More than skin deep: Chih-Chang "C.C." Chu is working with Cornell researchers in the engineering and medical colleges to develop artificial skin, heart valves, and blood vessels.
Subject: College teachers (Beliefs, opinions and attitudes)
College teachers (Practice)
Cardiovascular diseases (Care and treatment)
Biomedical engineering
Author: Wheatley, Claudia
Pub Date: 11/01/2008
Publication: Name: Human Ecology Publisher: Cornell University, Human Ecology Audience: Academic Format: Magazine/Journal Subject: Health; Science and technology; Social sciences Copyright: COPYRIGHT 2008 Cornell University, Human Ecology ISSN: 1530-7069
Issue: Date: Nov, 2008 Source Volume: 36 Source Issue: 2
Topic: Event Code: 200 Management dynamics
Persons: Named Person: Chu, Chih-Chang; Chu, Chih-Chang
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 231021637
Full Text: For years researchers have been trying to develop a high-functioning artificial artery that the human body will accept as its own. The realization of this medical dream may be one step closer, thanks to the pioneering work of College of Human Ecology professor Chih-Chang "C.C." Chu and a Morgan Seed Grant for Collaborative Mnltidisciplinary Research in Tissue Engineering.

"To create the perfect artery that could be taken off the shelf and sewn into patients would have a tremendous impact on the longevity and quality of life for patients all around the world," said vascular surgeon K. Craig Kent.

Cardiovascular disease affects more than 80 million Americans and accounts for one in three deaths each year. Most patients die because of atherosclerosis, in which arteries clogged by fatty plaques aren't able to maintain adequate blood supply to vital organs like the heart, brain, or kidneys. Negative outcomes, though, can be avoided if the disease is treated before it does irrevocable damage.

Current treatment involves forcing the affected artery open (angioplasty) followed by the placement of a metallic stent or replacing it with an artificial graft or one of the patient's own veins. But artificial arteries are subject to blood clotting and don't function very well, particularly in small diameter vessels like the ones in the heart and below the knee. As many as 50 percent of patients don't have healthy veins to spare--and all three approaches could lead to restenosis, when the affected blood vessel narrows all over again.

As a member of the Weill Cornell Medical College faculty, Kent became interested in the university's efforts to build partnerships between researchers on the Ithaca and New York City campuses. In particular, he was intrigued by an incentive called the Morgan Seed Grant for Collaborative Multidisciplinary Research in Tissue Engineering. A gift of Jim and Becky Morgan, graduates of Cornell's engineering and human ecology colleges, respectively, the program supports the start-up efforts of researchers from both colleges and the medical school who pool their expertise to develop new solutions to medical problems.

"The number one reason we are funding the projects is to encourage collaboration between and among the colleges within the university," said Becky Morgan. The second reason--and the impetus for championing tissue engineering--is very personal: the Morgans' granddaughter was born with a giant nevus--a blemish that can lead to skin cancer--that covered more than one-third of her back. Nevi can be surgically removed, but extensive skin grafts are often needed to cover the excision site, and the options for skin grafts are limited.

"It's my hope that between biomedical engineering and the kinds of things that C.C. Chu and others at [the College of Human Ecology] are doing that we might find a new remedy," said Morgan.

Indeed, one of the eight projects receiving seed grants is an effort to develop bioengineered skin tissue that will heal faster and better than current commercial products.

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Of the eight projects, three are dependent on the work of Chu, the Rebecca Q. Morgan '60 Professor of Fiber Science & Apparel Design. Chu is a preeminent researcher in the world of biodegradable biomaterials and tissue engineering, and the holder of more than 50 U.S. and international patents stemming from his work.

Biodegradable biomaterials developed in Chu's lab have applications for the treatment of wounds, diseased heart valves and blood vessels, bone repair, gene transfection for gene therapy, and even immunotherapy for cancer patients. And if one of his Morgan seed grant projects is successful, Kent and his colleagues could be one step closer to their colleagues' wish for an off-the-shelf replacement for blocked arteries.

A meeting of minds

With the Morgan seed grant in place, the College of Human Ecology, along with the Department of Biomedical Engineering in the College of Engineering and the Department of Surgery at Weill Cornell College of Medicine, held several retreats where researchers from the Ithaca and New York City campuses described their work and the kinds of collaboration they were looking for. Grant proposals were rated by outside reviewers with national and international reputations in tissue engineering.

"We were interested in scientific merit and synergism between disciplines," said Kay Obendorf, senior associate dean of research and graduate education and a professor of fiber science and apparel design. "The teams came together extremely easily, and the synergism seemed to be there from the first time we got them together."

Kent and his associate Bo Liu, associate research professor of cell biology in surgery, found a good match with Chu. "He had developed these really fascinating polymers, and we had intense interest in arteries, in vascular biology," said Kent. "He was just what we needed, and we were just what he needed, to bring this all together."

"My research focuses on the treatment of life-threatening diseases and accidents through the lens of biomaterials and medical devices, and it's naturally multidisciplinary," Chu said. "I have worked on biodegradable biomaterials since I came to Cornell in 1978. At that time I could count on the fingers of one hand how many people in the United States were working in this area. Now I need to borrow everybody's fingers and toes to count them. It was really unusual for the college and the Department of Fiber Science & Apparel Design to see that this was a direction they wanted to move into. It took a lot of courage and risk by my former colleagues to move into this little-known frontier back in the 1970s. The college and department are decades ahead of their peers and are really one of the few pioneers in the field of biodegradable biomaterials for human body repair."

Chu completed the vascular graft team with Cynthia Reinhart-King, assistant professor of biomedical engineering in the College of Engineering, whose research focuses on endothelial cells, which line the insides of blood vessels. "Our skill sets are really a perfect match," said Reinhart-King. "He's a great materials guy, and my expertise is in cell adhesion, particularly the cells that comprise blood vessels."

The team's goal is to replace an artificial artery that's been in use since Michael DeBakey developed it in 1958. Chu hands over a commercial graft sample: it looks like a miniature Slinky covered with Gore-Tex. It's made by conventional textile milling," he said. "The body will try to react to it--it's a foreign material--and the healing will never be complete, and blood clotting will set in. That's why patients have to take anti-clotting medicine. It can't be used to replace narrower arteries, such as those located below the knee or in the heart. And the materials used in artificial grafts are not biodegradable. Once implanted, they remain in the body permanently."

The Cornell group's vascular graft project is designed to be biologically active and temporary; to act as a scaffold to which blood vessel cells will adhere, ultimately regenerating a new, natural artery. The graft, being biodegradable, would eventually be absorbed by the body. The new biodegradable graft biomaterial would also be biologically active, which means it could actively participate in the wound healing of the graft after surgery.

The materials used to build that scaffold are derived from a family of amino acid-based polymeric biomaterials developed in Chu's lab in early 2000 that are called polyester amides (PEA). Chu's lab has successfully engineered and fabricated these PEAs into an astonishing array of purposes. They can be fabricated into fibers; 3-D microporous gels; micro- and nanospheres; or electrospun fabric membranes; they can be positively, negatively, or neutrally charged; they can be hydrophilic or hydrophobic.

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Chu runs through some slides of PEA projects in progress. "We developed this drug-eluding fibrous membrane and Weill Cornell surgeons implanted it into a pig for a second-degree burn trial. It worked out beautifully and healed wound tissue faster and better than a commercial product. Here is another new one for bone generation. The device in this image is a drug-eluding stent that Cornell licenses to a company to develop biodegradable coatings. This new gel biomaterial is intended to carry interleukin 12 for immunotherapy of cancer, and can be engineered to carry vaccines and cells, too. I envision that these biodegradable 3-D microporous gels may be able to serve as a scaffold for cells to grow into tissues in the future."

He finds the slides for the artery project. "This tubular graft biomaterial has a nitric oxide derivative," Chu explained. Nitric oxide keeps a natural blood vessel dilated. An artificial blood vessel that has built-in nitric oxide could have the potential to ward off restenosis.

"C.C.'s PEA polymer is elastic, in the way that blood vessels are elastic," said Reinhart-King. "Most grafts and stents fail because the elasticity of the blood vessel doesn't match the elasticity of the graft, and that can cause the blood vessel to occlude. C.C.'s polymer looks like it might be ideal for the situation."

Of the eight projects receiving Morgan seed grants, Chu is applying his PEAs to three: one for developing artificial skin, one to produce artificial heart valves, and the blood vessel project.

"We hit the jackpot when we discovered them," said Chu. "This new family of biodegradable PEA biomaterials might eventually replace the commercial biomaterials introduced in the 1970s."

The power of partnerships

For Kent and Chu, one good collaboration led to another. "He started wondering if the same polymer could allow genetic material to enter cells--human gene therapy--and we have tremendous experience with gene therapy because that's one of the things we do in our lab," said Kent. "So once there was some synergy and symbiosis, we ended up with two different projects."

According to Chu, his research has "three Ps"--publications, patents, and partnerships--and the gene therapy project best exemplifies his approach. "The partnership with Kent's group has led to a joint patent application and joint publications between the Ithaca and Weill campuses," he said.

"We're fortunate that the university is making a strong effort to tie the two campuses together, and we've found the clinicians down there extremely interested in collaborating," said Reinhart-King. "Mostly because of enthusiasm for the projects, things are going well."

Kent agrees. "Medical schools and graduate and undergraduate schools don't collaborate that much, yet when they do, the potential benefits to medical research are tremendous," he said. "Someone has to have the foresight to create the ability for partnerships to be formed, and that was accomplished very successfully in our case."

Seed grants are "extremely important in stimulating research," said Reinhart-King. "These collaborations probably wouldn't have occurred without the Morgan seed grant."

Chu is more emphatic. "If you don't have a dedicated funding source, everybody does collaboration on an ad hoc basis, and it drags and goes nowhere," he said firmly. "We don't have the resources or time to divert to something we're not responsible for. We need a catalyst to get us started. These eight projects--none of them would happen if we didn't have the Morgan seed grant. None of them."

"I am thrilled with the response of the three deans and the assigned professors; with their enthusiasm and support of the collaborations," said Morgan. A major in textiles and clothing, the precursor to fiber science and apparel design, she's seen the department evolve in ways she never would have imagined as an undergraduate. "Fibers are a new way of solving problems," said Morgan. "New kinds of fibers, new uses; I think it's terribly exciting."

For Chu, the excitement lies in the development of new knowledge that could have tangible results that will help people. "That is what human ecology is about--dealing with human beings inside and out. We will never be able to see that if we just publish a paper and say 'That's it'," said Chu. "That's the beauty of this college and this type of multidisciplinary research; in addition to advancing knowledge, we could have real products that benefit real people. If you live long enough, you may benefit from what we're doing here.

RELATED ARTICLE: Morgan Seed Grant Projects

To date, eight projects have received funding through the Morgan Seed Grant Program. Project objectives range from developing models to aid understanding of disease processes to synthesizing skin, cartilage, and even blood vessels to repair the ravages of disease.

Engineering Physiological Distributions of Zone-Specific Phenotype and Fiber Orientation in a 3-D Tissue Engineering Cartilage Scaffold

Objective: To make tissue-engineered cartilage, a key opportunity for the treatment of arthritis. The approach could be used on a wide variety of other tissues as well.

Faculty investigators

Brian Kirby (Engineering), Principal; investigator

Margaret Frey (Human Ecology)

Juan Hinestroza (Human Ecology)

Lawrence Bonassar (Engineering)

Fibers-Reinforced Tissue Scaffolds with Microfluidic Vascular Templates for Wound Repair and Reconstructive Surgery

Objective: To build scaffolds that will promote development of replacement tissue that is immunocompatible, versatile, cost effective, mechanically robust, and maintains its volume and function over time.

Faculty investigators

Abraham Strook (Engineering), Principal investigator

Lawrence Bonassar (Engineering)

Margaret Frey (Human Ecology)

Jason Spector (Weill Cornell Medical College)

A Multidisciplinary Approach for Engineered Heart Valves Using Novel Biomaterials

Objective: To engineer a living heart valve replacement that can grow and integrate with patients--a critical need that non-living prosthetic valves are incapable of meeting.

Faculty investigators .

Jonathan T. Butcher (Engineering), Principal investigator

C.C. Chu (Human Ecology)

Leonard Girardi (Weill Cornell Medical College)

Hod Lipson (Engineering)

A Novel Approach For the Prevention of Post-Operative Seroma: Electrospun Polymeric Bioadhesives

Objective: To develop a new bioadhesive that can safely and effectively prevent the accumulation of serum in a tissue or organ and the accompanying swelling, which often occurs following surgery.

Faculty investigators

David Putnam (Engineering), Principal investigator

Margaret Prey (Human Ecology)

Jason Spector (Weill Cornell Medical College)

Novel Biodegradable Scaffolds for Tissue Engineering of Blood vessels

Objective: See main article.

Faculty investigators

C.C. Chu (Human Ecology), Principal investigator

Cynthia Reinhart-King (Engineering)

Bo Liu (Weill Cornell Medical College)

K. Craig Kent (Weill Cornell Medical College)

A Novel Growth Factor and Matrix Mimetic-Enhanced Biodegradable Scaffolds for Skin Tissue Engineering

Objective: Develop a new type of biodegradable tissue-engineered skin substitute.

Faculty investigators

Moonsoo Jin (Engineering), Principal investigator

C.C. Chu (Human Ecology)

Roger Yurt (Weill Cornell Medical College)

Tissue-Engineered Constructs for the Study of the Mechanical Basis of Atherosclerosis Progression

Objective: To create artificial vascular tissue and to use this model system to identify the mechanical mechanisms underlying blockage or enlargement of arteries.

Faculty investigators

Cynthia Reinhart-King (Engineering), Principal investigator

Margaret Frey (Human Ecology)

Ageliki Vouyouka (Weill Cornell Medical College)

Tissue-Engineered Microenvironmental Niches to Study Human Neural Stem Cell Behavior

Objective: to build detailed 3-D models of tissue based on neural stem cells to better understand the origin of brain tumors.

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Faculty investigators

Claudia Fischback-Teschl (Engineering), Principal investigator

Margaret Frey (Human Ecology)

John Boockvar (Weill Cornell Medical College)

The Cornell Center for Technology Enterprise and Commercialization has filed two U.S. patent applications and two new invention disclosures based on C.C. Chu's Morgan Seed Grants.

For more information:

Chih-Chang "C.C." Chu

cc62@cornell.edu

K. Craig Kent

kckent@med.cornell.edu

Kay Obendorf

sko3@cornell.edu

Cynthia Reinhart-King

cak57@cornell.edu
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