Philadelphia University + Thomas Jefferson University

Laboratories

PIortho

The Laboratory of Theresa Freeman, PhD:  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.

Contact Information: 

Theresa.Freeman@jefferson.edu or (215) 955-1068


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The Laboratory of Noreen Hickok, PhD: 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 show great potential in combating these devastating infections.

Contact Information:

Noreen.Hickok@jefferson.edu or (215) 955-6979


The Laboratory of Rowena McBeath, MD, PhD: 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 re-engineered tendon will be used in a rabbit model of tendon regeneration prior to being assessed for a clinical study in humans.

Contact Information:

Rowena.McBeath@jefferson.edu or (215) 521-3003


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The Laboratory of George Feldman DMD, PhD: Developmental Dysplasia of the Hip (DDH), a debilitating condition characterized by incomplete formation of the bones of the hip joint, can lead to dislocation of the femur, and crippling arthritis. Current research is aimed at identifying the mutation(s)  and develop a diagnostic DNA test to identify individuals at risk for this disorder. Dr. Feldman studying the DNA of a four-generation family have found a potentially harmful mutation in the gene encoding an important cell receptor (CX3CR1). In another family, a second potentially harmful mutation was found in the teneurin3 gene.   Both of these DNA changes are thought to delay the maturation of stem cells in forming the cartilage of the hip bone.  Identification of these mutations may lay the foundation for an accurate diagnostic test in newborn while treatment of DDH would prevent hip dysplasia from developing into osteoarthritis.

Contact information:

George.Feldman@jefferson.edu or (215) 573-1514


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The Laboratory of Andrzej Fertala, PhD, Professor of Orthopaedic Surgery: Fibrosis, is a condition which 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 which include 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.

Contact information: 

Andrzej.Fertala@jefferson.edu  or (215) 503-0113


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The Laboratory of Makarand V. Risbud, PhD, and Irving M. Shapiro, BDS, PhD: 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 provide 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 focusses 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.

Contact information:


The Laboratory of David G Anderson MD, Dessislave Markova, PhD, and Christopher Kepler MD: 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 which 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 which may influence the fusion process such as Etanercept, a TNF-α inhibitor which 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.

Dessislava.Markova@jefferson.edu or (215) 955-7655


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The Laboratory of Ryan Tomlinson, PhD: Skeletal fracture is one of the most prevalent and costly medical issues in the United States, with direct costs exceeding $20 billion annually. In fact, some studies have shown that women over the age of 75 would rather be dead than suffer the consequences of a hip fracture. As a result, the overall goal of the Tomlinson lab is to develop novel approaches to augment bone strength and prevent painful and debilitating fractures. Previous studies has shown that bone is continually sensing and converting mechanical cues into biochemical signals, which subsequently direct and mediate both anabolic and catabolic processes in the skeleton. Although the detection of forces in the skeleton has traditionally been attributed to osteocytes, recent work has shown that sensory nerves, which blanket the surfaces of bone in a mesh-like network, also contribute to skeletal adaptation. Nearly all of these nerves express TrkA, the high affinity receptor for nerve growth factor (NGF). Previous studies identified a critical role for NGF-TrkA signaling in skeletal development, during which osteochondral progenitors express NGF to coordinate the innervation, vascularization, and ossification of long bones. Furthermore, NGF was shown to be robustly expressed in adult bone by mature osteoblasts in response to non-damaging mechanical loads. In that study, inhibition of NGF-TrkA signaling impaired load-induced bone formation whereas administration of exogenous NGF increased relative bone formation rates. In on-going work, our lab is identifying sensory-nerve derived osteogenic cues downstream of NGF-TrkA signaling. By characterizing the role of sensory nerves in bone, we hope to identify new methods for reducing overall fracture risk in humans. tomlinsonlab.com

Ryan.Tomlinson@jefferson.edu or 215-955-5504