Welding Wounds

Ask anyone who knows about R. Rox Anderson’s experiments with lasers and chances are you’re going to hear the words “Star” and “Trek” in close proximity. Then again, lower-tech analogies, such as shipyards or auto-body shops, could also spring to mind. But this is not science fiction, and it’s most definitely not conventional metalworking. Anderson works in the world of biology, and his aim is to weld wounds shut.

Wound welding is a high-tech dream that could become a clinical reality soon-if it finds the right niche. Anderson, a Harvard University dermatologist who heads a laser research lab at Massachusetts General Hospital (MGH), thinks lasers could supplant the relatively primitive sutures and staples now in widespread use. “We should not be putting people back together or doing surgery and moving organs around, tacking them in there with little bits of string and chunks of metal,” he says. “It’s archaic.”

Anderson and his research colleagues aren’t the only ones intrigued by the potential of welding the body’s cut and injured tissues back together. A handful of biomedical startups and established laser manufacturers are working feverishly on it, and larger surgical companies are keeping a close watch on the progress. The work is driven by the potential advantages of laser welding: faster surgeries, fewer complications, quicker healing. The hard commercial reality, however, is that, for most common procedures, suturing and stapling are cheap and deeply entrenched. But recent advances in surgery, especially ones in the fast-growing field of minimally invasive procedures, are creating opportunities that could make laser welding a clinical reality.

Thus far, the rush to practical applications has outpaced the scientific understanding of what happens at a bio-weld site. What is known is that when the laser heats the edges of a rent, proteins there begin to denature or “melt.” As the material cools, it solidifies and-if all goes according to plan-the edges coalesce, leaving a seam like a weld in a metal pipe. To aid this melding process, researchers often add a protein-based solder into the wound in order to reinforce the seam.

The method is attractive to surgeons because, for one thing, it might ultimately become more highly standardized than suturing, which is still more art than science. “How far away they put the needle from the edge of the tissue, how far they put one stitch from another, how tightly they tie the knot or pull the stitch between knots-all of those are subjective and every surgeon will do them differently,” explains Dix Poppas, director of pediatric urology, reconstructive and laparoscopic surgery at New York Hospital-Cornell University Medical Center and a tissue welding researcher. And while mechanical staplers take some of the craft out of joining tissues, they aren’t always practical for delicate, irregular or very small structures.

Unlike sutures or staples, welding wounds also offers a watertight seal to hold bodily fluids in, preventing blood loss, infections and repeat surgeries. And lasers don’t leave behind bits of string and pieces of metal that can inhibit healing and cause inflammation, scarring and constriction of newly repaired vessels.

The first attempts at laser tissue welding date back almost 20 years. Over that time, lasers have emerged as an invaluable tool for surgeons for cutting or destroying tissue and have, for instance, revolutionized the removal of cataracts. But with the exception of a widely used laser procedure for reattaching a retina, welding has yet to prove itself the method of choice for tissue closure.

These days, however, many biomedical researchers feel that the field is reaching critical mass. Encouraging results from lab and animal studies continue to pile up, and preliminary human studies have shown welding’s potential utility in surgeries such as vasectomy reversal, artery and vein reattachment and the correction of penile birth defects. “I’ve been doing this for 16 years and it used to be that no one even listened-now I get calls every week,” says Poppas.

Despite the enthusiasm, it remains uncertain whether tissue welding can sew up a spot in the hotly competitive surgical business. For it to become a standard medical technique, doctors will need access to safe and reliable off-the-shelf welding devices and “solders.” Some of these items are now in human clinical trials, but they still must prove themselves and gain regulatory approval from the Food and Drug Administration. And the companies developing the products will need to define and capture a market for their technology that will provide lucrative returns.

Taking the Art Out

A crucial step in making tissue welding widely applicable is building easy-to-use laser systems that are safe and reliable in many surgeons’ hands, not just in those of the highly skilled researchers who are developing the systems. Though Poppas and other surgeons have earned reputations as excellent welders, their technique is still in some ways an art form. Judging when to turn the laser off, for one thing, is tricky; if the tissue gets too hot it will burn, if it doesn’t get hot enough the weld will be weak.

Poppas, who uses protein solders when he welds, explains that eyeballing the endpoint of a weld leaves a lot of room for error. “The only way to do it is by looking at visual changes that occur in the solder-when you see it harden, when you see it glisten over, when you see it bubble, when you see it turn opaque. Those are extremely subjective parameters, and every surgeon is going to have a different opinion on what a weld looks like.”

To make the process consistently reproducible for the average surgeon, Poppas is working with Danvers, Mass.-based Abiomed to test a “smarter” welding system. The Abiomed approach employs an infrared detector, similar to those used in ear thermometers, to measure the temperature of a spot as the laser heats it. The signal from the thermometer feeds into a microprocessor, which adjusts the laser’s output to maintain the temperature within a few degrees. The system, according to Robert Stewart, a principal staff scientist at Abiomed, “takes the art out” of welding. “Anybody can set a temperature and weld and it will work.”

In some of the delicate operations targeted by tissue welders-for example those involving newborns and even fetuses prior to birth-such reliability could be a matter of life and death. While these high-risk applications give laser tissue welding a chance to shine (sutures would tear through fragile fetal tissues), they also highlight the stakes involved in keeping the laser in check. To perform the operations safely, researchers from Lawrence Livermore National Laboratory in Berkeley, Calif., have invented a feedback-controlled welding system, and, working with Conversion Energy Enterprises of Spring Valley, N.Y., the team is testing the feasibility of using it to seal and join together newborn and fetal blood vessels.

Dead On

Although a reliable, easy-to-use laser system is essential, many researchers believe simply using a laser to melt the proteins found at the site of the wound can’t make a seal strong enough for clinical use. So, like plumbers and electricians, surgeons have turned to “solders”-in this case, proteins derived from animal or human tissues that melt into the wound and bolster tissue bonding.

While still a medical student in the mid-1980s, Poppas spent several frustrating months in the lab operating on rat urethras, using a laser alone to seal them. “I kept seeing a potential there,” he recalls, “but something wasn’t right.” The laser wasn’t reliably producing a bond strong enough to compete with sutures. So Poppas started playing with protein-rich strips of muscle or vein, or drops of blood that he laid over the cut vessel before hitting it with the laser light. The results were better but still not good enough. He then tried pure protein-a compound called albumin that is abundant in blood serum and egg whites. “I mixed it up and put it on the wound and bonded this thing and it was unbelievable, the results were just phenomenal,” he says. “In fact, I was supposed to go to a [Grateful] Dead concert that day and I missed it because I kept doing these experiments.”

Ticking Clock

With solder science solidifying and the laser technology tuning up, proponents of tissue welding are upbeat. MGH’s Anderson, for one, believes he and his colleagues are heading toward a reality where eventually “there would be an off-the-shelf, user-friendly system for tissue repair that looks a lot like what they do on Star Trek.” But before technology and science fiction can meld, tissue welding faces a daunting challenge; it still must find an initial application to get the technology on the shelf and open up the market.

And the clock is ticking. Some proponents worry that if welding doesn’t become commercially viable within the next few years, potential niches will be filled by a new generation of biological and synthetic tissue glues. Surgical adhesives and sealants-some synthetic-based cousins of Superglue and others made of biological materials-promise many of the same benefits as tissue welding. While no adhesive meets all the criteria for an ideal tissue sealant, glues are beginning to gain regulatory approval for limited applications such as the closure of small skin wounds or incisions. And adhesive developers are already working on stronger and more biocompatible products.