Dr. Gail K. Naughton: Advances in Tissue Engineering
By Lilly Manske, MedTech1 Staff
Gail K. Naughton, Ph.D., President and Chief Operating Officer of Advanced Tissue Sciences has been awarded the 27th annual National Inventor of the Year by the Intellectual Property Owners Association (IPO) in honor of her pioneering work in the field of tissue engineering.
As the first individual woman to earn this award, Dr. Naughton is being honored for the process she invented to produce human tissues and organs outside of the human body. Her invention utilizes stromal cells, which are the cells that form the surrounding matrix of a tissue. These cells are seeded onto three-dimensional scaffolding and placed into specially designed bioreactors to simulate the body. There, the cells multiply in layers, secreting proteins and numerous cellular factors, ultimately forming a tissue matrix. Tissue-specific cells are then seeded onto the matrix to form a living tissue equivalent that can be used to repair or replace a patient's own damaged tissue. Her company, Advanced Tissue Sciences, entered into a joint venture with Smith and Nephew to apply tissue engineering technology to create products to treat wounds, such as burns and diabetic foot uclers. Dr. Naughton’s pioneering work in tissue engineering has helped define a new industry dedicated to helping the millions of people who suffer tissue loss or end-stage organ failure.
MedTech1: What is your focus in the area of tissue engineering?
Dr. Naughton: The company’s original focus was on structural tissues. We started with skin, and the first product being TransCyte™, a temporary skin replacement that addresses severe and partial thickness burns. The FDA (U.S. Food and Drug Administration) approved this product, and we are now heading forward with Dermagraft™ permanent dermal replacement skin product, for which the pre-market approval application to the FDA is currently under review. If approved, this product will treat severe wounds such as diabetic skin ulcers, which affect many, many patients with diabetes and can often lead to surgical revisions and amputations.
MedTech1: What was the inspiration for your invention?
Dr. Naughton: While studying different types of tumors and how they can react to vaccines, it became evident that cells grown on a flat dish acted very differently than three-dimensional cells (as they grow in the body). Our invention simply mimics what nature does by giving the cells a three-dimensional framework on which to grow. That became the crux of this entire invention, which has led to therapeutic products in not only skin, but in cartilage and cardiovascular treatments as well.
MedTech1: What is the biggest challenge when you are trying to replicate nature or trying to create a process that imitates nature?
Dr. Naughton: You really have to understand not only the mechanical forces that the tissue or organ is seeing during the development, but all the chemical signaling that takes place between the cells, and between the cells and the proteins that they secrete. It is a matter of working in parallel with outside research as we learn more about new growth factors and cells’ conditions. We adapt those to our systems, so our approach of growing the tissues is unique in that we not only put human cells on scaffolds so that it is a completely human tissue, but we have these proprietary bioreactors that closely mimic the conditions of the body. For example, we grow heart valves by opening and closing the growing heart valve during the manufacturing period, so that the cells actually see the mechanical forces they would unless inside the heart. This forms a more physiological, or more normally functional, tissue that not only looks like a heart valve, but is mechanically as strong as a native heart valve.
MedTech1: How will tissue engineering benefit the public?
Dr. Naughton: I hope that Advanced Tissue Sciences will redefine how transplantation is done. So that in the not-too-distant-future, no patients will have to die because they are on a transplant list and there are not enough organs to go around.
MedTech1: What kinds of tissues have you re-created to date?
Dr. Naughton: In addition to the skin products, cartilage, bone, blood vessels, and heart valves, we have been successful in animal studies for liver implant, for pancreatic islet transplants to be able to eventually cure diabetes, and with other structures such as the partial intestinal replacements, trachea replacements, and replacements of cranial facial bone and cartilage.
MedTech1: How do you think this invention benefits the scientific community?
Dr. Naughton: There are two points here. The whole field of tissue engineering is unique in a couple of ways. First, it forces the integration of a number of scientific disciplines that in the past did not work together. There are cell biologists who need to say what growth factors the cells are making, and what they need to make. There are biochemists that need to work closely to look at the different types of matrix proteins and collagen that the cells are laying down and how they influence the cells’ growth. The transplant surgeons are not only looking for an improvement over what they currently can do, they need to make sure that the patient will not reject the products. Biomedical engineers look at how to test the strength of the tissue and how to better improve the bioreactors to mimic the conditions of the body. Finally, you have polymer chemists. These three-dimensional scaffolds need to mimic the three dimensionality of the tissue or organ that we are trying to grow, and they need to be controlled so that they dissolve as the cells themselves are laying down a tissue. There is a diverse group of scientists working closely together for the first time.
The second point is one of those rare occasions where the science and product development did not go along the normal path of first being discovered in the university, then being funded by the government or seeking seed capital to take the product through pre-clinical studies. The invention was the first in the whole field of tissue engineering. It was born through others in the field as well in the mid 1980s; there was no grant support by the government for this field because the field was so new. Those in tissue engineering jumped straight from concept into public companies. What is so terrific is that the NIH and the others are giving significant grants to us and to other companies in the field. So we are working almost a little backward in this stage where we are starting collaborations with a number of key universities using federal funds to take the next level of products forward.
MedTech1: What does this mean for a person today who is in need of tissue transplantation?
Dr. Naughton: What this means for a burn victim today is that instead of having to go through painful, painful dressing changes three times a day-that require morphine and a hospital stay of a couple of weeks-they can get a tissue engineered product. In our case, it is called Trancytes. It not only helps reduce the pain immediately, but it also allows hospital discharge in a day or two, and much more rapid healing. It is affecting many, many patients today with burns, particularly children. There is long-term trauma involved with the tremendous pain that burn patients have to endure while in the hospital.
For patients with severe wounds such as diabetic foot ulcers, it means having the likelihood of having your ulcer heal and moving away from needing a partial or full amputation. In the near future, patients with joint degeneration and with coronary artery disease should be able to have tissue-engineered products not only replace their own tissue, but in the case of coronary disease, help their own body to regenerate new blood vessels in their damaged heart. This way, they can go forward without having the pain and the debilitating changes in their conditions that occur when they do not have enough oxygen delivered to their heart muscles.
MedTech1: Does the development of your invention depend on the funding you receive?
Dr. Naughton: We have funding from the outside-from the public market-but we also have a number of key government grants that are helping us take our longer-term products forward. For example, we just received a $2 million grant from NIST (National Institute of Standards and Technology) to further develop a tissue-engineered product that induces new blood-vessel formation in the heart. We share a $10-million NIH grant with University of Washington to actually grow pieces of heart muscle for heart transplantation. We also received an $800,000 NIH award to grow replacement cartilage discs for patients with TMJ disease, which affects the jaw. The company received all of these grants this year.
That is just a small list of some of the outside funding. Plus, it helps us to develop the science and collaborate with outside universities in doing so. Endorsement by the government for our approach to tissue engineering reinforces the tremendous potential this technology has to impact healthcare and provide tissue-engineered products to the patients who need them.
MedTech1: How long have you been working on this invention?
Dr. Naughton: It started in 1986. The company raised funding and then went public in 1988. When we started in 1986, the goal was to grow bone marrow outside the body. However, very quickly we saw that this technology had applications to other tissues and organs, such as skin, cartilage and cardiovascular tissue.
MedTech1: What is your personal hope with this invention and where do think it will take you in your studies?
Dr. Naughton: My sincere hope, what fuels me everyday, is being able to make sure that not one patient ever dies waiting for a transplant. Even more importantly, my hope is that patients get their transplants earlier before they become so ill that their quality of life suffers. So just to be able to improve the quality of life for patients with damaged tissue and organs and make sure that everyone who needs products such as these gets them. It is very easy to be inspired and difficult not to be. All you need is a couple of parents to come to you and say “Thank you so much for helping my child,” or have a few little two-year olds run into your arms and give you a hug. That really does it for me.