Orthopedics Faculty Receive Research Funding
Several faculty from the Department of Orthopedics and Rehabilitation at the University of Wisconsin School of Medicine and Public Health recently have received funding for research projects.
The investigators and funded projects include:
Wan-Ju Li, PhD, assistant professor, "Blood-Derived Induced Pluripotent Stem Cells for Cartilage Repair"
The objective of this project, funded by the National Institutes of Health (NIH), is to develop an effective tissue engineering therapy for treatment of cartilage lesions caused by injuries or diseases, such as osteoarthritis.
Emerging stem cell-based tissue engineering therapies that provide a biological solution to cartilage degeneration are considered advantageous over existing pharmacological or surgical approaches. While mesenchymal stem cells deriving from adult tissues such as bone marrow or fat are the most commonly used stem cell type in studies to date, the cells have several inherent properties that limit their potential for use in cartilage tissue engineering.
Li and his laboratory recently demonstrated that cell reprogramming technology is able to transform a patient's own peripheral blood mononuclear cells into induced pluripotent stem cells as a robust mesenchymal stem cell source for tissue engineering, which provides an opportunity for the development of personalized medicine for disease treatment.
William Murphy, PhD, professor, "Biomaterials for Local Regulation of Growth Factor Signaling"
Murphy received renewal funding from the NIH for this project, which aims to mitigate the need for expensive and complex biological supplements that currently hinder biomedical applications of stem cells. The resulting approach will be transformative, as growth factor supplements represent the primary driving force for increased cost and regulatory burden in stem cell applications.
Stem cells are emerging as a powerful biomedical tool, and significant applications in drug/toxin screening, disease modeling, and clinical cell therapy are on the horizon. Recent studies have pushed stem cells closer to biomedical applications by improving stem cell "biomanufacturing" processes, including cell expansion, differentiation and tissue morphogenesis.
During the first five years of the award, Murphy and his laboratory established new mechanisms for specific growth factor sequestering. They discovered that biomaterials engineered with biomimetic peptides could regulate specific growth factor signaling in adult cell culture. During the newly funded period Murphy and his team will use their own defined growth factor sequestering concepts to circumvent critical barriers in biomedical applications of stem cells.
William Murphy, "Matrices for Optimal Endogenous Progenitor Cell Recruitment and Function"
NIH funding will be used by Murphy and his laboratory to propose an approach to use synthetic biomaterial arrays to recruit functional circulating angiogenic cells, and thereby enhance neovascularization.
There is a critical need to:
- Systematically explore the biomaterials-associated factors that may be critical to endogenous CAC recruitment, and
- Efficiently discover optimal biomaterials for circulating angiogenic cell recruitment and function
Murphy and his team will use an enhanced throughput approach to discover optimal hydrogels for CAC recruitment and sustained function. These studies will provide a basis for a larger research program to elucidate the mechanisms of endogenous cell recruitment and circulating angiogenic cell-mediated angiogenesis in vitro and in vivo.
Geoffrey Baer, MD, PhD, associate professor; and Connie Chamberlain, PhD, research scientist, "Genetically Modified MSCs to Explain Their Anti-Inflammatory Role in Regenerative Tendon Healing"
Ligament and tendon injuries are common clinical problems that often result in scar formation and failure to restore the composition and mechanical properties of native tissue. In this study, funded by the Orthopedic Research and Education Foundation, Baer and Chamberlain will use transgenic mesenchymal stem/stromal cells as a novel delivery method to investigate specific inflammatory factors on tendon healing.
This approach provides a variety of potential clinical applications extending from the proposed studies, as the strategy for gene delivery is highly adaptable. Insight from these studies will elucidate mesenchymal stem/stromal cell therapy as well as optimize immunomodulation during healing, which will ultimately facilitate more consistent beneficial clinical outcomes.
Alison Brooks, MD, MPH, assistant professor, Funding to Study Concussions
Brooks recently received funding from the landmark $30 million NCAA-U.S. Department of Defense Grand Alliance, which is funding the most comprehensive study of concussion and head impact exposure ever conducted.
The Concussion Assessment, Research and Education (CARE) consortium will enroll an estimated 25,000 male and female NCAA student-athletes over a multi-year study period. Brooks and her team participate in two cores:
- Longitudinal Clinical Study Core (CSC): The Longitudinal Clinical Study Core, led by the University of Michigan, is a prospective, multi-institution clinical research protocol that aims to study the natural history of concussion among NCAA student-athletes. This investigation will be the largest ever of its type. Brooks and her team are participating in year two of this core.
- Advanced Research Core (ARC): The Advanced Research Core, led by the Medical College of Wisconsin, includes cutting-edge studies that incorporate head impact sensor technologies, advanced neuroimaging, biological markers, genetic testing and detailed clinical studies to examine the acute effects and early pattern of recovery from sport-related concussion. Ultimately, the work is designed to more fully inform a comprehensive understanding of sport-related concussion and traumatic brain injury. Brooks and her team are in their first year of participation in the ARC.
Warren Dunn, MD, associate professor, "Revision ACL Reconstructions: A Comparative Effectiveness Treatment Study"
Dunn received a new round of NIH funding for this study led by Washington University in St. Louis. This project's goal is to elucidate the factors responsible for success or failure of ACL revision surgery. This study has enrolled 1,200 subjects who have undergone a revision ACL knee reconstruction, and will longitudinally follow this cohort at two, six and 10 years using an initial validated outcome questionnaire, as well as determine the incidence of clinical graft and/or contralateral ACL failure.
Bryan Heiderscheit, PhD, professor, Funding to Study Gait Analysis
Heiderscheit received funding from Metria Innovation to participate in the second phase of a study to develop and validate an instrumented gait analysis system and associated training and reporting tools.
Gait dysfunction can dramatically affect a person’s ability to perform activities of daily living, and assessment of gait is a critical component of physical therapy practice.
John Wilson, MD, MS, associate professor, “The Clinical, Biomechanical, and Tissue Regenerating Effects of a Single PEAK Platelet-rich Plasma Injection for the Treatment of Chronic Lateral Epicondylosis: A Randomized Controlled Trial”
With funding from DePuy Synthes, Wilson will evaluate the clinical, biomechanical and tissue regenerating properties of a single platelet-rich plasma injection for common extensor tendinosis. Post-injection imaging will be compared with pre-injection imaging to assess whether a single injection of platelet-rich plasma has any effect on tendon healing and mechanics. The correlation between imaging outcomes and clinical scores will also be examined.
The results of this study may lead to larger, randomized controlled trials evaluating the clinical and radiographic outcomes of platelet-rich plasma for the treatment of chronic lateral epicondylosis.
Date Published: 02/22/2016