An Overview of University of Washington Engineered Biomaterials (UWEB)

Buddy D. Ratner, Ph.D., Director
Cecelia Giachelli, Ph.D., Deputy Director

• A small diameter vascular graft used to repair a leg artery occludes with clot necessitating limb amputation.
• A tissue heart valve, after 10 years of good service, begins to mineralize and fail.
• A coronary artery stent induces a thickening of the walls of this tiny artery.
• A hip joint prosthesis, after 12 years allows a patient 12 years of good mobility, but it then begins to loosen.

These examples illustrate some problems we have with implanted medical devices. On the positive side, medical devices are implanted into millions of people each year and largely, lives are saved or the quality of life is improved.

University of Washington Engineered Biomaterials (UWEB) is a National Science Foundation Engineering Research Center. UWEB focuses on today's medical implants. These implants are responsible for a substantial part of a $100B+ medical device industry. UWEB endeavors to improve the performance and safety of current biomaterials used in medical devices.

UWEB is comprised about 25 professors, 100 students, 20 technical staff and 20 companies who are members of the UWEB consortium. UWEB researchers are divided into three thrusts: materials and surfaces, basic biology and clinical and healing sciences. The basic biology discoveries on healing and inflammation from thrust two are translated into materials concepts in thrust one and then delivered for in vivo testing in thrust three.

There are some ideas that are central to UWEB:

• exploit (engineer with) the macrophage and other cells involved in healing
• inhibit non-specific "surface fouling" - encourage specific reactions
• biomaterials should deliver specific biological signals with high signal to noise
• discover the biological processes to turn on, and off key processes in healing
• we aim to create "biomaterials that heal"
• sophisticated surface modification can enhance today's medical devices
• manufacturable strategies are essential Ð we must work with the industry for success
• students must be trained for the real world
• a diverse student population and workforce provides a richness of ideas

The central concept driving UWEB research and engineering is illustrated in this simple diagram:

Today, the body walls off implanted materials as foreign bodies Ð in the future we ask if it is not possible to get materials to cleanly integrate with the body using the process called normal wound healing.

Since the 1996 launch of UWEB, new developments have expanded the horizons of biomaterials. In particular, matricellular proteins have revealed clues about healing, tissue engineering has opened possibilities for combining living cells and materials, knock-out animals have provided a new way to explore biological pathways in vivo, adult stem cells have extended what we might accomplish and gene delivery, anti-sense technology and siRNA methods may allow direct control of cells involved in healing. The principles central to UWEB (inflammation, biomolecules at surfaces, advances in modern biology) are consistent with new biomaterials ideas for advancing the performance of today's biomaterials.

Technical Advances

A large number of specific technical advances have occurred that contribute to our economically and societally important goal of "biomaterials that heal." An abbreviated listing of advances includes novel biorecognition surfaces by templating, an ultrasound drug delivery system, a new class of low cost, biocompatible hydrogels based on amino acids, rational immobilization of key biomolecules to make them more effective at delivering signals, microfiber meshes that heal with no fibrous capsule, new insights into the mechanism of wound healing, desirable properties of hyaluronic acid coatings for controlling inflammation, templated porous gels for angiogeneis and advances in the biology that may lead to a cell-produced elastin vascular graft. Each of these developments has the potential to impact the advancement of fundamental knowledge and the clinical practice of medicine. These developments are hallmarked by creative ideas and outstanding researchers who are receiving worldwide recognition for their efforts.

Broader Impacts

UWEB uses the platform of medical devices and biomaterials to accomplish two goals. One, of course, is helping people by leading to improved medical devices. The second capitalizes on the intrinsic interest that young people have in medicine, anatomy and futuristic topics like bionics. UWEB is now directly interfacing with students in middle schools, high schools and community colleges. Other programs focus on undergrads and middle school science teachers. Our development of CD-ROM based educational games may reach millions of students. To bring enhanced diversity into the UWEB student group, we are "priming the pipeline" by bringing into our classrooms groups of students from the African American Academy of Seattle (our SET-UP program), focusing special attention on making them feel good about science, building their confidence in their abilities to do science and staying in contact with them as they work their way through high school and hopefully into undergraduate programs.

The Future of UWEB

Today, UWEB is learning the secrets of the biology of inflammation and wound healing and applying these ideas to biomaterials. We are moving rapidly to bring these ideas to medical devices and to commercial application. Year 11 of NSF support (2007) will be our last year as an Engineering Research Center. However, the goal is to continue and grow the UWEB concept via funding from the State, the Federal Government and Industry. The areas of exploration that UWEB will focus on include:

Device centered infection
Glucose sensor performance
Healing in soft tissues
Contact lens
Corneal implants
Blood compatibility
Vascular prosthesis
Heart valve
Cardiovascular stent
Long-term (in vivo) non-fouling
Tissue engineering and tissue regeneration scaffolds
Neural and stimulatory electrodes
Retinal prosthesis
Gene delivery
Ultrasound applications
Gene, protein and cell chips
Craniofacial reconstruction
Shoulder and orthopedic joint reconstructions
Dental implants
Biosensors for pathogens
Education/Outreach/Diversity