New laser soldering-based closures: a promising method in natural orifice transluminal endoscopic surgery.

BACKGROUND: Complete closure of gastrotomy is the linchpin of safe natural orifice transgastric endoscopic surgery. OBJECTIVE: To evaluate feasibility and efficacy of a new method of gastrotomy closure by using a sutureless laser tissue-soldering (LTS) technique in an ex vivo porcine stomach. DESIGN: In vitro experiment. SETTING: Experimental laboratory. INTERVENTIONS: Histological analysis and internal and external liquid pressure with and without hydrochloric acid exposure were determined comparing gastrotomy closure with LTS and with hand-sewn surgical sutures. MAIN OUTCOME MEASUREMENTS: Comparison of LTS and hand-sewn surgical gastrotomy closure. The primary outcome parameter was the internal leak pressure. Secondary parameters were the difference between internal and external leak pressures, the impact of an acid environment on the device, histological changes, and feasibility of endoscopic placement. RESULTS: The internal liquid leak pressure after LTS was almost twice as high as after hand-sewn surgical closure (416 ± 53 mm Hg vs 229 ± 99 mm Hg; P = .01). The internal leak pressure (416 ± 53 mm Hg) after LTS was higher than the external leak pressure (154 ± 46 mm Hg; P < .0001). An acidic environment did not affect leak pressure after LTS. Endoscopic LTS closure was feasible in all experiments. Histopathology revealed only slight alterations beneath the soldering plug. LIMITATIONS: In vitro experiments. CONCLUSIONS: Leak pressure after LTS closure of gastrotomy is higher than after hand-sewn surgical closure. LTS is a promising technique for closure of gastrotomies and iatrogenic perforations. Further experiments, in particular survival studies, are mandatory.

Nanoshell assisted laser soldering of vascular tissue.

BACKGROUND AND OBJECTIVES: Laser tissue soldering (LTS) is a promising technique for tissue fusion but is limited by the lack of reproducibility particularly when the amount of indocyanine green (ICG) applied as energy absorber cannot be controlled during the soldering procedure. Nanotechnology enables the control over the quantitative binding of the ICG. The aim of this study was to establish a highly reproducible and strong tissue fusion using ICG packed nanoshells. By including the chromophore in the soldering scaffold, dilution of the energy absorber during the soldering procedure is prevented. The feasibility of this novel nanoshell soldering technique was studied by assessing the local heating of the area and tensile strength of the resulting fused tissue. STUDY DESIGN/MATERIALS AND METHODS: Nanoshells with a diameter of 250-270 nm were loaded with ICG and included in a porous polycaprolactone (PCL) scaffold doped with albumin solder. The nanoshell scaffold was used in a flexible, semi-dry formulation suitable for surgical use. Heat development, tensile strength as well as tissue damage were assessed. RESULTS: Rabbit aortic arteries were successfully soldered using an ICG packed nanoshell scaffold. Tensile strengths of these nanoshell soldered anastomoses were found to be 734 ± 327 mN (median = 640 mN). Thermal damage was restricted to the adventitia at the irradiated area. In addition, absorber dilution was prevented during the soldering procedure resulting in significantly lower variance in maximum temperature (P = 0.03) compared to the classical liquid ICG soldering technique. CONCLUSION: Using nanoshells, controlled amounts of chromophore could successfully be bound into the polymer scaffold. Diode laser soldering of vascular tissue using ICG-nanoshell scaffolds leads to strong and reproducible tissue fusion. With optimally chosen settings of irradiation time, nanoshells coating and scaffold properties, our improved LTS procedure demonstrates the potential for a clinically applicable anastomosis technique.

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study.

BACKGROUND: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. METHODS: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. RESULTS: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 µg/mL to 25 µg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. CONCLUSION: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.

Tissue fusion, a new opportunity for sutureless bypass surgery.

Microsurgical suturing is the standard for cerebral bypass surgery, a technique where temporary occlusion is usually necessary. Non-occlusive techniques such as excimer laser-assisted non-occlusive anastomosis (ELANA) have certainly widened the spectrum of treatment of complex cerebrovascular situations, such as giant cerebral aneurysms, that were otherwise non-treatable. Nevertheless, the reduction of surgical risks while widening the spectrum of indications, such as a prophylactic cerebral bypass, is still a main aim, that we would like to pursue with our sutureless tissue fusion research. The primary concern in sutureless tissue fusion- and especially in tissue fusion of cerebral vessels- is the lack of reproducibility, often caused by variations in the thermal damage of the vessel. This has prevented this novel fusion technique from being applicable in daily surgical use. In this overview, we present three ways to further improve the laser tissue soldering technique.In the first section entitled "Laser Tissue Soldering Using a Biodegradable Polymer," a porous polymer scaffold doped with albumin (BSA) and indocyanine green (ICG) is presented, leading to strong and reproducible tensile strengths in tissue soldering. Histologies and future developments are discussed.In the section "Numerical Simulation for Improvement of Laser Tissue Soldering," a powerful theoretical simulation model is used to calculate temperature distribution during soldering. The goal of this research is to have a tool in hand that allows us to determine laser irradiation parameters that guarantee strong vessel fusion without thermally damaging the inner structures such as the intima and endothelium.In a third section, "Nanoparticles in Laser Tissue Soldering," we demonstrate that nanoparticles can be used to produce a stable and well-defined spatial absorption profile in the scaffold, which is an important step towards increasing the reproducibility. The risks of implanting nanoparticles into a biodegradable scaffold are discussed.Step by step, these developments in sutureless tissue fusion have improved the tensile strength and the reproducibility, and are constantly evolving towards a clinically applicable anastomosis technique.

Thermal model for optimization of vascular laser tissue soldering.

Laser tissue soldering (LTS) is a promising technique for tissue fusion based on a heat-denaturation process of proteins. Thermal damage of the fused tissue during the laser procedure has always been an important and challenging problem. Particularly in LTS of arterial blood vessels strong heating of the endothelium should be avoided to minimize the risk of thrombosis. A precise knowledge of the temperature distribution within the vessel wall during laser irradiation is inevitable. The authors developed a finite element model (FEM) to simulate the temperature distribution within blood vessels during LTS. Temperature measurements were used to verify and calibrate the model. Different parameters such as laser power, solder absorption coefficient, thickness of the solder layer, cooling of the vessel and continuous vs. pulsed energy deposition were tested to elucidate their impact on the temperature distribution within the soldering joint in order to reduce the amount of further animal experiments. A pulsed irradiation with high laser power and high absorbing solder yields the best results.

Solder doped polycaprolactone scaffold enables reproducible laser tissue soldering.

BACKGROUND AND OBJECTIVES: In this in vitro feasibility study we analyzed tissue fusion using bovine serum albumin (BSA) and Indocyanine green (ICG) doped polycaprolactone (PCL) scaffolds in combination with a diode laser as energy source while focusing on the influence of irradiation power and albumin concentration on the resulting tensile strength and induced tissue damage. MATERIALS AND METHODS: A porous PCL scaffold doped with either 25% or 40% (w/w) of BSA in combination with 0.1% (w/w) ICG was used to fuse rabbit aortas. Soldering energy was delivered through the vessel from the endoluminal side using a continuous wave diode laser at 808 nm via a 400 microm core fiber. Scaffold surface temperatures were analyzed with an infrared camera. Optimum parameters such as irradiation time, radiation power and temperature were determined in view of maximum tensile strength but simultaneously minimum thermally induced tissue damage. Differential scanning calorimetry (DSC) was performed to measure the influence of PCL on the denaturation temperature of BSA. RESULTS: Optimum parameter settings were found to be 60 seconds irradiation time and 1.5 W irradiation power resulting in tensile strengths of around 2,000 mN. Corresponding scaffold surface temperature was 117.4+/- 12 degrees C. Comparison of the two BSA concentration revealed that 40% BSA scaffold resulted in significant higher tensile strength compared to the 25%. At optimum parameter settings, thermal damage was restricted to the adventitia and its interface with the outermost layer of the tunica media. The DSC showed two endothermic peaks in BSA containing samples, both strongly depending on the water content and the presence of PCL and/or ICG. CONCLUSIONS: Diode laser soldering of vascular tissue using BSA-ICG-PCL-scaffolds leads to strong and reproducible tissue bonds, with vessel damage limited to the adventitia. Higher BSA content results in higher tensile strengths. The DSC-measurements showed that BSA denaturation temperature is lowered by addition of water and/or ICG-PCL.