Attendees
A. Barrow, W. Baxter, W. Butler, S. Chien, R. Cosan, D. Cuplin, J. Griffin, D. Gough, T. Matusov, M. Mazzoni, J. Penhune, L. Roteliuk, A. Ratcliffe, G. Schmid-Schönbein, I. Tyus

Approval of Minutes from 10/19/01 meeting
Approved as submitted.

Dr. Gough announced Dr. Chien's appointment as a University Professor. He spoke about the title of University Professor, which is awarded to scholars of international distinction who are recognized and respected as teachers of exceptional ability. Though there is no limit for number of University Professors at any one time, the special responsibilities of this title and the rigor of the selection process keep the group very small (22 in the entire UC system). The criteria for appointment are exceptionally high and Dr. Chien definitely meets and exceeds these criteria. Having Prof. Chien hold this appointment while being a faculty member of the Jacobs School of Engineering and of UCSD brings enormous recognition to him and great pride to the school. A party to celebrate this great event will be scheduled for Thursday March 28. The celebration will be held at the UCSD Faculty Club. The invitations to the party will be sent to the Board members.

Dr. Penhune mentioned that this appointment would foster the MRU project. He expressed his assuredness that Dr. Chien's leadership would make the MRU a functioning body and not just a project on paper. Dr. Chien reported on the recent developments in the work on the MRU project. All nine UC campuses have joined the proposal.

Cardiovascular and Orthopaedic Tissue Engineering at Advanced Tissue Sciences
Tony Ratcliffe gave a presentation about the company research and technologies.

Advanced Tissue Sciences' technology uses living human cells and scaffolds to create a three-dimensional tissue. This technology can be applied to all human cell types and, with more than 200 different cell types in the body, provides multiple opportunities for new products.

Advanced Tissue Sciences (ATS) uses the cell-scaffold approach in producing engineered tissue. In this approach bioengineering, cell biology, biochemistry, polymer science, and transplantation are used to grow human living organs and tissues.

Tissue engineering is used for tissue repair and replacement. Extracellular matrices (ECM) facilitate repair, ECM plus cells induce repair, and ECM plus cells plus scaffolds replace the damaged tissue. In the cell-scaffold technology the cells put on biocompatible scaffold multiply on the scaffold and secrete growth factors and human matrix proteins. As a result, we have a completely human form of tissue.

Scaffold variables include degradation rate, mechanical properties, polymer composition, porosity and pore size, shape, size, and microarchitecture. One potential benefit of cell-scaffold tissue engineering is that cells deposit a natural ECM and secrete growth factors (such as VEGF). The ECM and growth factors provide integrin binding sites and chemotaxins to encourage host cell integration. Tissue-engineered vascular graft (TEVG) may be more responsive to physiological signals and enhance remodeling. There are various scaffolds available for tissue engineering such as: felts, braids, and sponges.

Cells are required to proliferate, demonstrate the required phenotype, respond to culture conditions (growth factors, mechanical stress), and deposit extracellular matrix. Various bioreactors are used for tissue engineering products such as TransCyte, Dermagraft® (DGF), NeoCyte, and TEVG.

The TransCyte product is made in an automated, multiple-unit production system that maintains a closed system for product asepsis from assembly and sterilization to end use.

The clinical results of the product are impressive, particularly in the treatment of second degree burns on children.

Dermagraft®, which is a living, bioengineered, human dermal replacement, is approved for use in the U.S. to treat diabetic ulcers (800,000 patients/yr in the US - target market is 300,000 - 400,000 patients).

Additional clinical trials are underway to investigate its use to treat venous ulcers (700,000 patients/yr in the US) and pressure sores (over 1,500,000 patients/yr in the US).

Dermagraft is capable of producing and releasing a variety of growth factors and cytokines. A number of these have been identified as angiogenic agents. Specifically, VEGF, TGF beta family, and Angiopoietin-1 (Ang-1). Furthermore, recent angiogenic studies have demonstrated the co-expression of Ang-1 and VEGF to result in the formation of a mature and non-leaky microvasculature. Dermagraft produces substantial quantities of angiogenic factors.

Vascular grafts have the potential to fill cardiovascular and vascular clinical needs. The ATS has developed two types of vascular grafts: coronary grafts (over 600,000 coronary artery procedures/yr), and peripheral grafts (115,000 peripheral vessel graft procedures/yr).

Epicardial Patch for Angiogenesis in Infarcts
The ATS researchers have a hypothesis that an epicardial patch constructed of Dermagraft will stimulate an angiogenic response within an area of cardiac tissue subjected to infarct damage.

Studies on the mice provided evidence in support of this hypothesis. Using the thermal occlusion of a coronary artery, at the time of acute infarct, a patch of either non-viable or viable Dermagraft contruct is sutured over the damaged cardiac tissue. The hearts of the mice with such myocardial infarcts and treated with viable Dermagraft had appearance close to that of normal hearts. The survival data of normal animals and infracted animals with viable Dermargaft treatment were 100%. In contrast, in the infarct-only (untreated) group, only approximately half of the mice survived.

Blood Vessel Substitutes
Currently, the available sources are mainly autologous vessels such as internal mammary artery or saphenous veins and Synthetic vascular grafts such as dacaron, ePTFE, but there are some limitation associated with each of these grafts. These limitations include limited availability of patients' vessels, which often have pre-existing pathologies, and the high cost and morbidity associated with harvesting.

Synthetic grafts have been developed over many years. Despite many successes, these grafts are faced with some challenges including thrombosis, pathological remodeling which result in decrease in patency of these grafts, adverse immune response, and aneurysm and rupture of the grafts.

Tissue engineered vascular grafts were formed by making tubular scaffolds, seeding smooth muscle cells on these scaffolds, culturing them and finally seeding endothelial cells on the luminal surface.

The ATS scientists have used fluid flow to orientate the smooth muscle cells circumferentially, and the endothelial cells longitudinally, similar to their orientation in native vessels.

Constructs with either cPTFE or braided PTFE were made and implanted into animals. Importantly they were able to remain patent for up to three months.

This approach may one day provide suitable clinical grafts for implantation at peripheral, arteriovenous, or coronary positions.

Dr. Ratcliffe also briefly covered such topics as tissue engineered articular cartilage, tissue engineered cartilage, perfusion - compression bioreactor schematic, long-term mechanical stimulation, surgical procedure, osteochondral defect repair, cartilage-bone construct grown in vitro, cartilage-bone construct implantation, and cartilage-bone construct 4 weeks post implantation.

At the end of his presentation, Dr. Ratcliffe also spoke about ATS collaborators who worked together with the company on many of the projects and research studies. Dr. Shu Chien, Dr. Fung, Dr. Coutts, and Dr. Amiel of UCSD are among them.

After the presentation, the members were discussing problems in FDA-company relationships. Dr. Ratcliffe said that though FDA and Advanced Tissue Sciences have the expedite proposal submission and review process, still it takes too much time to get the study projects approved. Members shared their own experience in dealing with FDA and also praised Advanced Tissue Sciences and Dr. Ratcliffe personally for their role as educators for the FDA. Dr. Ratcliffe told the meeting about the problems they have with the present regulation system. FDA does not have tissue engineering as a separate study field and ATS products fall either under devices or biological products. Both regulations may pose problems in getting their products certified.

At the end of his talk Dr. Ratcliffe spoke about the emerging career opportunities for the UCSD students at Advanced Tissue Sciences.

Dr. Chien introduced and welcomed a new member of the board from Edwards Lifesciences, Luchy Roteliuk, who had replaced Mark Konno. Mr. Konno served the Board extremely well and Dr. Chien expressed his warm welcome to Mr. Roteliuk.

Industrial Internship Program Update
Imani Tyus spoke about the progress of the graduate student industrial internship placement. Nearly all of the students who applied for the program were placed. Imani asked the Board members to help in placing the three students who are still looking for a company to do their internships.

Imani also announced an annual gathering on May 16 where the students and industry representatives can meet in an informal setting to discuss the opportunities and benefits of working in industry.

Jennifer Griffin made an announcement about the annual graduate student symposium, which will take place on March 9.

Board members again spoke about the process of FDA certification. They spoke about the differences of the process in US and Europe. Very often the differences in regulations are drastic and the products go under different categories in US and Europe.

Dr. Penhune suggested a workshop on the transfer of technology and regulation issues for the Board members. All members agreed that such a workshop would be very interesting and allow the members share their experience and ideas about the process.

It was decided that the workshop would be coordinated through the IAB Board.

The Powel-Focht Building Construction Update
Dr. Chien gave an update on the new building construction. The construction is on schedule and Dr. Chien showed some slides of the site to the Board members. The moving into the new building is scheduled for September-October of 2002. The ceremony to celebrate its construction will be held on August 12, 2002.

Other Business and Next Meeting Date
A survey form will be sent to Board members to select the most suitable date for the next Industrial Advisory Board Meeting.

Respectfully submitted: Tatyana Matusov