Sealing the gap

Bonding the edges of human tissue is a vital step in most surgical procedures. In medicine today, surgeons suture or staple incisions, and the tissue bonding process occurs naturally. Laser-assisted bonding, which is in the developmental stages, may help improve post-operative bonding, ultimately speeding the healing process.

Researchers have known for 20 years about the benefits of laser heating, but the field has lacked definitive research on how it works or how to optimize the process.¹ There are two fundamental approaches to laser-assisted bonding of tissue: laser welding (heating the adjacent edges of cuts in tissue by a laser beam) and laser soldering (applying a biological solder onto the adjacent edges and heating the solder and the underlying tissue); both are promising surgical techniques.² They are, in principle, easier to master and faster to perform than standard suturing, and they generate an immediate watertight seal. Because these methods are less invasive, the patient experiences reduced tissue trauma and less reaction to foreign bodies. Welding and soldering lead to faster wound healing and better cosmetic results; both are compatible with endoscopic applications.

To exploit these techniques, we must understand the bonding mechanism and optimal parameters. In early experiments, we carried out pathological examination of tissues that had been heated by a laser beam. We found that heating incisions to temperatures of 40°C or lower causes no effect, while heating incisions to temperatures higher than 70°C may cause thermal damage. To investigate this range and determine the temperature band at which laser bonding works best, we developed a fiber-delivered laser system that allowed us to control tissue heating based on the tissue temperature. With this system, we tried to define the exact conditions for optimal soldering.

For beam delivery, our group developed unique optical fibers made of polycrystalline silver halides (AgCl_xBr_1-x), which are highly transparent in the mid-infrared spectral region (3 to 30 µm). We normally make fibers with diameters 0.5 to 1.0 mm and lengths up to 10 m. These fibers are flexible, nontoxic, and nonsoluble in water, and, unlike the "photographic" silver halides, they do not darken under visible light.³

We used the fibers with a carbon-dioxide (CO₂) laser and an infrared (IR) detector to make a system for monitoring and controlling the temperature of a spot on the tissue surface (see figure 1). The AgClBr fiber carries less than 1 W of 10.6 µm radiation from a CO₂ laser to heat a 2- to 3-mm diameter spot on the surface of the skin to temperatures lower than 100°C. The heated spot emits mid-IR radiation whose intensity is determined by the surface temperature T. A second AgClBr fiber captures this radiation and delivers it to a pyroelectric IR detector, filtered to block reflections from the CO₂ laser. The detector drives a feedback loop that controls the power emitted by the laser, and thus the temperature of the heated spot. The stability of the surface temperature obtained in vivo (in animal models) was usually ± 3°C around the preset temperature.⁴

Figure 1. Fiber-optic CO₂ laser soldering system features temperature control.

We focused on laser soldering, rather than laser welding, and selected albumin as a biological soldering material. Albumin is a water-soluble protein that coagulates when heated. It is highly absorptive at CO₂ laser wavelengths, which allows us to more easily control the temperature of the albumin layer, and thus the bonded tissue. The solder also adds immediate mechanical strength and reduces the overheating of the underlying tissue.⁵

We first investigated the optimal parameters for laser soldering of tissues by bonding incisions in animal subjects. We pulled the edges of the incisions close together and applied a thin layer of albumin. We then used the laser soldering system to heat a spot on the incision to a temperature T, for a time t. Using such spot soldering we closed the whole incision. In a control group we closed the cuts with standard sutures. We obtained the incisions for pathological testing at 3, 7, 14, and 28 days. The skin sections were subjected to either tensile strength measurements, tissue pathology tests, or scanning electron microscopy (SEM) analysis.

The strongest tensile strength was achieved for soldering at 60°C and roughly 8 to 10 s of exposure per spot. When soldering at 60°C and 8 to 10 s, the immediate tensile strength of the laser-soldered incision was lower than the strength of sutured incision. Tests conducted after the procedure, however, showed that the strength of the laser-soldered incision gradually increased, and it became as strong as a sutured incision after three days. We also used SEM and tissue pathology tests to compare the laser-soldered incisions at these parameters to the ones that had been sutured. The results of both methods confirmed that soldering at 60°C and 8 to 10 s gave optimal results. We used these parameters for all our further experiments on other types of tissue.

Suturing or stapling incisions introduces foreign materials that cause inflammation and leave visible scars. In an attempt to determine whether laser soldering causes less damage and scarring in bonded tissues, we tested incision healing on animal subjects using both laser soldering and suturing.

After 10 days, laser-soldered scars looked better cosmetically than sutured ones. Microscopic studies indicated that the wound healed better and faster in soldered scars, compared with sutured scars. Pathological tests studying the inner layers of the skin (dermis and hypodermis) 3, 7, 14, and 28 days after the procedure indicated that the soldered incisions exhibited less inflammation than the sutured ones. Two weeks after the procedure, the inner layers of the soldered incisions looked exactly like normal tissue (without incision). In comparison, even after 28 days, the sutured incisions were still visible.

SEM results indicated that the albumin-assisted CO₂ laser soldering of cuts resulted in an even and smooth surface appearance, hardly distinguishable from that of normal intact skin. Suturing produced scars with surfaces free of debris, but the quality of the sutured incisions was inferior to that of the soldered ones.

When an area of the cornea is damaged, it is often necessary to perform a corneal transplant. A small disk is surgically removed from the cornea. A disk of the same size is removed from the cadaver of a donor and is sutured in place of the removed disk. The sutures may cause inflammation, and it is sometimes necessary to keep the sutures in the eye for more than a year. Laser soldering may offer an alternative way of attaching the disk to the cornea.

We tested the process on animals by soldering one eye and suturing the other. Under the operating microscope, the tissue surrounding the soldered area remained clear with no charring. The anterior chamber, which lies between the cornea and the lens and which contains a transparent fluid--the aqueous humor--also remained clear.

In samples for pathological tests taken 16 hours after bonding, the soldered incisions showed no thermal damage and minimal inflammatory reaction. Coagulated albumin solder bridged the small gaps between the edges of the incision (see figure 2a). New epithelium was starting to form at the cut edges.

Figure 2. Light microscopic photographs at 400 X of the bonded sites on a rabbit cornea taken 16 hours after the procedures. a. laser-soldered tissue; b. sutured tissue.

By comparison, in the sutured area, we found a moderate inflammatory reaction, and the gap between wound edges was larger than in the soldered corneas (see figure 2b). Sutured incisions in both rabbit and pig corneas developed a multitude of new blood vessels around the sutures, which can cause rejection of the corneal transplant and reduces transparency of the cornea.

We also conducted preliminary experiments of laser soldering on incisions in other tissues such as blood vessels, urinary bladders, and ear drums. All exhibited good bonding.

Laser welding and laser soldering have yet to be widely used in the clinical setting. This is probably due to three reasons: The initial tensile strength has been too low during the first few days compared with standard closure methods; there has been a lack of consistency in tests; and some methods result in thermal injury to neighboring tissue.⁶ Few researchers have reported reliable results, and only a handful reported clinical trials of laser welding or soldering have taken place.

Our fiber-optic laser soldering system provides reliable bonding with sufficient tensile strength and minimal thermal damage. Using predetermined parameters, we found that on both skin and corneal incisions, soldered scars look better, get less inflamed, and are stronger than sutured scars. Preliminary results indicated that the same holds for blood vessels, urinary bladder, nerves, and other types of tissue. We expect that the fiber-optic system will make it possible to carry out laser soldering in many medical disciplines, and it may be viable to use this technique endoscopically. oe

Acknowledgments

The authors thank the Israeli Academy of Sciences and the Israeli Ministry of Trade and Industry (IZMEL program) for their support of this project.

References

1. K. K. Jain and W. Gorisch, Surgery 85 (6), pp. 684-688 (1979).

2. L. S. Bass and M. R. Treat, Lasers Surg. Med. 17(4), pp. 315-349 (1995).

3. S. Shalem et al., Fiber and Integrated Optics 16(1), pp. 27-54 (1997).

4. O.Shenfeld et al., Laser Surg Med 14(4) pp. 323-328 (1994).

5. E. Strassmann et al., Proc. SPIE Vol. 4244B, pp. 253-265 (2001).

6. S. Reiss, Biophotonics 8(2), pp. 36-41 (2001).

Abraham Katzir has science in his genes. "My late father, Aharon, was a world-renowned scientist, as is my uncle, Ephraim, who was president of Israel," says Katzir, a professor of physics at Tel Aviv University and a specialist in optoelectronics. "Both believed that scientific methods should be used for the benefit of man." Katzir is following in their footsteps. "My goal in life is to apply the results of scientific research to help people," he says. Katzir's approach to scientific work can be summed up in one word: collaboration.

In 1977 Katzir started the applied physics group at Tel Aviv University, where engineers, physicists, and physicians work side by side to develop medical, environmental, industrial, or agricultural instruments and methodologies using photonics technology. "I usually have about 20 people in my lab; half are students and half are professional researchers," says Katzir.

The laser-welding work discussed above is one product of Katzir's applied-physics laboratory. Examples of other research projects include an IR fiber-optic system for endoscopic laser surgery or therapy, an IR fiber-optic sensor for early detection of cancer, and a fiber-optic probe for in situ measurement of pollutants in water and soil.

About 18 years ago Katzir felt that there was a need to bring together researchers from the biomedical and the engineering-science communities to a conference that focused on medical applications. Katzir contacted Joe Yaver, then the executive director of SPIE, and convinced the board of directors that the organization should coordinate such a meeting.

"At our first conference, we had a small gathering where roughly 20 papers were presented," says Katzir. Far from discouraged, Katzir ran the Symposium for Biomedical Optics for the next 15 years. Today, more than 1000 papers are presented annually.

"To me, this is one of the most rewarding things that I've done in my life," says Katzir, who likes to be called by his Israeli nickname, Katchul. "This work has been good: good for me, good for SPIE, and good for mankind. That's not bad!"