the passive elasticity of muscle However, it is more challenging to engineer highly stiff and tough protein biomaterials to mimic stiff tissues such as cartilage, or develop stiff synthetic matrices for cartilage stem and progenitor cell differentiation1. Here we report the use of chain entanglements to significantly stiffen protein-based hydrogels without compromising their toughness. By introducing chain entanglements into the hydrogel network made of folded elastomeric proteins, we are able to engineer highly stiff and tough protein hydrogels, which seamlessly combine mutually incompatible mechanical properties, including high stiffness, high toughness, fast recovery and ultrahigh compressive strength, effectively converting soft protein biomaterials into stiff and tough materials exhibiting mechanical properties close to those of cartilage. Our study provides a general route towards engineering protein-based, stiff and tough biomaterials, which will find applications in biomedical engineering, such as osteochondral defect repair, and material sciences and engineering.