Osteoarthritis affects millions of people worldwide, and occurs when the cartilage that protects the ends of bones starts to degrade and wear down. With the aim of ultimately developing treatments for osteoarthritis, researchers from the Washington University School of Medicine in St. Louis have genetically engineered cartilage cells to release an anti-inflammatory drug when they undergo mechanical stress, such as that caused during bending of knees or lifting of heavy loads. Their research is part of a rapidly growing field called mechano-genetics, that studies the effect of physical and mechanical forces on genetic expression at a cellular level.
The cartilage cells that form the new cartilage tissue were engineered to release interleukin-1 receptor antagonist (commercially sold as Anakinra)—a factor known to reduce inflammation in arthritic joints. Although the drug has been shown to be safe in humans, its effectiveness is low in clinical trials because it is only injected once into a joint. The authors believe that continuous release of the drug in the joint over several years, especially when the joints are undergoing mechanical stress, will lead to significantly improved outcomes.
As a proof of concept, the authors tested their genetically engineered cells in mechano-responsive tissue constructs. In an inflammatory environment, the constructs with engineered cells were able to maintain the integrity of the tissues and the matrix in it, while constructs with regular cartilage cells had significant degradation of the tissues.
The paper, published in Science Advances, describes the framework for developing mechanically responsive engineered tissues as a novel approach for establishing new drug delivery systems using mechano-genetics.