Sixty-three U.S. and international patents for pseudo-protein biomaterials have emerged from the Ithaca lab of C. C. Chu, the Rebecca Q. Morgan ’60 Professor of Fiber Science and Apparel Design in the College of Human Ecology—just in the past decade. With more patents pending and extensive partnerships with doctors and researchers at Weill Cornell Medical College (WCMC) in New York City, Chu continues to expand the use of biomaterial properties and practicalities in the treatment of wounds, diseased heart valves and blood vessels, bone repair, gene transfection for gene therapy, immunotherapy for cancer patients, and allergy treatment.
The collaborations are helping to bridge the gap between research and medical practice, enabling WCMC doctors to imagine new possibilities for treatment and Chu to test potential uses for his discoveries.
“Each generation of these products offers new applications and better performance than previous ones,” said Chu, one of the founding members of the Biomedical Engineering Program at Cornell. “In my tribe [Chu’s term for his lab] we are never standing still.”
A key driver of Chu’s continued progress is Cornell’s commitment to fostering and funding working partnerships among researchers, especially within biomedical engineering, nanomedicine, and systems biology; diagnostics and experimental therapeutics; global health and infectious diseases; and cancer-related cell biology. These collaborations leverage Human Ecology and WCMC expertise and resources to advance research and development beyond what the traditional “silo” approach can yield.
“Although difficult to coordinate at times,” said Bo Liu, a specialist in vascular disease, “these working relationships provide researchers access to clinical testing, making their discoveries much more translational.”
Vascular grafts deliver drugs
Chu has partnered with Liu to create drug-eluting, biodegradable vascular grafts. Their research is supported by the Morgan Seed Grants for Collaborative Multidisciplinary Research in Tissue Engineering. Liu’s lab provided a clinical outlet for Chu’s biomaterial research, advancing it from traditional material study to small animal testing, a critical first step in the long journey from basic research to clinical practice. The data collected by Liu, now an associate professor at the University of Wisconsin, have helped Chu to significantly advance the performance of biomaterials for cardiovascular treatment.
Vascular grafts have been commercially available for more than 50 years. While effective, these grafts are made of traditional fabrics such as polyesters and Gore-Tex that are non-biodegradable and offer no drug-eluting capabilities. Chu’s vascular grafts, on the other hand, consist of patented amino-acid–based polyester amides (PEA) biomaterials invented in Chu’s lab that are capable of delivering a wide range of bioactive compounds, such as nitric oxide.
Chu said the advantage to human cardiovascular health is that his grafts “biomimic” what the natural blood vessel already does. “Using nitric oxide for the vascular grafts was a natural choice because it is indigenous to the body,” said Chu. “When stimulated, the body produces nitric oxide to dilate the blood vessels along with a host of other critical biological functions, helping to keep them open for optimal blood flow.”
When rat aortic patches were tested in Liu’s lab, the nitric oxide–eluting vascular grafts showed significant advantages over non-eluting grafts, including the ability to promote endothelial cell lining, protect against intimal hyperplasia (the thickening of the vessel wall), and mute inflammation. The Chu lab’s PEA-based biomaterials offer another advantage, thanks to an unusual and unique biological property: muted inflammatory response to foreign bodies. It’s a trait that is unmatched by current FDA-approved biomaterials and their medical devices, Chu said.
Their unique properties allow them to be tailored for many specific clinical applications: as scaffolds for tissue growth and regeneration; as stents for treating cardiovascular diseases; or as delivery vehicles for therapeutic biologics, drugs, or DNA. The biomaterials’ versatility enables Chu to engineer them into fibers, gels, spherical particles (nano or micron size), and fibrous membranes. The diverse applications of these fabricated forms have led Chu into several new partnerships with WCMC scientists working to improve surgical sutures, allergy disease immunotherapy, and prostate cancer treatments.
“Every university should have these types of collaborations,” said Dr. Jason Spector, assistant professor of plastic surgery and director of the Laboratory of Bioregenerative Medicine and Surgery at WCMC. “Every day I see things on the clinical side that need to be improved, but without access to bioengineers, I don’t have the ability or the tools to solve them.”
Chu said the partnerships are mutually beneficial, granting him access to the knowledge and resources to evaluate the biological properties and therapeutic values of his new inventions.
Surgical sutures promote healing
Currently, Spector and Chu are working together to improve the performance of surgical sutures by reducing their foreign-body–induced inflammatory response, which, in turn, can significantly improve the healing process. Commercially available sutures made from natural proteins such as silk and catgut are absorbable by the body but often trigger inflammation due to their foreign protein structure that differs from what the body itself produces. Chu discovered that coating these sutures with PEA-based biomaterials could lead to a dramatic reduction in inflammatory response as shown in an animal coronary artery model.
“One of the many advantages of the PEA is that they are cell, tissue, and blood friendly,” explained Chu. “They are of the body and for the body, which enhances overall acceptance during absorption.”
Spector and Chu are in the midst of testing absorbable sutures in mice in Spector’s lab. Like Chu’s work with Liu, Spector’s and Chu’s collaboration has enabled this new development to move from materials research into animal testing, thereby increasing the probability of it moving into clinical trials.
Microspheres treat allergies
The PEA’s muted inflammatory and drug-eluting properties have also led to a working partnership between Chu and Dr. William Reisacher, assistant professor of otorhinolaryngology and the director of the Allergy Center at New York Presbyterian Hospital/ WCMC. Reisacher developed an innovative method of treating allergies using injections filled with microspheres carrying allergenic proteins. When injected into the body, these microspheres gradually release the proteins over three months, decreasing the frequency and number of allergy shots required by his patients.
For his delivery agent, Reisacher relies on FDA-approved polyglycolic-lactic acid (PGLA), commercially available polymers that have been in use for more than 20 years. They are biodegradable, but trigger an inflammatory reaction in the body. As an alternative, Chu and Reisacher are testing Paclitaxel-loaded PEA microspheres as a delivery agent. These “self-degrading” polymers offer programmable release rates while muting the body’s inflammatory response. Early lab tests have been promising, and the two scientists are now moving the product toward animal testing.
“The clinical needs really drive the further development of these polymers,” said Reisacher. “If you have a wonderful discovery like Chu’s, you also need the clinical perspective provided by these collaborations to know where it can be used.”
Positive polysaccharides kill cancer cells
Chu’s many collaborations with WCMC partners have opened the door for another valuable research opportunity with Dr. David Nanus, the Mark W. Pasmantier Professor of Hematology and Oncology in Medicine and the co-chief of the Division of Hematology and Medical Oncology at WCMC.
During a surgical retreat between Weill and Ithaca-based scientists and engineers supported under the Morgan Tissue Engineering Initiative, Chu learned that cancer cells have more negative charge characteristics on their cell membranes than do normal cells. Through his earlier work on DNA capture and release for the gene transfection study, Chu had developed a novel cationic, water soluble, and nontoxic member of the pseudo-protein family for capturing DNA, which also carries a negative charge. When Chu and Nanus combined efforts with the help of the Seed Grants for Intercampus Collaborative Research Cornell Prostate Cancer Research Group, they discovered that Chu’s newly developed positively charged polysaccharides selectively bound to the negatively charged cell membrane of prostate cancer cells, killing the cancer cells in the process.
Tissue studies conducted by Nanus have confirmed that when certain new polysaccharides developed in Chu’s lab are delivered in specific concentrations, they can indeed selectively kill prostate cancer cells without harming normal cells. “Instead of the indiscriminate killing of cells caused by chemotherapy or radiation,” Chu said, “these tailored-designed polysaccharides at the right dosage appear to selectively attack the prostate cancer cells.”
Chu believes that this new finding may be extended to treat enlarged prostates, though actual clinical use is years away with the need for extensive animal and clinical trials. Nanus and Chu are preparing to publish their findings and hope to complete a more extensive study down the road.
“Publication, patents, and partnerships are the three ‘Ps’ that are the hallmark of my multidisciplinary research program,” Chu said. Each moves Chu’s groundbreaking discoveries one step closer to medical practice, where they can help patients in need of potentially life-saving or therapeutic technologies.