Tissue and Cellular Engineering

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Nicholas Hopkins
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Tissue and Cellular Engineering Working with biological materials, Purdue researchers are

Each year, 15 million older men and women begin to lose their vision from age-related macular

To date, the war against this condition has been waged by medical doctors whose primary weapons

surgery. Although these procedures sometimes arrest AMD, they fail to restore lost vision.

areas Tissue and Cellular Engineering (TCE) engineers are joining doctors to help older people

Albena Ivanisevic, an assistant professor in both biomedical engineering and chemistry, is one of

1 Tissue and Cellular Engineering Working with biological materials, Purdue researchers are engineering better health at the cutting edge of tissues and cells. Each year, 15 million older men and women begin to lose their vision from age-related macular degeneration (AMD), a deterioration of tissues in the region of the retina where vision is sharpest. Despite decades of research, the physiological or environmental causes of this condition remain unknown, and there is no cure. Macular degeneration is the leading cause of legal blindness in people over age 55. To date, the war against this condition has been waged by medical doctors whose primary weapons have been nutritional intervention, laser photocoagulation, photodynamic therapy, and macular surgery. Although these procedures sometimes arrest AMD, they fail to restore lost vision. But thanks to a growing interdisciplinary field that Purdue has made one of its eight signature areas Tissue and Cellular Engineering (TCE) engineers are joining doctors to help older people retain or even regain their eyesight. Albena Ivanisevic, an assistant professor in both biomedical engineering and chemistry, is one of Purdue s young research stars in the field, and she s working to bring retinal cell implantation and new hope to AMD sufferers. One potential treatment for macular degeneration is the implantation of retinal pigment epithelial (RPE) and iris pigment epithelial (IPE) cells, says Ivanisevic. But implantation is more successful if some sort of a scaffold is used. Eight Signature Areas Infinite Possibilities 21

SURF s Up: In the summer of 2003, Purdue Engineering hosted more than 40 undergraduates from various schools in the Summer Undergraduate Research Fellowships (SURF), sponsored by the National Science

That s where Ivanisevic s research which blends traditional areas of science and engineering comes into play.

2 SURF s Up: In the summer of 2003, Purdue Engineering hosted more than 40 undergraduates from various schools in the Summer Undergraduate Research Fellowships (SURF), sponsored by the National Science Foundation. Here, Nicole Onyeneho, from the University of Maryland, dissects a canine eye to obtain retinal samples in Albena Ivanisevic s lab. That s where Ivanisevic s research which blends traditional areas of science and engineering comes into play. She is developing scaffolds of biomaterials on which new RPE and IPE cells can grow before being implanted. The scaffolds must be compatible with the surrounding environment and provide adequate cell proliferation, ease of handling, durability, and longevity. Neither bioscaffolds nor biomedical engineering is new at Purdue. What is new is the university s initiative to integrate engineering and the life sciences and to invest heavily in personnel and resources to make Purdue a worldwide leader in the field of tissue and cellular engineering. Beneath the umbrella of bioengineering design at the tissue, cellular, and molecular levels, Purdue will focus on research and development in various subareas: Real-time sensing and imaging of the structure, function, and dynamic characteristics of biological systems; Probing and sensing the functions of and interactions between tissues, cells, and molecules; and Engineering replacement tissue scaffolds with unique mechanical properties based on molecular design. According to Klod Kokini, the TCE co-chair and a professor in mechanical engineering and biomedical engineering, tissue and cellular engineering has emerged as a distinct field in the context of treating and curing bodily damage and injuries. 22 Purdue s Engineering Edge

Many of the key challenges are related to soft tissues, ligaments, and skin, Kokini says. Tissue engineering looks to allow repair of these structures.

Ultimately the hope is to actually grow organs or allow the body to grow organs, Kokini says, although he concedes that such applications are years away.

3 Many of the key challenges are related to soft tissues, ligaments, and skin, Kokini says. Tissue engineering looks to allow repair of these structures. However, regrowing damaged knee cartilage for injured athletes or implanting retinal tissue for patients with macular degeneration may be just the tip of the iceberg of possibility. Ultimately the hope is to actually grow organs or allow the body to grow organs, Kokini says, although he concedes that such applications are years away. The concept at this time is to develop materials by understanding the environment they are in, the relationship between these materials with cells and tissues in the body itself, and to engineer devices and systems that can be used as replacements for tissues. We also look at the relationship between the materials and the cells, which is the critical part of making tissues. Imitative Design: Albena Ivanisevic (standing), an assistant professor in biomedical engineering and chemistry, works with Ph.D. student Youngnoum Cho to develop nanometer resolution lithographic approaches to fabricate biomimetic templates and scaffolds. Kokini s research interests include the mechanical behavior, design and remodeling of biological tissues, as well as the effect of stresses on remodeling and the interactions between cells and extracellular matrices. He collaborates with Sherry Voytik-Harbin, a biomedical colleague who is also a professor of basic medical sciences, and Paul Robinson, a professor of basic medical sciences and veterinary medicine. Tissue and cellular engineering is interdisciplinary by nature. At the molecular and cellular level we need tremendous engineering, yet the engineers also must understand the biological aspects of their work especially about how the cells and tissues of the body react to the presence of an engineered tissue, says Kokini. According to TCE co-chair George Wodicka, the head of biomedical engineering Eight Signature Areas Infinite Possibilities 23

and a professor of electrical and computer engineering, the history of the field illustrates the necessity of combining expertise from both engineering and science.

4 and a professor of electrical and computer engineering, the history of the field illustrates the necessity of combining expertise from both engineering and science. Multidisciplinary Effort: Tissue and cellular engineering is interdisciplinary by nature. Sherry Voytik-Harbin, an assistant professor in biomedical engineering and basic medical sciences, works with Beverly Waisner, a basic medical sciences technician, and Nate Hammond, a biomedical engineering Ph.D. student, in the Tissue Engineering Lab. In order to develop replacement tissues, the mechanical properties of those tissues are vitally important how the properties change when the device is being constructed or once it has been implanted, he explains. These issues are critical in terms of functionality of a device itself, so mechanical engineering principles have been key to this field from the beginning. On the other hand, replacement tissues for nerves raise a different set of concerns. In addition to the mechanical components, Wodicka says, the electrical properties of the replacement tissues need to be fully understood. That brings in the whole realm of electrical engineering. The science factor in the equation bears on issues such as tissue function, cellular interactions, and subcellular 24 Purdue s Engineering Edge

phenomena that affect how replacement tissues are recognized by the body and how cells react to them. In summary, says Wodicka, This area was grown out of both engineering and science.

internationally: The potential to help large numbers of people; Growing interest among faculty members and students; Opportunities for sponsored funding from federal agencies; Clearly defined needs

5 phenomena that affect how replacement tissues are recognized by the body and how cells react to them. In summary, says Wodicka, This area was grown out of both engineering and science. Wodicka and Kokini agree that several factors have converged to push TCE into its signature area position at Purdue and push Purdue into a potential leadership position nationally and internationally: The potential to help large numbers of people; Growing interest among faculty members and students; Opportunities for sponsored funding from federal agencies; Clearly defined needs of industrial partners; The geographic location of several partners in Indiana, which makes for a natural relationship; The reputation of Purdue Engineering and its recent success in biomedical research and development; and Tissue Mechanics: Alaina Pizzo, a Ph.D. student in mechanical engineering co-advised by Professors Klod Kokini and Sherry Voytik Harbin, integrates her knowledge of engineering and life science to study the mechanical properties of tissues and cells. The potential to increase the diversity of students and faculty in engineering. Part of Purdue s signature-area philosophy is to hire faculty with joint appointments. For TCE, the university is seeking candidates whose expertise straddles engineering and science, including biology, chemistry, physics, pharmacy, veterinary medicine, and agriculture. We need individuals with expertise in how to engineer new tissues and to utilize understanding of manipulation of cells to develop these tissues, says Wodicka. In order to lead the field, we need to attract a cadre of scientists with expertise in this emerging area. The strength of our cluster-hiring approach is that we will bring in faculty members to whatever departments and at whatever academic level is optimum. This approach gives us tremendous liberty to look for the best and attract the best people to Purdue in this realm of investigation. Eight Signature Areas Infinite Possibilities 25

6 Purdue s history of success more than 50 biomedical engineering patents to date has attracted impressive industrial support in the past. Our track record of discovery and translational research is significant and growing, Wodicka says. We hope to leverage our recent successes and existing strengths to fully tap into funding and opportunities with our industrial partners and beyond. Many biomedical engineering companies have research divisions, while others are part of a group dedicated to research and product development. Still, Kokini says, the rise of tissue and cellular engineering may force the industry to reevaluate its approach. The bottom line is that TCE may benefit not only patients with previously incurable diseases or untreatable conditions, but also the businesses and industries trying to help them. Biosensor Solutions: Jenna Rickus, an assistant professor of agricultural and biological engineering and biomedical engineering, works on stabilizing membrane proteins for biosensors that can be used used to detect small molecules in biological samples and environments. A lot of companies may move into new realms, Wodicka says. They can think about not only replacing your fractured or arthritic hip, but also dealing with any other soft-tissue injury once they start expanding their product base by developing replacement tissues for other types of repairs. To help those with AMD, Ivanisevic is constructing templates composed of nanoscopically-defined, lithographicallygenerated regions of vasoactive intestinal peptide (VIP) for use as a transplant scaffold. Her research goals include: delivering VIP and related peptides on retina tissue surfaces using scanning probe lithography to generate templates for tissue regeneration; manipulating and testing the templates to address their mechanical, morphological and chemical properties; and testing the transplant feasibility of the templates. Our research can be used to design new transplant strategies to enhance and speed the regeneration of retinal epithelial cells and reduce detrimental interactions with external conditions, Ivanisevic says. This could result in treatments for a significant segment of the population suffering from blindness. 26 Purdue s Engineering Edge

New to Purdue: The Biomedical Engineering Undergraduate Program What Purdue is seeking for one of its signature areas, it will shortly be cultivating in its own backyard.

7 New to Purdue: The Biomedical Engineering Undergraduate Program What Purdue is seeking for one of its signature areas, it will shortly be cultivating in its own backyard. The university s Tissue and Cellular Engineering (TCE) signature area will attract the top researchers in life sciences and engineering from wherever they may be found. But soon Purdue will be educating future experts in its classrooms and laboratories thanks to a new undergraduate biomedical engineering program just now opening the door to its first class of students. In fall 2004, Freshmen Engineering students will be able to matriculate into biomedical engineering as a professional school the same way they now move into traditional schools such as chemical or civil engineering. We hope to bring in 75 students per year into the program as quickly as possible, says George Wodicka, the head of biomedical engineering and a professor of electrical and computer engineering. Counting sophomores, juniors, and seniors, we ll eventually have 225 students in the program. According to Wodicka, the undergraduate program emerged naturally and by necessity from the graduate program over the past five years. Within a year of starting the graduate program in 1996, George Wodicka we realized the need to create an academic department to support it because the level of faculty and student interest and the growing need of the medical device and the emerging biotech industries were so high. We needed to support the graduate program with a stand-alone and fully functional academic unit. The evolving needs of industrial partners have helped shape the undergraduate program. Many students from the Purdue Schools of Engineering mechanical, chemical, electrical and computer work in the medical device industry, Wodicka explains. We have been routing students into that industry for a long time. But those industries made it clear that they need biomedical engineers in larger numbers as well, because new problems that need to be addressed are becoming more biological in nature. To illustrate, Wodicka points out that although orthopedic implants have typically been synthetic, some companies now have ortho-biologics divisions developing implants with biological origins. This shift in emphasis has created a need for engineers that can bring to Eight Signature Areas Infinite Possibilities 27

New at Purdue: The Biomedical Engineering Undergraduate Program continued bear analysis, design, and computational skills but in the context of biology understanding how these biological replacement

The biomedical engineering undergraduates will be receiving hands-on classroom and laboratory education that bridges those fields.

8 New at Purdue: The Biomedical Engineering Undergraduate Program continued bear analysis, design, and computational skills but in the context of biology understanding how these biological replacement parts are going to function. A centerpiece of Purdue s TCE initiative is the pursuit of researchers with expertise in the life sciences and engineering. The biomedical engineering undergraduates will be receiving hands-on classroom and laboratory education that bridges those fields. However, developing the undergraduate curriculum has proved a daunting task. Life Sciences Mall: The forthcoming biomedical building is being viewed as an academic gateway to Discovery Park. It will be located south of the Herrick Laboratories in what will eventually become a life sciences mall area. There will be much shared between biomedical engineers and researchers in the Bindley Bioscience (left) and Birck Nanotechnology Centers. Biomedical Home: Scheduled for completion in the spring of 2006, the new Biomedical Engineering Building will be a top-of-the-line facility for teaching, research, and engagement. 28 Purdue s Engineering Edge

9 Both biology and engineering are broad and growing very quickly, says Wodicka. The knowledge base is vast. There are a lot of efficiency challenges to integrating into a single curriculum all of the engineering analysis, design, problem-solving, teamwork, and communication skills in the context of important biological principles and the biomedical problems these engineers will be expected to address. Biomedical curriculum designers are working with faculty from departments and schools across campus from biochemistry, biology, and chemistry to electrical and computer engineering and mechanical engineering, for example to develop new courses that integrate engineering skills in the context of teaching biology. At the same time, the curriculum will utilize existing courses. A special feature of the curriculum will be regular lab courses that will enable students to experience in a hands-on manner how engineering and biology overlap. Each semester students will have a biomedical engineering laboratory experience a one-credit course that builds on the principles taught in the other courses and integrates that material, Wodicka says. For example, students learning mechanics will start to see biological applications of that material before they move on to subsequent biomechanics courses. During the last two years of the program, students will be able to focus on a particular biomedical engineering area, such as biomaterials or bioelectrics. That will give them opportunities to work with researchers already working in the TCE signature area. As our graduate program grows and the number of faculty grows we can increase the elective options for the undergraduates, just as the other engineering schools do, says Wodicka. When they complete their four-year programs, where will the graduates go? About half the students will go into the medical device and the biotech industries, and the other half will go on to graduate school or medical school, Wodicka estimates. The field itself at the graduate level is growing rapidly. Students are seeking graduate degrees, and companies are recruiting students with advanced degrees. Thus, a fair number of students will go on to grad school. And from there, some will no doubt become the kinds of research experts Purdue is now looking for to lead and strengthen its tissue and cellular engineering thrust. Eight Signature Areas Infinite Possibilities 29

A New Cellular and Molecular Engineering Curriculum at Rice University

Session A New Cellular and Molecular Engineering Curriculum at Rice University Ka-Yiu San, Larry V. McIntire, Ann Saterbak Department of Bioengineering, Rice University Houston, Texas 77005 Abstract The