A common definitive solution for stiff door hinges and degenerated knee joints is to have them replaced. In the latter case, however, knee joint replacement entails a great deal of pain and a long road to recovery.
When the cartilage that serves as a shock absorber in our joints gets degraded by oxidative stress caused by inflammation, friction between the adjacent bones causes persistent pain. This is often diagnosed as osteoarthritis.
“Currently, effective treatments for osteoarthritis are lacking as cartilage does not self-regenerate,” said Dan Kai, a Scientist at A*STAR’s Institute of Materials Research and Engineering (IMRE). In a collaborative effort, the team led by Li Zheng from Guangxi Medical University in China developed a novel nanofibrous biomaterial made of lignin, commonly found in wood, that promotes cartilage regeneration.
Capitalizing on the strong intrinsic antioxidant activity of lignin, the team modified the surface of lignin by polymerizing it with an FDA-approved polymer, poly (ɛ-caprolactone) (PCL), creating a soft and flexible biomaterial with mechanical properties like cartilage tissue.
To determine the effectiveness of the antioxidant properties of PCL-lignin nanofibers, the team treated human chondrocytes, which are cells that make up joint cartilage, with hydrogen peroxide and measured the amount of cell death with or without PCL-lignin. They found the survival rate of cells grown on PCL-lignin to be twice of those grown without the nanofiber.
At the molecular level, the better survival rate was attributed to PCL-lignin activating antioxidant enzymes through an intracellular process called autophagy. Simultaneously, autophagy facilitates the removal of biomolecules damaged by oxidative stress, thereby suppressing the accumulation of potentially toxic substances inside the cells.
“Compared to commonly used antioxidants such as vitamin C or E, our lignin-based biomaterials have more stability and their antioxidant effects last longer,” said Kai.
When tested in a rabbit model of osteoarthritis, the nanofiber gradually released lignin into the joint space, exhibited anti-inflammatory effects and repaired the damaged cartilage tissue over a period of four weeks.
“Osteoarthritis management mainly focuses on pain relief and reducing inflammation through non-steroidal anti-inflammatory drugs and steroids. Our nanofiber now provides a new approach for treatment as it can reduce inflammation and promote cartilage regeneration,” added Kai.
Meanwhile, the team is planning to develop new lignin-based biomaterials such as gels that can be used during minimally invasive surgeries.
“To further demonstrate the function and safety of these biomaterials, we will be carrying out more animal studies and pre-clinical trials before transiting into human clinical trials,” he said.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Materials Research and Engineering (IMRE).