Eric Kramer

Temperature Measurement Methods During Direct Heat Arterial Tissue Fusion

Fusion of biological tissues through direct and indirect heating is a growing area of medical research, yet there are still major gaps in understanding this procedure. Several companies have developed devices which fuse blood vessels, but little is known about the tissues response to the stimuli. The need for accurate measurements of tissue behavior during tissue fusion is essential for the continued development and improvement of energy delivery devices. An experimental study was performed to measure the temperatures experienced during tissue fusion and the resulting burst pressure of the fused arteries. An array of thermocouples was placed in the lumen of a porcine splenic artery segment and sealed using a ConMed Altrus thermal fusion device. The temperatures within the tissue, in the device, and at the tissue-device interface were recorded. These measurements were then analyzed to calculate the temperature profile in the lumen of the artery. The temperature in the artery at the site of tissue fusion was measured to range from 142 to 163 °C using the ConMed Altrus. The corresponding burst pressure for arteries fused at this temperature was measured as 416 ± 79 mmHg. This study represents the first known experimental measurement of temperature at the site of vessel sealing found in the literature.

Tissue fusion bursting pressure and the role of tissue water content

Tissue fusion is a complex, poorly understood process which bonds collagenous tissues together using heat and pressure. The goal of this study is to elucidate the role of hydration in bond efficacy. Hydration of porcine splenic arteries (n=30) was varied by pre-fusion treatments: 24-48 hour immersion in isotonic, hypotonic, or hypertonic baths. Treated arteries were fused in several locations using Conmeds Altrus thermal fusion device and the bursting pressure was then measured for each fused segment. Artery sections were then weighed before and after lyophilization, to quantify water content. Histology (HE, EVG staining) enabled visualization of the bonding interface. Bursting pressure was significantly greater (p=4.17 E-ll) for the hypotonic group (607.6 ± 83.2mmHg), while no significant difference existed between the isotonic (332.6 ± 44.7mmHg) and hypertonic (348.7 ± 44.0mmHg) treatment groups. Total water content varied (p=8.80 E-24) from low water content in the hypertonic samples (72.5% weight ± 0.9), to high water content in the hypotonic samples (83.1% weight ± 1.9), while the isotonic samples contained 78.8% weight ± 1.1. Strength differences between the treated vessels imply that bound water driven from the tissue during fusion may reveal available collagen crosslinking sites to facilitate bond formation during the fusion process. Thus when the tissue contains greater bound water volumes, more crosslinking sites may become available during fusion, leading to a stronger bond. This study provides an important step towards understanding the chemistry underlying tissue fusion and the mechanics of tissue fusion as a function of bound water within the tissue.

A Novel Parameter for Predicting Arterial Fusion and Cutting in Finite Element Models

Current efforts to evaluate the performance of laparoscopic arterial fusion devices are limited to costly, time consuming, empirical studies. Thus, a finite element (FE) model, with the ability to predict device performance would improve device design and reduce development time and costs. This study introduces a model of the heat transfer through an artery during electrosurgical procedures that accounts for changes in thermal material properties due to water loss and temperature. Experiments then were conducted by applying a known heat and pressure to carefully sectioned pieces of porcine splenic arteries and measuring cut completeness. From this data, equations were developed to predict at which temperature and pressure arterial tissue is cut. These results were then incorporated into a fully coupled thermomechanical FE model with the ability to predict whole artery cutting. An additional experiment, performed to examine the accuracy of the model, showed that the model predicted complete artery cut results correctly in 28 of 32 tests. The predictive ability of this FE model opens a gateway to more advanced electrosurgical fusion devices and modeling techniques of electrosurgical procedures by allowing for faster, cheaper and more comprehensive device design.

Bond Strength of Thermally Fused Vascular Tissue Varies With Apposition Force

Surgical tissue fusion devices ligate blood vessels using thermal energy and coaptation pressure, while the molecular mechanisms underlying tissue fusion remain unclear. This study characterizes the influence of apposition force during fusion on bond strength, tissue temperature, and seal morphology. Porcine splenic arteries were thermally fused at varying apposition forces (10-500 N). Maximum bond strengths were attained at 40 N of apposition force. Bonds formed between 10 and 50 N contained laminated medial layers; those formed above 50 N contained only adventitia. These findings suggest that commercial fusion devices operate at greater than optimal apposition forces, and that constituents of the tunica media may alter the adhesive mechanics of the fusion mechanism.

Energy-Based Tissue Fusion for Sutureless Closure: Applications, Mechanisms, and Potential for Functional Recovery

As minimally invasive surgical techniques progress, the demand for efficient, reliable methods for vascular ligation and tissue closure becomes pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. Although the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used across devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue effect. Furthermore, energy-based techniques exhibit promise for the closure and functional repair of soft and connective tissues in the nervous, enteral, and dermal tissue domains. A constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required in order to optimize and progress the use of energy-based tissue fusion. While rapid tissue bonding has been suggested to arise from dehydration, dipole interactions, molecular cross-links, or the coagulation of cellular proteins, long-term functional tissue repair across fusion boundaries requires that the reaction to thermal damage be tailored to catalyze the onset of biological healing and remodeling. In this review, we compile and contrast findings from published thermal fusion research in an effort to encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.

A Small Deformation Thermoporomechanics Finite Element Model and Its Application to Arterial Tissue Fusion

Understanding the impact of thermally and mechanically loading biological tissue to supraphysiological levels is becoming of increasing importance as complex multiphysical tissue-device interactions increase. The ability to conduct accurate, patient specific computer simulations would provide surgeons with valuable insight into the physical processes occurring within the tissue as it is heated or cooled. Several studies have modeled tissue as porous media, yet fully coupled thermoporomechanics (TPM) models are limited. Therefore, this study introduces a small deformation theory of modeling the TPM occurring within biological tissue. Next, the model is used to simulate the mass, momentum, and energy balance occurring within an artery wall when heated by a tissue fusion device and compared to experimental values. Though limited by its small strain assumption, the model predicted final tissue temperature and water content within one standard deviation of experimental data for seven of seven simulations. Additionally, the model showed the ability to predict the final displacement of the tissue to within 15% of experimental results. These results promote potential design of novel medical devices and more accurate simulations allowing for scientists and surgeons to quickly, yet accurately, assess the effects of surgical procedures as well as provide a first step toward a fully coupled large deformation TPM finite element (FE) model.

Strength and Persistence of Energy-Based Vessel Seals Rely on Tissue Water and Glycosaminoglycan Content.

Vessel ligation using energy-based surgical devices is steadily replacing conventional closure methods during minimally invasive and open procedures. In exploring the molecular nature of thermally-induced tissue bonds, novel applications for surgical resection and repair may be revealed. This work presents an analysis of the influence of unbound water and hydrophilic glycosaminoglycans on the formation and resilience of vascular seals via: (a) changes in pre-fusion tissue hydration, (b) the enzymatic digestion of glycosaminoglycans (GAGs) prior to fusion and (c) the rehydration of vascular seals following fusion. An 11% increase in pre-fusion unbound water led to an 84% rise in vascular seal strength. The digestion of GAGs prior to fusion led to increases of up to 82% in seal strength, while the rehydration of native and GAG-digested vascular seals decreased strengths by 41 and 44%, respectively. The effects of increased unbound water content prior to fusion combined with the effects of seal rehydration after fusion suggest that the heat-induced displacement of tissue water is a major contributor to tissue adhesion during energy-based vessel sealing. The effects of pre-fusion GAG-digestion on seal integrity indicate that GAGs are inhibitory to the bond formation process during thermal ligation. GAG digestion may allow for increased water transport and protein interaction during the fusion process, leading to the formation of stronger bonds. These findings provide insight into the physiochemical nature of the fusion bond, its potential for optimization in vascular closure and its application to novel strategies for vascular resection and repair.

A novel parameter for predicting arterial fusion and ablation in finite element models

Tissue fusion devices apply heat and pressure to ligate or ablate blood vessels during surgery. Although this process is widely used, a predictive finite element (FE) model incorporating both structural mechanics and heat transfer has not been developed, limiting improvements to empirical evidence. This work presents the development of a novel damage parameter, which incorporates stress, water content and temperature, and demonstrates its application in a FE model. A FE model, using the Holzapfel-Gasser-Ogden strain energy function to represent the structural mechanics and equations developed by Cezo to model water content and heat transfer, was created to simulate the fusion or ablation of a porcine splenic artery. Using state variables, the stresses, temperature and water content are recorded and combined to create a single parameter at each integration point. The parameter is then compared to a critical value (determined through experiments). If the critical value is reached, the element loses all strength. If the value is not reached, no change occurs. Little experimental data exists for validation, but the resulting stresses, temperatures and water content fall within ranges predicted by prior work. Due to the lack of published data, additional experimental studies are being conducted to rigorously validate and accurately determine the critical value. Ultimately, a novel method for demonstrating tissue damage and fusion in a FE model is presented, providing the first step towards in-depth FE models simulating fusion and ablation of arteries.

The role of glycosaminoglycans in tissue adhesion during energy-based vessel sealing

Energy-based vessel sealing remains a common alternative to traditional mechanical ligation procedures, despite considerable uncertainty as to the origin and stability of vascular adhesion forces. Evidence of conformal changes in Collagen IA has fostered support of denatured collagen as the origin of tissue adhesion; experimental observation suggests that while pure collagen fails to adhere, remaining vascular constituents play a critical adhesive role. This study initiates a constitutive model of adhesion forces in thermal fusion by determining the effects of glycosaminoglycan (GAG) content on the bursting pressure of thermally sealed vessels. GAG content of porcine splenic arteries was progressively altered via pre-fusion treatment in Chondroitinase ABC (ChABC) for 0-5h at 1U/mL (n=10/gp.), followed by fusion with the ConMed ALTRUS® thermal fusion device and subsequent strength testing. Sulfated GAG (sGAG) concentrations as quantified by the Dimethylmethylene Blue (DMMB) assay were reduced in ChABC-treated vessels (5h) by 73.8 ± 4.2 % as compared with untreated tissue. Bursting pressures of ChABC-treated vessels (5h) were significantly greater than those of control vessels (800.33 ± 54.34 mmHg and 438.40 ± 51.81 mmHg respectively, p=2.0e-04). Histology enabled qualitative visualization of the treated arterial cross-section and of the bonding interface. The negative correlation between GAG content and arterial seal strengths suggests that by resisting water transport, arterial GAG presence may inhibit adhesive interactions between adjacent cellular tissue layers during energy-based vessel sealing. By elucidating the components which facilitate or inhibit adhesion in thermal vessel sealing, this study provides an important step towards understanding the chemistry underlying fusion and evaluating its potential for expansion to avascular tissues.

Tissue Hydration Influences Bursting Pressure of Fused Arteries

Tissue fusion is a complex thermally driven reaction which, through the application of heat and pressure, bonds the extracellular matrix (ECM) of neighboring tissues together. While the mechanism of this reaction is unknown, several theories do exist. Collagen is largely thought to be responsible for the formation of the fusion bond [1–3]. During tissue fusion, as the tissue temperature is elevated (> 100 °C) [4–5], collagen denatures and water is forcibly evaporated out of the tissue [6–11]. Collagen in arterial tissue is comprised of a tightly wound triple helix held in place by crosslinking. Upon denaturation, the crosslinks are broken and the helix unwinds [6–8]. It is theorized that under applied heat and pressure the denatured molecules tangling with adjacent molecules [1], crosslinking to neighboring molecules [2], or a combination of these two mechanisms are responsible for the formation of the tissue fusion bond [3]. Water is also present in the ECM which can be classified as free or bound. Free water is able to diffuse and move freely around the ECM. Bound water is held to ECM proteins through dipole interactions. During tissue fusion, the water is forcibly removed and these charged sites which interact with water are now able to interact with adjacent molecules. These charged sites would not exist if not for the removal of water from the ECM. The goal of this study is to elucidate the importance of water in the formation of the tissue fusion bond.Copyright