With an $11 million grant from the National Institutes of Health Center for Biomedical Research Excellence, Clemson University has launched the South Carolina Center for Translational Research Improving Musculoskeletal Health, or SC-TRIMH, a new research center that will bring together scientists from across South Carolina to change the way musculoskeletal disorders are diagnosed, treated and even studied.
The award was announced Thursday at a meeting of the Clemson University board of trustees. SC-TRIMH is Clemson's third COBRE-funded center; since 2009, Clemson has received more than $40 million in COBRE funding.
Led by bioengineers at Clemson, SC-TRIMH combines orthopedics and other clinical expertise from the Greenville Health System and the Medical University of South Carolina with computer scientists, computational engineers, biophysicists and other experts to better understand musculoskeletal disorders and to design and evaluate new devices, interventions and drug therapies.
Disorders affecting bones and joints - including arthritis, osteoporosis, chronic back pain and sports injuries - are the leading cause of disability and a major driver of health care costs around the world, especially as the population ages and particularly among poor people. A recent national report showed that one in two American adults have a musculoskeletal problem, with a price tag of nearly $1 trillion in 2014. By 2040, more than one-quarter of Americans - 78 million - will receive a diagnosis of arthritis, according to the Centers for Disease Control and Prevention.
"Thanks to the talent and determination of Clemson faculty, students and staff, and to our invaluable partnerships with GHS and MUSC, South Carolina is leading this exciting new fight against one of the most significant problems facing Americans and American health care," said Clemson University President James P. Clements. "We are grateful that the NIH has once again acknowledged Clemson University as a leader in academic research, and we look forward to working with our partners to advance innovation and clinical care."
"By working together, we can significantly improve health care and health outcomes in South Carolina and the nation," said Spence Taylor, president of Greenville Health System and himself a vascular surgeon. "These innovative partnerships between Clemson faculty and GHS clinicians allow us to solve clinical challenges by leveraging medical insights with the extraordinary research depth of Clemson. What we do today can pave the way for transformational improvements to health care for generations to come."
"Our team looks forward to deepening our long-standing relationship with Clemson and searching for next-level innovations through this COBRE grant," said MUSC President David J. Cole. "The challenges we face today in the health care domain are bigger than any one entity can solve. It is only through strategic partnerships based on shared vision and collective effort that we can leverage the strengths and capabilities of our individual institutions to successfully move into the future."
Revolutionizing testing
A major component of SC-TRIMH is the creation of "virtual clinical trials" to reduce the time it takes novel ideas to go from concept to clinical practice, thereby reducing costs while improving care.
Currently, only about 10 percent of new discoveries find their way into practice within 20 years, due in part to a gap in the clinical trial process, in which innovations go through extensive animal testing before they're attempted in humans.
"While the current clinical trial process tells us that a product is unsafe or ineffective, they rarely tell us why or suggest how to improve it," said Hai Yao, Ernest R. Norville Endowed Chair and professor of bioengineering at Clemson University and the administrative leader of the center. "This results in an all-or-nothing mindset in the biomedical industry, which stifles innovation and reduces the number of truly original biomedical projects available to surgeons while increasing costs."
The virtual clinical trial will fill that gap. It's akin to very detailed, very personalized flight simulator training for musculoskeletal diseases. Scientists working in SC-TRIMH will build computer simulation models based on patient data, from the cellular pathology of a disease to how the person's bones and joints move under various scenarios. If the patient needs a hip replacement, surgeons can test various implants in the computer model under different conditions before it's implanted in the patient.
By constructing very specific models of each step at the body, tissue and molecular scales, the scientists will build a catalog of predictive models that can be used in research, thereby creating a continuous loop of data that will improve innovation.
With Clemson's rich history in bioengineering and orthopaedic engineering research - establishing one of the first academic departments in the country, playing a major role in creating the Society of Biomaterials and its faculty and students inventing many biomedical advances and devices - SC-TRIMH will also dedicate resources to finding commercial opportunities to make sure innovations are widely available, said Martine LaBerge, professor and chair of the bioengineering department, which recently was ranked fourth in the country for value.
Key partnerships and resources
Several factors position SC-TRIMH to revolutionize clinical trials; chief among them are long-standing collaborations between Clemson and its major health systems partners. Finding, facilitating and nurturing partnerships is the role of the Clemson University School of Health Research (CUSHR), led by Windsor Sherrill, associate vice president for health research and the chief science officer at GHS. CUSHR places the university's basic scientists and engineers with physicians and other biomedical scientists.
In 2011, Clemson and GHS partnered to open a laboratory, surgical training and innovation space called the Clemson University Bioengineering Innovation Center at the hospital system's Patewood campus in Greenville, South Carolina, in the same building with clinical orthopedics, vascular surgery and imaging. In 2003, the Clemson-MUSC Bioengineering Program opened at the MUSC campus in Charleston, with Yao (the associate chair for the program) and other faculty stationed there full time.
Other key resources are:
- Supercomputing cyberinfrastructure, namely the Palmetto Cluster, which places Clemson fourth among all public universities in the United States in supercomputing capacity;
- Predictive computational modeling, building on the experience of the Institute for Biological Interfaces of Engineering at Clemson;
- Advanced design, 3-D modeling and rapid prototyping of patient-specific devices in the labs of Georges Fadel in the Clemson Engineering Design Application and Research Center;
- Miniaturized smart sensors for biomedical applications that will enable the testing of prototypes, led by Hai Xiao;
- Expertise in animal models, led by Jeryl Jones; and a human cadaver lab, led by GHS orthopedic surgeon Michael Kissenberth, in the CUBEInC facility.
Three core facilities will be created based on these resources: multiscale computational modeling, led by Hai; advanced fabrication and testing, led by Xiao and Fadel; and, at GHS, pre-clinical assessment, led by Jones and Kissenberth.
Investing in the future
The COBRE grant also funds a pipeline of basic scientists to tackle fundamental questions about musculoskeletal disorders. Five Clemson junior researchers were chosen for positions to be supported by the grant for a maximum of three years, by which time they are expected to apply for and receive their own senior-level funding from the NIH. When a junior researcher "graduates," a new one is chosen in their place.
As a result, Clemson will produce a cascade of new knowledge and untold educational opportunities for undergraduate and graduate students, and new lab technician positions, LaBerge said.
"The SC-TRIMH initiative has potential to enable truly transformative research by connecting Clemson researchers to our GHS orthopedic researchers," said Michael Kissenberth, an orthopedic surgeon at GHS who, along with Kyle Jeray, chair of GHS' orthopaedics department, will lead the clinical advisory committee for the program. "Clinical perspective will inform the work of each junior investigator. So often, this is a missing element in health research. With SC-TRIMH and the Clemson University School of Health Research, we are establishing a new approach to investigating musculoskeletal health. This is a wonderful chapter in orthopedic research at GHS and for South Carolina."
Each of the original cadre of junior researchers has either already received independent funding or is very close.
The original researchers are:
- Hugo Sanabria, a biophysicist, who is using multiscale modeling to uncover the structure, dynamics, and functional relationship of osteoclast-specific V-ATPases in order to design better therapeutic approaches for osteoporosis.
- William Richardson, who is investigating unknown mechano-sensitivities of the collagen-MMP-growth factor network, and he is developing a computational model for screening potential therapeutic interventions for tendons under diverse loads.
- Tong Ye, who is using two-photon excitation fluorescence and second harmonic generation to evaluate cell and matrix changes of cartilage during tissue remodeling to develop needle endoscopy probes with an imaging system to assess cartilage repair in vivo.
- Melinda Harman, who is developing a novel way to determine the tension profiles of soft tissues crossing the knee joint to improve knee replacement design and to define a predictive pre-clinical test protocol for prospective total knee replacement designs.
- Fei Peng, who is developing embedded, micro-wireless strain sensors for hip joint replacement to understand the effect of surgery factors, such as the positioning and choice of implants, on total hip arthroplasty.
In 2009, a $9 million NIH COBRE program grant funded the South Carolina Center for Bioengineering Center for Regeneration and Formation of Tissues (SC BioCRAFT). In 2014, SC BioCRAFT received a renewal award of an additional $11 million. The center has produced more than 300 scientific publications, filed 45 patents, and has received more than $20 million in external funding.
In 2016, a $10.5 million COBRE grant funded the Eukaryotic Pathogens Innovation Center (EPIC). Since the award, EPIC investigators have generated more than $4.5 million in external funding and produced 35 publications. In addition, EPIC secured the first ever NIH training grant at Clemson.
Professor Nancy Ip: Pioneering New Paths in Neurodegenerative Therapy