Human body as skin-growing factory?

It happens quickly, say surgeons. You step off a curb or light a backyard grill, and your life is changed forever by profound injury. Patients arrive at major trauma centers every day with burns covering most of their bodies, or with a combination of skin, bone and muscle lost to terrible circumstance. Trauma surgeons do what they can to put things back together but are limited by today's tools.

In recent decades, surgeons have partnered with bioengineers to try to create better technologies for the replacement of lost tissue. They still have a ways to go, but surgeons may one day take a product "out of a box" and use it to patch large gaps of missing tissue.

Along these lines, research efforts captured in a recent Wired Article seek to create truly artificial replacement skin out of self-healing polymers and flexible electronics. Another near-future approach will be to use a patient's own body as a high-speed skin-producing factory with the help of appliances, engineered proteins and biochemicals.

We asked Steven Thomas, M.D., a UAB specialist in reconstructive surgery for patients with complex wounds and severe burns, for his take on both approaches. As an assistant professor in the Department of Surgery within the UAB School of Medicine and a former army surgeon, Dr. Thomas has spent much of his career looking for a better way to repair damaged tissue, layer by layer.


Show notes for the podcast:

00:56 UAB has the biggest burn and trauma centers in Alabama and Mississippi, and Dr. Thomas' team deals regularly with patients that have lost large amounts of skin, muscle and bone.

2:21 Burns pose a particular challenge when it comes to repairing skin, especially when all layers of skin (dermis, epidermis, etc.) have been destroyed. This requires surgeons to borrow skin from the non-burned areas. They can then use bioengineering techniques to regrow skin, but currently technologies do so slowly. When burns cover the majority of the patient's body, it is a challenge to regrow enough skin fast enough to avoid scarring.

3:22  According to Dr. Thomas, there is no current treatment option that efficiently and quickly makes available large amounts of replacement skin. Those that are available cost hundreds of thousands of dollars, require multiple procedures and don't work for all patients.

3:45 One product on the market now called the cultured epidermal autograph is grown from a patient's own skin cells by the biotech company Genzyme. From 2 postage stamp-sized biopsies, the company says it can  grow enough skin to cover a patient’s entire body, but it may cost $600,000, said Dr. Thomas. What the field needs is inexpensive replacement skin that you could take off a shelf and apply.

5:10  Many current research efforts seek to create good artificial skin, but no one product has gelled yet. Today's attempts are not durable enough, he said, and need to be replaced by something that can be shipped and stored without losing its useful properties.

6:48 Some of the frontiers in artificial skin research include polymers that can knit themselves the way real skin does, but nothing to date does the job as well as the body itself  The problem is large gaps in skin, which scar instead of knit.

7:58 Dr. Thomas is convinced that the future of the field will be in using the patient's own body as a high-speed bioreactor to make replacement skin, but it needs help. A current UAB research project led by graduate student Paul Bonvallet in the lab of Susan Bellis, Ph.D. seeks to provide that help using the protein collagen taken from cows. Collagen is the ingredient that gives shape, strength and structure to the body's connective tissues like bone and tendon, as well as to skin.

8:15 The UAB project is having some success in laying a mat of collagen across large areas where a patient has lost all layers of skin. The mat serves as a framework or scaffold that enables the skin to re-knit in an orderly way over of the dermis. The experimental product contains no cells, but the body populates it as needed.

8:42 UAB is among the first in the country to combine dermis scaffold and skin grafts to get patients re-covered with skin after major injuries. Dr. Thomas mentioned one accident victim that was hit and dragged underneath a garbage truck, loosing much of his skin, along with some bone and muscle, from the waist down. Through a combination of therapies, the surgeons were able to re-grow the lost skin, and the man is up and walking today. Dr. Thomas believes that in most places that man would have lost his legs.

9:21 Underway already at UAB are efforts to combine scaffolds with different mixes of stem cells and enzymes that encourage growth. The combination of framework and tailored cells is getting closer and closer to mimicking native tissue, itself a mix of cells and scaffolds.

10:09 Depending on the type of collagen used, it can act as the highway with guide rails that shows skin cells the pattern they need to grow in to cover over a wound or burn. Some types of collagen are better at doing this without leaving a scar. Dr. Thomas' team has been able to get good-sized wounds to heal in a few weeks using collagen biotechnology that used to take months.

11:57 Returning to the effort to generate truly artificial skin mentioned in the Wired article, Dr, Thomas said that the military has invested in such technologies in hopes of better regenerating skin for wounded soldiers. Institutions like DARPA, the Defense Advanced Research Projects Agency, and AFIRM, the Armed Forces Institute of Regenerative Medicine, fund related research projects.

12:15 Dr. Thomas thinks that, while the body may be best at creating skin for burns and wounds, artificial skin made from polymers has the potential to dramatically improve the nature of artificial limbs. During his years at the Brooke Army Medical Center burn unit, Dr. Thomas saw lots of amputees come in, and worked with many soldiers trying to get used to prosthetic limbs. He said today's prosthetic arms have no proprioception, the sense of where the limb is in space and with respect to the rest of the body. They also have no sense of touch. Creating limbs with these capabilities would represent a huge leap for people with prosthetics, he said.

14:00 Dr. Thomas has worked with the Bellis lab experimenting with electrospinning, a process that uses electrical charge to draw a nano-scale thread of material from a liquid. It is particularly suited for the production of fibers out of large and complex molecules like collagen.  Electrospun collage can be woven into mats that promote cell growth and the penetration of cells into the engineered scaffold.  The other great thing about electrospun materials is that they are inexpensive.

15:59 To fill in a complex wound, Dr. Thomas would like to have a treatment that could regrow skin, muscle and bone in layers. Stem cells engineered in concert and in layers to achieve such complex healing is a future possibility, he said. It may be too much to ask one product to achieve all that, and may require a combination of stem cell-driven products used together with precise timing.

Jolie news highlights changing nature of mastectomy

Breast cancer cells

The world pays extra attention to diseases when celebrities have them, so it dominated the news this week when actress Angelina Jolie revealed that she recently had a double mastectomy. Tests had revealed she has the BRCA1 genetic variation known to drastically increase breast cancer risk. A sad detail in her case was her mother's death from the disease, which points to the interplay between genetic tests and family history when assessing risk.

The media did a good job of explaining that each case is different, and that women should make decisions with respect to breast cancer surgery in partnership with their doctors and genetic counselors. Included in the coverage was a fine piece by The Associated Press that described how women who make the same decision as Ms. Jolie now benefit from new approaches and technologies.

The nature of mastectomies has changed in recent years to save more of the breast, reduce scarring and pain and, in some cases, to enable breast reconstruction during the same surgery that removes the cancer. About 220,000 women are diagnosed with breast cancer each year in the United States, and 40,000 die.

We asked Helen Krontiras, M.D., co-director of UAB Breast Health Center and scientist at the UAB Comprehensive Cancer Center, for her take on the news and emerging trends in breast cancer surgery, which is her specialty.

Making it easier

Women who had double mastectomies in years past likely faced the removal of their entire breasts, including nipples and good deal of skin. They then faced a series of surgeries required to rebuild the breast with skin taken from the belly, construct a nipple and tattoo a ring around it.

Today, most women chose to have some degree of reconstruction done during the same surgery as their mastectomy, said Dr. Krontiras. For reconstruction requiring implant, surgeons must still, in many cases, put in expanders to stretch the skin for a time before a second surgery to put the implant in. Some patients go straight to implant at the time of mastectomy. According to the AP article, about 25 to 30 percent of women nationally get immediate reconstruction.

Despite a growing focus on the cosmetic aspects of breast reconstruction, Dr. Krontiras emphasized that the first goal is obviously to remove all the cancer. Second to that, but still important, is the effort to preserve cosmetic outcome. In some patients, she starts with chemotherapy first to try to shrink the tumor to the point that patients become candidates for skin saving techniques. One factor making this possible is the increasing sophistication of chemotherapy against breast cancer based on the realization that breast cancer can be one of several cancers, with treatment now tailored for each patient's genetic make-up.

In addition, new approaches to mastectomy that save original nipples are gaining in popularity. Many studies now show that the rate of local breast cancer recurrence in patients that retain their nipple and areola are low and on par with older procedures that remove them, Dr. Krontiras said. Injections of body fat are used in some cases to fill in defects that may occur as a results of removing breast tissue.

Looking forward, women may one day benefit from an experimental out-patient technique called cryoablation. A liquid-nitrogen-cooled probe freezes bits of cancer to death, with the dead cancer tissue removed by normal bodily processes. The technique is currently being tested in clinical trials.

Talk it over

Jolie made the decision to have the double mastectomy because counseling revealed she had the BRCA1 gene, and because her mother had died of breast cancer. It has been reported that her health team told her she had an 87 percent chance of getting breast cancer.  Of course, such numbers are the opposite of universal, and vary greatly form patient to patient.

Dr. Krontiras recommends that women diagnosed with the BRCA 1 or 2 gene start with a discussion of options with their doctor and genetic counselor. Each patient’s risk for cancer will be managed by varying combinations of surveillance, chemoprevention and prophylactic surgery of breasts and/or the ovary. There is no once-size-fits-all approach.

She added that she hopes the widespread attention generated by Jolie’s announcement does not lead to a whole-sale increase in requests for mastectomy. Genetic predisposition for breast cancer affects less than 10 percent of all women diagnosed with breast cancer.

However, women who do carry such a gene can have an up to 85 percent lifetime risk for breast cancer. Therefore, asking questions about family history are important, and patients need to learn about risk on both their mother’s and father’s sides of the family.

While the BRCA genes are important predictors of breast cancer risk, they are likely to be the first of many as yet undiscovered genetic and familial factors that contribute to risk, Dr. Krontiras said. Even those with negative BRCA tests should be watched closely if family members have developed breast cancer.
     
Women and family members interested in genetic counseling with respect to breast cancer can visit the UAB Cancer Genetics Clinic site. There is a website offered by The National Society of Genetic Counselors that has information about family history, as well as another by the National Cancer Institute on preventive mastectomies.  More commentary is available in this UAB news story and in this article and video from Medpage Today.