If we lose a limb or a finger wouldn’t the easiest approach to therapy be to grow a new one? This is a question that Dr. Freeman has been addressing, namely the process of tissue regeneration following injury or disease. Dr. Freeman is developing the new discipline, Plasma Medicine, that explores the use of a novel dielectric barrier discharge plasma system to enhance processes like cell differentiation, limb development, and regeneration of cartilage and bone. Aside from the obvious uses of such a system, she is assessing whether this type of bioelectric phenomena can also be used to reduce cartilage damage immediately after an injury, thereby slowing or preventing the development of osteoarthritis.
Infection is a serious complication of orthopaedic surgery; it can slow down healing, cause pain, loss of a limb, and even death. Moreover, the costs associated with infection can be extraordinarily high. Added to these problems, infections linked to knee and hip surgery are difficult to diagnose and hard to treat; thus, it is critical to find effective prevention strategies. One goal of the Hickok laboratory is to engineer materials used in joint or back surgery to be antibacterial, so as to prevent or eradicate infection. Dr. Hickok has developed a new type of chemistry that bonds antibiotics and antibacterial substances onto implants and even bone filling materials. These agents can be activated or released by ultrasound or, in some cases, a light beam. This revolutionary approach to infection control shows great potential in combating these devastating infections.
With the increase in sport injuries, few individuals can escape problems linked to tendon malfunction. If uncorrected, there is loss of function of the tendon, and painful and limited movement of joints. Dr. McBeath, a hand surgeon and clinician scientist, is engaged on an ambitious and exciting project to develop replacement tendons lost through aging, trauma, and degenerative disease. This is being achieved using devitalized human graft tendon, which is being repopulated with human tendon cells that progress to become the cells that anchor the soft tissue to the bone. These studies aimed at reengineering human tissues are carried out in a bioreactor. Once these studies are completed, the reengineered tendon will be used in a rabbit model of tendon regeneration, prior to being assessed for a clinical study in humans.
Fibrosis is a condition that results in the deposition of an excess of a disorganized protein called collagen in almost any tissue of the body. Following knee injury or knee replacement surgery, (arthro)fibrosis can cause a painful and debilitating condition known as “stiff knee.” Dr. Fertala, together with a group of orthopaedic surgeons that includes Dr. Beredjiklian, Dr. Abboud, and others, are examining novel ways to block excessive collagen production, with the goal of preventing abnormal scarring and improving recovery. Dr. Fertala has developed an antibody that reduces the amount of newly formed collagen fibrils in an injured joint, thereby improving the range of motion of an antibody-treated knee. Ongoing studies will define the benefits and limitations of the proposed approach to limit post-traumatic stiffness of joints and test its clinical potential.
The intervertebral disc is a complex structure that separates opposing vertebrae, permitting a range of motions and accommodating high biomechanical forces. The interaction between the semifluid interior of the disc and the tight molecular lattice of the surrounding ligament-like tissues provides spinal stability. Disturbing this relationship results in disc degeneration: a condition that can lead to excruciating pain and loss of function, and which often requires costly surgical interventions. Drs. Risbud and Shapiro’s work focuses on determining how disc cells can survive and function in this low oxygen - high osmotic pressure environment using molecular techniques. A second area of study is to elucidate the effect of factors (cytokines) that cause inflammation of the cells that populate the disc. These studies are yielding new insights into the pathogenesis of degenerative disc disease and providing a range of new targets for drugs to prevent and control disc degeneration and back pain.
Anderson, Markova, & Kepler Research
Our laboratory is engaged in elucidating the molecular mechanisms of axial back pain. Although previous work in our laboratory and others has demonstrated cytokine upregulation in degenerative discs, there has been little investigation into whether cytokine levels and inflammatory degenerative changes have clinical relevance. One of the major research interests of our lab is to explore associations between intradiscal cytokine expression levels and clinical outcomes after spinal surgery, particularly with respect to axial neck and low back pain. We have started a tissue library of serum and disc samples from patients undergoing spinal surgery, which can be used to search for associations between laboratory findings and clinical outcomes. We hope this effort will not only validate the importance of laboratory investigations into mediators of disc degeneration but also identify those mediators which seem to be the most specific predictors of clinical outcome.
Another major current research focus of our lab is to determine if co-culture of human mesenchymal stem cells (hMSCs) will prevent human intervertebral disc (IVD) cells from expressing an inflammatory phenotype. Using cells from degenerative discs and cells from healthy discs exposed to an environment that induces degenerative changes, we hope to learn about how hMSCs can be used to temper or reverse disc degeneration.
Our laboratory has an interest in studying gene expression in the local environment after spinal fusion, a critical component for treating many types of spinal disease. We have studied clinically relevant fusion adjuncts such as bone morphogenetic protein (BMP) and other factors that may influence the fusion process, such as Etanercept, a TNF-α inhibitor that slows osteogenic differentiation and mediates bone resorption at high doses. Partnering with a laboratory in Europe, we are also investigating whether Riluzole, a drug used in treating spinal cord injury, has any effect on bone formation, which may influence the success of spinal fusion surgery performed in the course of treating the spinal cord injury.