Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the US alone is over $120 billion and is expected to grow significantly as the population increases and ages in the coming decades. Despite the broad impact of this disease, none of the available treatments can halt, reverse or change the course of progression. For severe joint disease, replacing the joint surfaces with artificial materials (total joint replacement) is the only available solution. However, the artificial joints seldom restore a full range of movement, and they have an increasing risk of failure over time. While the number of joint replacements approaches 1 million annually, approximately 160,000 joint replacement recipients must undergo a second "revision" surgery to correct complications. Revision surgery is technically demanding and is associated with substantially more surgical complications. Therefore, there is a major and rapidly growing clinical need for an alternative to the present-generation joint replacement devices. A biological replacement is universally regarded as the next major advance in joint replacement.
Our objective is to develop a biological construct for joint repair that combines naturally occurring biomaterials with functioning tissue derived from stem cells. We propose to create large osteochondral (bone and cartilage) constructs replicating an entire joint. This biological "device" will be used to replace and repair a large area of a damaged or degenerative knee joint and be functional immediately after it is implanted. The complexity of the problem and the challenges of the approach require a multidisciplinary approach. We therefore propose to assemble a team of leading experts in the fields of orthopaedic surgery, rheumatology, bioengineering, chondrocyte and stem cell biology, and biomaterials and scaffold assembly.
Our proposal's novel approach will combine technologies that are individually feasible. We will use recently developed biomaterials that are compatible with the human body and resemble native cartilage and bone. We possess the capability to assemble biomaterial scaffolds that mimic the shape of almost any articular joint. We can regulate the proliferation and differentiation of stem cells and can grow cartilage and bone tissue in bioreactors. We now have the opportunity to combine these independent technologies into one unified approach to repair or replace entire joints with a functional prosthesis.
Arthritis is the most common disabling disease. Over 10% of Californian residents suffer from some form of arthritis, the most common being osteoarthritis. This number will increase dramatically as the entire population in general and the “baby boomer” segment in particular, ages. The socioeconomic burden of medical treatment combined with lost productivity is close to $20 billion a year in California alone. Despite the vast amount of money spent in “treating” osteoarthritis, no treatment approach has been successful in preventing, reversing, or changing the course of osteoarthritis.
This grant proposal falls under the mission statement of the CIRM of funding innovative clinically relevant research. The proposal will result in the clinical application of tissue- engineered products from stem cells. Specifically, a biological replacement for arthritic joints will address the existing weaknesses and complications of traditional joint replacement with artificial biomaterials. A biologic replacement would also allow younger patients to benefit from this surgery and would dramatically reduce the number of complications from artificial replacement. A biologic replacement could also be expanded to replace joints and bones affected by traumatic injuries, cancer, or other diseases. If successful, this will further validate the significance of the CIRM program and will help maintain California's leading position at the cutting edge of biomedical research.
California has been at the forefront of biomedical research for more than 40 years and is internationally recognized as the biotechnology capital of the world. The recent debate over the moral and ethical issues of stem cell research has slowed the progress of scientific discoveries in this field especially in the US. The CIRM is a unique institute that fosters ethical stem cell research in California. The CIRM also serves as an exemplary model for similar programs in other states and countries.