As the scope of transnasal cranial-base surgery expands, reconstruction of the complex residual defects remains a challenge. Laser welding is a novel technology that can be performed endoscopically and offers the potential of producing instantaneous, watertight repairs using a chromophore-doped biologic solder.
The field of endoscopic cranial-base surgery has undergone significant evolution in the past decade, fueled largely by advances in imaging and instrumentation. While the limits of these approaches have yet to be reached, difficulties in reconstructing the resultant defects have become significant obstacles. Successful reconstruction requires a technique that recapitulates the complex morphology of the cranial base while simultaneously withstanding the hydrostatic forces exerted by the cerebrospinal fluid compartment. Current strategies have evolved around the fundamental limitations of access in endoscopic approaches and thus represent a departure from the principles of surgical closure in an open field. In place of meticulous tissue apposition and watertight suture lines, surgeons are limited to multilayer grafting and the liberal application of relatively weak biologic glues, which often obscure the defect, thereby impairing the intraoperative assessment of the closure. These techniques may require prolonged nasal packing and lumbar drain placement to further support the repair in the immediate postoperative period. Despite these limitations, the low-pressure profile of cerebrospinal fluid coupled with the dense vascularity of the dura and mucosa allow for robust wound healing leading to successful closure in the vast majority of cases. The recent introduction of vascularized rotational flaps has further improved outcomes in several series. However, there remains an overall 10% failure rate, which may increase as skull-base approaches continue to expand. These problems have catalyzed a search for a repair method that can be applied endoscopically and is capable of producing instant, watertight tissue bonds. Laser tissue welding has been advanced as one such technology that may satisfy these criteria and further reduce the morbidity and failure rate of cranial-base reconstruction.
Since their invention in the late 1950s, lasers have been successfully used in a variety of medical fields as both diagnostic and therapeutic instruments. As early as 1960, the potential for use of lasers in tissue adhesion was recognized. In 1962, Sigel and Acevado were the first to report the potential of thermal energy in tissue adhesion by using high-frequency electric current to create an end-to-side portocaval shunt in a canine model. Yahr and Strully adapted this concept to light energy and are credited with the first description of laser tissue welding for vascular anastomosis. The early work in laser tissue welding primarily used Nd:YAG (neodymium:yttrium-aluminum-garnet) systems. As technology advanced, a wider variety of laser systems entered the clinical armamentarium, including the argon, the carbon dioxide, and the diode laser, which allowed researchers to tailor the laser wavelength and depth of penetration to the tissue being studied. While these initial reports demonstrated the potential of laser tissue welding, in vivo applications were limited by suboptimal wound tensile strength and complications related to thermal leakage to surrounding healthy tissues.
A critical advance in laser tissue welding came over the last 2 decades with the introduction of biologic solder materials coupled with wavelength-specific chromophores, such as indocyanine green, fluorescein, and carbon black. These materials allowed for target-specific laser energy absorption and reduced the degree of collateral thermal leakage. Histologic analysis of wounds repaired using a biologic solder demonstrated that the direct thermal injury was restricted to the top 20 μm of the solder without any evidence of underlying tissue injury. This evidence of good target-specific characteristics is further supported by a study in an esophageal fistula model in which no thermal injury was noted in the esophageal mucosa following laser-assisted closure using an albumin-based solder. The chromophore provides a secondary benefit by providing a predictable color change, which established an objective basis of gauging adequacy of lasing. Some investigators have described a computer-based thermal feedback system to further define the lasing end point. However, its practical utility in light of the negligible thermal effect previously described remains to be seen.
Multiple combinations of biologic solders have been described, including collagen- and fibrin-based formulations. However, the most promising results have been reported using an albumin-based solution coupled with indocyanine green dye and hyaluronic acid. The use of biologic solders has also been shown to promote native wound-healing mechanisms. In contrast to the granulomatous inflammatory response seen with suture material, the lased solder provides a nonimmunogenic scaffold. This coagulum is gradually absorbed during the normal wound-healing process with minimal disruption of elastic fibers and a similar collagen density seen with traditional wound-closure techniques. A study in porcine dura reported integration of vascular and fibrous tissue into the repair within a week, demonstrating that normal wound healing is unimpeded by the solder-enhanced weld.
While a considerable amount of research has gone into optimizing laser-welding techniques in a variety of animal models, the precise mechanism of tissue bonding has yet to be fully explained. Most investigators agree that the application of laser energy results in a restructuring of the extracellular matrix with resultant interactions of native tissue proteins, including collagen interdigitation, and noncovalent laminin and entactin bonding. Murray and colleagues demonstrated a decrease in both a 235-kd guanidine-extractable protein and type VI collagen with a concomitant rise in protein aggregates with noncollagenous domains, suggesting that fibronectin is also involved. Although these studies have contributed to our grasp of the mechanism of laser tissue welding, a complete understanding remains confounded by multiple variables, including laser wavelength, tissue-specific energy absorption, and the use of a variety of solder and chromophore formulations.
Laser tissue welding using an albumin-based solder has been studied in a variety of tissues, including blood vessels, gut, nerves, skin, dura, bladder, and urethra. Despite our incomplete understanding of the mechanism, these studies have consistently confirmed that it is an efficacious method of tissue bonding capable of creating instant welds with significant tensile strength and high leak pressures. Barrieras and colleagues compared laser-welded pyeloplasty using an albumin/fibrin solder to both traditional suture and fibrin glue repair. This study found an immediate increase in anastomotic leak pressure using a laser weld over both suture and fibrin glue (37.2 ± 1.1 mm Hg as compared with 12.8 ± 4.0 mm Hg and 2.6 ± 1.1 mm Hg, respectively). In 1996, Foyt and colleagues performed one of the first ex vivo studies examining the utility of laser tissue welding in a head and neck application. This group looked at primary human cadaveric dural closure using an albumin/indocyanine green dye mixture. They reported a leak pressure of 26.2 ± 3.7 mm Hg with the laser closure as compared with 9.4 ± 1.7 mm Hg in the suture group. These studies underscore the fact that the efficacy of the weld depends on both the laser/solder combination as well as the tissue being addressed. The spectral absorption characteristics, extracellular matrix composition, and tensile properties of the underlying tissue all play an important role in the behavior of the lased coagulum. As a result, the validation of laser tissue welding as a reconstructive technique mandates preclinical studies that use a single laser/solder platform and address the tissues that are specifically relevant to cranial-base repair. While weld strength is the primary determinant of the utility of laser tissue welding, these studies must also address the prospective effects on wound healing as well as the risk of thermal injury inherent to the use of lasers in any clinical application.
The 808-nm diode laser coupled with a solder based on 42% human albumin, indocyanine green, and hyaluronic acid has been the most extensively studied in both animal and clinical trials and has thus become the basis of our investigations. In our initial study, our group demonstrated that laser tissue welding is capable of producing in sheep septal mucosa and periosteum burst strengths that were significantly higher than those of suture repair (mucosa: 34.88 ± 3.49 mm Hg versus 17.06 ± 1.83 mm Hg, P = .0001; periosteum: 30.02 ± 2.23 mm Hg versus 24.12 ± 0.71 mm Hg, P <.0001) ( Fig. 1 ). These data were used to establish an animal model in the New Zealand white rabbit to analyze the prospective behavior of these welds in the repair of a dorsal maxillary sinusotomy. This study found that laser welding was capable of achieving an immediate burst strength over four times that of normal human intracranial pressure. The strength of these bonds increased over the first 2 weeks and was noted to converge with those of an open wound left to heal by secondary intention by postoperative day 15 ( Fig. 2 ). This offers an interesting insight into the natural history of these wounds in a clinical setting, where it appears that native scarring and fibrosis alone are capable of sealing these defects within several weeks, confirming that efforts should be focused on preventing early repair failures. The other key finding of this study was that no thermal injury was noted to the surrounding tissues or underlying sinus mucosa ( Fig. 3 ). The lack of collateral thermal injury represents a critical attribute of laser tissue welding, especially when considering the proximity of these repairs to critical neurovascular structures. While not formally reported, the investigators also noted that, at the low irradiances required to effect these welds, the laser shows no clinical effect when applied directly to the tissue.
