Sutureless ophthalmic surgery: a scaffold-enhanced bioadhesive technique.

PURPOSE: Bioadhesives have had limited use in ophthalmic surgery. Problems with these adhesives have included inadequate tensile strength and difficulty with their application to the tissue site. We evaluated a scaffold-enhanced cyanoacrylate bioadhesive composite as an alternative to sutures in ophthalmic surgery, including strabismus procedures. METHODS AND MATERIALS: The bioadhesive composite consisted of 2-octyl-cyanoacrylate combined with either a poly(L-lactic-co-glycolic acid) (PLGA) scaffold or a rehydrated porcine small intestine submucosa (SIS) scaffold. Extraocular rectus muscle and sclera were obtained from rabbits (n = 40) and were used, with these bioadhesive composites, to produce rectus muscle-to-sclera, sclera-to-sclera, and rectus muscle-to-rectus muscle adhesions. Control adhesions were created with cyanoacrylate only. The breaking load of the tissue repair was measured with a material strength-testing machine. RESULTS: In all cases, the scaffold-enhanced cyanoacrylate adhesions were significantly stronger (P < 0.001) than the cyanoacrylate alone. The rectus muscle-to-sclera adhesions were greater than the in vivo forces reported for the horizontal rectus muscles in humans in extreme gaze. CONCLUSION: This scaffold-enhanced bioadhesive composite produced initial muscle-sclera adhesions with strength satisfactory for strabismus surgery. It also may be applicable to other categories of ophthalmic surgery as a substitute for sutures.

A new technique of tissue repair for ophthalmic surgery.

Ophthalmic surgery currently utilizes suture materials to repair wounds created during eye operations. Although effective, suture-based techniques can result in complications that further impair the patient's vision, such as retinal detachment and scleral perforation associated with strabismus (eye muscle) surgery. Two techniques currently under development avoid sutures altogether, yielding similar strength results, reduced operating time, and simpler methods of repair. The first of these techniques employs a light-activated scaffold-enhanced protein solder to re-adhere the tissue. The second technique utilizes commercially available bioadhesives that have been scaffold-enhanced to improve their handling characteristics. A comparison of these two techniques is given. Initial tensile strength results show a higher strength of repair when a scaffold is utilized, with significantly less variations within each experimental group. Repairs formed using the scaffold-enhanced cyanoacrylate adhesives were the strongest. The tensile strength of extraocular muscle-to-sclera adhesions was 72% stronger than cyanoacrylate alone (4.2 +/- 0.2 N vs. 2.4 +/- 0.4 N) and 78% stronger than native tissue (2.3 +/- 0.4 N). Sclera-to-sclera adhesions were 60% stronger than adhesions formed with cyanoacrylate alone (3.9 +/- 0.2 N vs. 2.5 +/- 0.4 N), while the tensile strength of extraocular muscle-to-extraocular muscle adhesions were 81% of native extraocular muscle tensile strength (5.6 +/- 0.2 N vs. 6.2 +/- 0.3 N), and 50% stronger than adhesions formed using cyanoacrylate alone (3.6 +/- 0.4 N). The data analysis and resulting conclusions favor the less invasive adhesive technique as an alternative for tissue reattachment during ophthalmic procedures. Future experiments will examine the optimization of application parameters and detail tensile strength time course studies.

A light-activated surgical adhesive technique for sutureless ophthalmic surgery.

OBJECTIVE: To investigate a scaffold-enhanced, light-activated bioadhesive technique as a substitute for sutures in ophthalmic surgery. CLINICAL RELEVANCE: Suture use in ophthalmic surgery is technically demanding and time consuming and may be associated with serious complications such as inadvertent ocular penetration, which can result in retinal detachment and endophthalmitis. Bioadhesive surgery could eliminate many complications and limitations associated with the use of sutures. METHODS: The bioadhesive was composed of a poly(L-lactic-co-glycolic acid) (PLGA) porous scaffold doped with a protein solder mix composed of serum albumin and indocyanine green, which was activated with a diode laser. Extraocular rectus muscle-to-extraocular rectus muscle, sclera-to-sclera, and extraocular rectus muscle-to-sclera adhesions were created in freshly harvested tissue followed by tensile-strength testing of these surgical adhesions. RESULTS: Optimum tensile strength for muscle-to-muscle repair was achieved with 50% wt/vol bovine serum albumin and 0.5 mg/mL of indocyanine green saturated into a PLGA porous scaffold and activated with an 808-nm diode laser. The tensile strength was 81% of the native muscle's tensile strength (mean +/- SD, 433 +/- 70 g vs 494 +/- 73 g). Sclera-to-sclera adhesions achieved a mean +/- SD tensile strength of 295 +/- 38 g, whereas that for extraocular rectus muscle-to-sclera adhesions was 309 +/- 37 g. CONCLUSION: Sutureless surgery using this bioadhesive technique for various ophthalmic procedures appears feasible and may result in reduced surgical complications and cost.

Scaffold-enhanced albumin and n-butyl-cyanoacrylate adhesives for tissue repair: ex vivo evaluation in a porcine model.

An ex vivo study was conducted in a porcine model to compare the tensile strength of tissue samples repaired by three different repair methods: (i) scaffold-enhanced light-activated albumin protein solder, (ii) scaffold-enhanced n-butyl-cyanoacrylate adhesive, and (iii) conventional sutures. Biodegradable polymer scaffolds of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and salt particles using a solvent-casting and particulate-leaching technique. Repairs were conducted on seventeen different tissues including the carotid, femoral, splenic, coronary, and pulmonary arteries, aorta, small intestine, ureter, sciatic nerve, spleen, atrium, kidney, muscle, skin, lung, liver and pancreas. Acute breaking strengths were measured and the data were analyzed by Student's T-test. The resultant repairs using the scaffold-enhanced light-activated adhesive (Group I) were found to yield equivalent tensile strengths to conventional sutures (Group III), with significantly smaller mean standard deviations (8% vs. 25%). The cyanoacrylate-doped scaffold (Group II) repairs performed extremely well with tensile strengths approximately 30% higher for organ tissue and approximately 20% higher for vascular tissue than with the other two repair techniques evaluated in this study. The addition of the polymer scaffold assists in tissue alignment and reduces problems associated with adhesive runaway from the repair site. With appropriate packaging, scaffold-enhanced adhesives offer the potential for quick application in the field by less skilled professionals, paraprofessionals and bystanders in emergency situations--both military and civilian--outside a hospital or clinic setting.

Absorption properties of alternative chromophores for use in laser tissue soldering applications.

The feasibility of using alternative chromophores in laser tissue soldering applications was explored. Two commonly used chromophores, indocyanine green (ICG), and methylene blue (MB) were investigated, as well as three different food colorings: red #40 (RFC), blue #1 (BFC), and green consisting of yellow #5 and blue #1 (GFC). Three experimental studies were conducted: (i) The absorption profiles of the five chromophores, when diluted in deionized water and when bound to protein, were recorded; (ii) the effect of accumulated thermal dosages on the absorption profile of the chromophores was evaluated; and (iii) the stability of the absorption profiles of the chromophore-doped solutions when exposed to ambient light for extended time periods was measured. The peak absorption wavelengths of ICG, MB, RFC, and BFC, were found to be 805 nm, 665 nm, 503 nm, and 630 nm respectively in protein solder. The GFC had two absorption peaks at 426 nm and 630 nm, corresponding to the two dye components comprising this color. The peak absorption wavelength of ICG and MB was dependent on the choice of solvent (deionized water or protein). In contrast, the peak absorption wavelengths of the three chromophores were not dependent on the choice of solvent. ICG and MB showed a significant decrease in absorbance units with increased time and temperature when heated to temperature up to 100 degrees C. A significant decrease in the absorption peak occurred in the ICG and MB samples when exposed to ambient light for a period of 7 days. Negligible change in absorption with accumulated thermal dose up to 100 degrees C or light dose (over a period of 84 days) was observed for any of the three food colorings investigated.

Effect of varying chromophores used in light-activated protein solders on tensile strength and thermal damage profile of repairs.

Clinical adoption of laser tissue welding (LTW) techniques has been beleaguered by problems associated with thermal damage of tissue and insufficient strength of the resulting tissue bond. The magnitude of these problems has been significantly reduced with the incorporation of indocyanine green (ICG)-doped protein solders into the LTW procedure to form a new technique known as laser tissue soldering (LTS). With the addition of ICG, a secondary concern has arisen relating to the potential harmful effects of the degradation products of the chromophore upon thermal denaturation of the protein solder with a laser. In this study, two different food colorings were investigated, including blue #1 and green consisting of yellow #5 and blue #1, as alternative chromophores for use in LTS techniques. Food coloring has been found to have a suitable stability and safety profile for enteral use when heated to temperatures above 200 degrees C; thus, it is a promising candidate chromophore for LTS which typically requires temperatures between 50 degrees C and 100 degrees C. Experimental investigations were conducted to test the tensile strength of ex vivo repairs formed using solders doped with these alternative chromophores in a bovine model. Two commonly used chromophores, ICG and methylene blue (MB), were investigated as a reference. In addition, the temperature rise, depth of thermal coagulation in the protein solder, and the extent of thermal damage in the surrounding tissue were measured. Temperature rise at the solder/tissue interface, and consequently the degree of solder coagulation and collateral tissue thermal damage, was directly related to the penetration depth of laser light in the protein solder. Variation of the chromophore concentration such that the laser light penetrated to a depth approximately equal to half the thickness of the solder resulted in uniform results between each group of chromophores investigated. Optimal tensile strength of repairs was achieved by optimizing laser and solder parameters to obtain a temperature of approximately 65 degrees C at the solder/tissue interface. The two alternative chromophores tested in this study show considerable promise for application in LTS techniques, with equivalent tensile strength to solders doped with ICG or MB, and the potential advantage of eliminating the risks associated with harmful byproducts.

Optimal parameters for arterial repair using light-activated surgical adhesives.

The clinical acceptance of laser-tissue repair techniques is dependent on the reproducibility of viable repairs. Reproducibility is dependent on two factors: (i) the choice of materials to be used as the adhesive; and (ii) obtaining temperatures high enough to cause protein denaturation at the vital tissue interface without causing excessive thermal damage to the surrounding tissue. The use of a polymer scaffold as a carrier for the protein solder provides for uniform application of the solder to the tissue, thus allowing for pre-selection of optimal laser parameters. The scaffold also facilitates precise tissue alignment and ease of clinical application. In addition, the scaffold can be doped with various pharmaceuticals such as hemostatic and thrombogenic agents to aid wound healing. An ex vivo study was performed to correlate solder and tissue temperature with the tensile strength of arterial repairs formed using scaffold-enhanced light-activated surgical adhesives. Previous studies by our group using solid protein solder without the scaffold indicate that a solder/tissue, interface temperature of 65 degrees C is optimal. Using this parameter as a benchmark, laser irradiance was varied and temperatures were recorded at the surface and at the tissue interface of scaffold-enhanced protein solder using an infrared temperature monitoring system, designed by the researchers, and a type-K thermocouple, respectively.

Solubility studies of albumin protein solders used for laser-assisted tissue repair.

Albumin protein solders used for light-activated tissue repair are soluble in physiological fluids prior to laser irradiation. Inevitably, some of the material tends to run away before it can be bonded to the tissue. In addition, blood dilution alters the mechanical properties of the solder. Consequently, the strength of the repair is compromised resulting in poor reproducibility and reliability of the repair technique. The emerging use of solder-doped polymer membranes offers a potential solution to this problem. Predenaturation of the solder in a hot water bath also holds promise as a method for reducing initial solder solubility. The purpose of this study was to determine if polymer reinforcement and/or predenaturation could reduce the solubility of albumin protein solders, and thus, the ultimate breaking strength of incisions repaired by means of laser soldering techniques. A Bradford protein assay was utilized to measure the solubility of the protein solders prior to and after thermal denaturation. The results of this comparison showed that doping of the solder in a polymer membrane and predenaturation of the solders at 75 degrees C were advantageous for improving their handling characteristics. Alteration of the mechanical properties of the solders prior to laser treatment was also prevented, thus improving the reproducibility and reliability of the repairs.

Use of an infrared temperature monitoring system to determine optimal temperature for laser-solder tissue repair.

Thermal damage of tissue is a major concern for all laser tissue repair techniques where the resulting strength of a repair is sensitive to slight alterations in tissue temperature as well as changes in the duration of exposure of the tissue to the laser beam. Too low of a temperature will prevent proper bonding between the surfaces while prolonged exposure of the tissue to the laser beam results in collateral thermal damage and decreased flexibility and strength of the repair. Temperature feedback systems that monitor the surface temperature of the repair site and adjust the laser irradiance accordingly increase the success rate of the technique. Knowledge of an optimal temperature for tissue soldering will also increase the reliability of the technique. The choice of solder material has been another challenge to the reproducibility of strong repairs. The emerging use of solder-doped polymer membranes as surgical adhesives offers numerous advantages over more traditional liquid and solid solders. Poly (L-lactic-co-glycolic acid) (PLGA), when used as a polymer scaffold, is porous enough to absorb serum albumin and can also be doped with various hemostatic and thrombogenic agents to aid tissue healing. An in vitro study was performed to correlate tissue temperature with the tensile strength of repairs formed using the solder-doped polymer membranes. Previous studies by our group indicate that a solder/tissue interface temperature of 65 degrees C is optimal. Using this parameter as a bench mark, laser irradiance was varied and the solder surface and solder/tissue interface temperatures were monitored by an IR temperature monitoring system, designed by the researchers, and a type K thermocouple, respectively.

Optimization of laser-solder repair technique for possible application in strabismus surgeries.

Strabismus is the lack of binocular vision due to an inability to control one of the eye muscles. Corrective surgery is the most common recourse and consists of adjusting and reattaching the extraocular muscle to the sclera. In approximately 10% of cases involving re-insertment of the extraocular muscle via suture techniques, the needle is inserted too deeply into the eye resulting in perforation of the retina. Fibrin glues and cyanoacrylates have been substituted with unsatisfactory mechanical results. The goal of this study was to maximize the tensile strength of rabbit extraocular muscles repaired using a laser-solder technique developed by McNally et al., Biodegradable polymer membranes of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and salt particles using a solvent-casting and particulate-leaching technique. The porous membranes were doped with protein solder composed of 25% and 50% (w/v) serum albumin and 0.5 mg/ml indocyanine green (ICG) dye mixed in deionized water. In vitro tissue specimens were repaired using the solder-doped polymer membranes in conjunction with an 805 nm diode laser. The tensile strength was tested on an MTS machine and results were analyzed with the Student's T-test.

Biodegradable synthetic polymer scaffolds for reinforcement of albumin protein solders used for laser-assisted tissue repair.

Laser tissue soldering has been investigated for several years by researchers in our laboratory as an alternative to conventional tissue fasteners, including sutures, staples and clips. Laser tissue soldering is a bonding technique in which protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. Over the past four years we have been investigating the use of synthetic polymer membranes as a means for reinforcing the strength of tissue repairs formed using traditional laser tissue soldering techniques. The purpose of this study was to assess the influence of various processing parameters on the strength of tissue repairs formed using the reinforced solder. Biodegradable polymer membranes of specific porosity were fabricated by means of a solvent-casting and particulate-leaching technique, using three different poly(alpha ester)s: polyglycolic acid (PGA), polylactic acid (PLA) and poly(L-lactic-co-glycolic acid) (PLGA). In addition, several membranes were also prepared with poly(ethylene glycol) (PEG). The membranes were then doped with the traditional protein solder mixture of serum albumin and indocyanine green dye. Varied processing parameters included the polymer type, the PLGA copolymer blend ratio, the polymer/PEG blend ratio, the porosity of the polymer membrane and the initial albumin weight fraction. Variation of the polymer type had negligible effect on the strength of the repairs. Although it is known that alteration of the copolymer blend ratio of PLGA influences the degradation rate of the polymer, this variation also had no significant effect on the strength of the repairs formed. Increased membrane flexibility was observed when PEG was added during the casting stage. An increase in the porosity of the polymer membranes led to a subsequent increase in the final concentration of protein contained within the membranes, hence aiding in strengthening the resultant repairs. Likewise, an increase in the initial albumin weight fraction increased the strength of the resultant repairs.