Differences in the mechanical properties of intestinal tissue based on preservation freezing duration and temperature.

In this study, tissue samples were stress tested to determine if freezing duration and temperature alter their mechanical properties. Tissue samples taken from the small intestine of pigs were assigned to 5 groups: fresh tissue, -28.9 °C for 7 days, -62.2 °C for 7 days, -28.9 °C for 30 days, and -62.2 °C for 30 days. Tissue was stored in PBS for the assigned temperature and duration until testing occurred with the exception of fresh tissue which was tested at sample collection. Before testing, samples were thawed in a room temperature bath, and the thickness was measured. Samples were then mounted in a biaxial test system using four anchoring rakes. Each sample was pulled to a strain of 0.2 with the corresponding forces recorded. This cycle of relaxation to 0.2 strain was repeated 5 times per sample. The thickness and force values were used to find the first Piola-Kirchhoff stress experienced at 0.2 strain and the strain energy. The average stress values in the circumferential direction were: fresh tissue: 22.3 ± 9.85 kPa; -28.9 °C for 7 days: 37.8 ± 14.1 kPa; -62.2 °C for 7 days: 46.5 ± 19.0 kPa; -28.9 °C for 30 days: 46.4 ± 22.7 kPa; -62.2 °C for 30 days: 40.1 ± 19.5 kPa. The stress and strain energy values of frozen tissue were statistically higher than the fresh tissue, although no statistical difference was found by varying duration or temperature. Based on this result, we determined that freezing tissue at any of the tested temperatures or durations increases the stiffness of the thawed tissue. This possibly occurs due to the directional formation of ice, which increases ion concentrations and glycosaminoglycan (GAG) interactions near collagen fibrils.

Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome.

With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to-severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO2 value dropped below 70 mmHg, the PaO2 /FiO2 ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to-severe ARDS with tachycardia. The SpO2 and PaO2 of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks.

Preperitoneal insufflation pressure of the abdominal wall in a porcine model.

BACKGROUND: Most complications and adverse events during laparoscopic surgery occur during initial entry into the peritoneal cavity. Among them, preperitoneal insufflation occurs when the insufflation needle is incorrectly placed, and the abdominal wall is insufflated. The objective of this study was to find a range for static pressure which is low enough to allow placement of a Veress needle into the peritoneal space without causing preperitoneal insufflation, yet high enough to separate abdominal viscera from the parietal peritoneum. METHODS: A pressure test was performed on twelve fresh porcine carcasses to determine the minimum preperitoneal insufflation pressure and the minimum initial peritoneal cavity insufflation pressure. Each porcine model had five needle placement categories. One category tested the initial peritoneal cavity insufflation pressure beneath the umbilicus. The four remaining categories tested the preperitoneal insufflation pressure at four different anatomical locations on the abdomen that can be used for initial entry. The minimum initial insufflation pressures from each carcass were then compared to the preperitoneal insufflation pressures to obtain an optimal range for initial insufflation. RESULTS: Increasing the insufflation pressure increased the probability of preperitoneal insufflation. Also, there was a statistically significant difference (p < 0.05) between the initial peritoneal cavity insufflation pressures (8.83 ± 4.19 mmHg) and the lowest preperitoneal pressures (32.54 ± 7.84 mmHg) (mean ± SD). CONCLUSION: Pressures greater than 10 mmHg resulted in initial cavity insufflation and pressures greater than 20 mmHg resulted in preperitoneal insufflation in porcine models. By knowing the minimum pressure required to separate the layers of the abdominal wall, the risk of preperitoneal insufflation can be mitigated while obtaining safe and efficient entry into the peritoneal cavity. The findings in this research are not a guideline for trocar or Veress needle placement, but instead reveal preliminary data which may lead to more studies, technology, etc.

Development of a multi-patient ventilator circuit with validation in an ARDS porcine model.

PURPOSE: The COVID-19 pandemic threatens our current ICU capabilities nationwide. As the number of COVID-19 positive patients across the nation continues to increase, the need for options to address ventilator shortages is inevitable. Multi-patient ventilation (MPV), in which more than one patient can use a single ventilator base unit, has been proposed as a potential solution to this problem. To our knowledge, this option has been discussed but remains untested in live patients with differing severity of lung pathology. METHODS: The objective of this study was to address ventilator shortages and patient stacking limitations by developing and validating a modified breathing circuit for two patients with differing lung compliances using simple, off-the-shelf components. A multi-patient ventilator circuit (MPVC) was simulated with a mathematical model and validated with four animal studies. Each animal study had two human-sized pigs: one healthy and one with lipopolysaccharide (LPS) induced ARDS. LPS was chosen because it lowers lung compliance similar to COVID-19. In a previous study, a control group of four pigs was given ARDS and placed on a single patient ventilation circuit (SPVC). The oxygenation of the MPVC ARDS animals was then compared to the oxygenation of the SPVC animals. RESULTS: Based on the comparisons, similar oxygenation and morbidity rates were observed between the MPVC ARDS animals and the SPVC animals. CONCLUSION: As healthcare systems worldwide deal with inundated ICUs and hospitals from pandemics, they could potentially benefit from this approach by providing more patients with respiratory care.

Computational optimization of a novel atraumatic catheter for local drug delivery in coronary atherosclerotic plaques.

Early identification and treatment of high-risk plaques before they rupture, and precipitate adverse events constitute a major challenge in cardiology today. Computational simulations are a time- and cost-effective way to study the performance, and to optimize a system. The main objective of this work is to optimize the flow of a novel atraumatic local drug delivery catheter for the treatment of coronary atherosclerosis. The mixing and spreading effectiveness of a drug fluid was analyzed utilizing computational fluid dynamics (CFD) in a coronary artery model. The optimum infusion flow of the nanoparticle-carrying drug fluid was found by maximizing the drug volume fraction and minimizing drug velocity at the artery wall, while maintaining acceptable wall shear stress (WSS). Drug velocities between 15 m/s and 20 m/s are optimum for local drug delivery. The resulting parameters from this study will be used to fabricate customized prototypes for future in-vivo experiments.

Preliminary Evaluation of the Viability of Peritoneal Drainage Catheters Implanted in Rats for Extended Durations.

Purpose/Aim: In developing a novel peritoneal oxygenation therapy, catheters implanted into the peritoneal cavity became obstructed with omental tissue and prevented the infusion and removal of fluid from the peritoneal cavity. The obstruction of peritoneal catheters is a significant failure in researching various peritoneal treatments as further fluid administration is no longer possible. The purpose of this preliminary study was to determine the most effective catheter design for infusion and removal of fluid into the peritoneal cavity of rats. Materials and Methods: Four types of catheters were tested including the Jackson-Pratt, round fluted drain, flat fluted drain, and an original design. Three of each catheter type were surgically placed into the peritoneal cavity of rats (n = 12). In order to test the efficacy of each catheter, saline was infused and extracted twice daily. Catheters were scored on a weighted scale based on the amount of time they remained patent, the subjective force needed for extraction/infusion, and the amount of saline removed. Results: The round and flat fluted drain catheters remained patent for the full duration of the study (12 days) compared to the other models which failed after 7 days. These catheters also yielded a high average for extracted saline volume and an easy extraction/infusion. Conclusions: The round and flat fluted drain catheters were recognized as viable options to be used in rats for peritoneal drain studies of up to 12 days.

Design and Validation of a Biosensor Implantation Capsule Robot.

We have proposed a long-term, noninvasive, nonrestrictive method of delivering and implanting a biosensor within the body via a swallowable implantation capsule robot (ICR). The design and preliminary validation of the ICR's primary subsystem-the sensor deployment system-is discussed and evidence is provided for major design choices. The purpose of the sensor deployment system is to adhere a small biosensor to the mucosa of the intestine long-term, and the modality was inspired by tapeworms and other organisms that employ a strategy of mechanical adhesion to soft tissue via the combined use of hooks or needles and suckers. Testing was performed to refine the design of the suction and needle attachment as well as the sensor ejection features of the ICR. An experiment was conducted in which needle sharpness, needle length, and vacuum volume were varied, and no statistically significant difference was observed. Finally, preliminary testing, coupled with prior work within a live porcine model, provided evidence that this is a promising approach for implanting a biosensor within the small intestine.

Design of a Wireless Medical Capsule for Measuring the Contact Pressure Between a Capsule and the Small Intestine.

A wireless medical capsule for measuring the contact pressure between a mobile capsule and the small intestine lumen was developed. Two pressure sensors were used to measure and differentiate the contact pressure and the small intestine intraluminal pressure. After in vitro tests of the capsule, it was surgically placed and tested in the proximal small intestine of a pig model. The capsule successfully gathered and transmitted the pressure data to a receiver outside the body. The measured pressure signals in the animal test were analyzed in the time and frequency domains, and a mathematic model was presented to describe the different factors influencing the contact pressure. A novel signal processing method was applied to isolate the contraction information from the contact pressure. The result shows that the measured contact pressure was 1.08 ± 0.08 kPa, and the small intestine contraction pressure's amplitude and rate were 0.29 ± 0.046 kPa and 12 min-1. Moreover, the amplitudes and rates of pressure from respiration and heartbeat were also estimated. The successful preliminary evaluation of this capsule implies that it could be used in further systematic investigation of small intestine contact pressure on a mobile capsule-shaped bolus.

Design and preliminary evaluation of a self-steering, pneumatically driven colonoscopy robot.

Colonoscopy is a diagnostic procedure to detect pre-cancerous polyps and tumours in the colon, and is performed by inserting a long tube equipped with a camera and biopsy tools. Despite the medical benefits, patients undergoing this procedure often complain about the associated pain and discomfort. This discomfort is mostly due to the rough handling of the tube and the creation of loops during the insertion. The overall goal of this work is to minimise the invasiveness of traditional colonoscopy. In pursuit of this goal, this work presents the development of a semi-autonomous colonoscopic robot with minimally invasive locomotion. The proposed robotic approach allows physicians to concentrate mainly on the diagnosis rather than the mechanics of the procedure. In this paper, an innovative locomotion approach for robotic colonoscopy is addressed. Our locomotion approach takes advantage of longitudinal expansion of a latex tube to propel the robot's tip along the colon. This soft and compliant propulsion mechanism, in contrast to minimally invasive mechanisms used in, for example, inchworm-like robots, has shown promising potential. In the preliminary ex vivo experiments, the robot successfully advanced 1.5 metres inside an excised curvilinear porcine colon with average speed of 28 mm/s, and was capable of traversing bends up to 150 degrees. The robot creates less than 6 N of normal force at its tip when it is pressurised with 90 kPa. This maximum force generates pressure of 44.17 mmHg at the tip, which is significantly lower than safe intraluminal human colonic pressure of 80 mmHg. The robot design inherently prevents loop formation in the colon, which is recognised as the main cause of post procedural pain in patients. Overall, the robot has shown great promise in an ex vivo experimental setup. The design of an autonomous control system and in vivo experiments are left as future work.

Intestinal Manometry Force Sensor for Robotic Capsule Endoscopy: An Acute, Multipatient In vivo Animal and Human Study.

GOAL: Development of a new medical device class generally termed robotic capsule endoscopes (RCE) is currently being pursued by multiple research groups. These maneuverable devices will allow minimally invasive diagnosis and treatment of intestinal pathologies. While the intraluminal pressures related to the migrating motor complex (MMC) are well understood, no previous study has measured the active contact forces exerted by the human small bowel wall on a solid, or near solid bolus such as an RCE. Understanding and quantifying the active contact force are critical for the advancement of RCE technology. METHODS: In this study, the authors develop a novel manometric contact force sensor for human studies and validate the feasibility of the design, sterilization method, and minimally invasive surgical procedure in a multianimal study, followed by a multihuman study. RESULTS: Four porcine tests of the sensor were conducted. The mean porcine myenteric contact force measured using the new sensor is 1.20 ± 0.08 N·cm-1. The mean myenteric contact force recorded for all five human test subjects is 0.18 ± 0.33 N·cm-1. CONCLUSION: This study demonstrates the feasibility of operating an MMC force sensor in a live human with a minimally invasive surgical technique and presents force data necessary for RCE design. SIGNIFICANCE: This study represents the first known myenteric contact force measurements on a solid bolus in the human small intestine.

A bio-inspired attachment mechanism for long-term adhesion to the small intestine.

To achieve long-term attachment of capsule endoscopes (CEs) and miniature biosensors in the human gastrointestinal (GI) tract, a tissue attachment mechanism (TAM) was designed, optimized and tested for safety and adhesive capabilities on excised tissue in vitro and in vivo on a live pig model. Six TAMs were tested for their attachment strength in an in vitro attachment tensile experiment in which each TAM was tested on three different proximal intestine tissue samples. The maximum strength and average value are 8.09 N and 4.54 N respectively. The initial attachment damage was tested for 10 min using a sine wave pull force on the TAM with a 0.4 N peak value and 6 s period, which represents typical human intestinal traction force from peristalsis. The in vitro attachment tensile test verified that the tissue was not visually damaged nor perforated by the attachment process. In the in vivo experiment, four TAMs were placed in the intestine of a pig through individual longitudinal enterotomies. X-ray images were taken each hour after the surgery and showed zero migration of the TAMs after 24 h of adhesion. X-ray images taken each day indicated the attachment duration of this mechanism lasted up to 6 days. Post experiment inspection confirmed the attachment did not cause visible damage to tissue. These results confirmed the reliability of the TAM in vivo and demonstrated preliminary feasibility of long-term sensor adhesion to the GI tract.

Design and Preliminary Experimental Investigation of a Capsule for Measuring the Small Intestine Contraction Pressure.

A tethered pressure measurement capsule was developed for measuring the small intestine contraction pressure to assist in locating capsules within the gastrointestinal (GI) tract and quantifying the contact force between the capsule and the small intestine lumen. The capsule was calibrated statically and dynamically in depth-controlled water at body temperature (37-38 °C). In vitro tests were performed on an intestinal simulator to verify the measurement function of the capsule. To perform a preliminary evaluation of its pressure measuring capabilities, the capsule was tested at a single location in a live pig model. The pressure signal from the live animal test was analyzed in the time domain, and then, the empirical mode decomposition and fast Fourier transformation were applied to analyze the contraction pressure and ambient pressure in the frequency domain. The contraction rate was 9.4 to 11.0 times per minute. The peak value of the contraction pressure was 0.24 ± 0.05 kPa. The successful test of this prototype lays the groundwork for a future untethered, swallowable version of the capsule, which will be capable of measuring dynamic pressures while in transit.

Evaluation of peritoneal microbubble oxygenation therapy in a rabbit model of hypoxemia.

Alternative extrapulmonary oxygenation technologies are needed to treat patients suffering from severe hypoxemia refractory to mechanical ventilation. We previously demonstrated that peritoneal microbubble oxygenation (PMO), in which phospholipid-coated oxygen microbubbles (OMBs) are delivered into the peritoneal cavity, can successfully oxygenate rats suffering from a right pneumothorax. This study addressed the need to scale up the procedure to a larger animal with a splanchnic cardiac output similar to humans. Our results show that PMO therapy can double the survival time of rabbits experiencing complete tracheal occlusion from 6.6 ±0.6 min for the saline controls to 12.2 ±3.0 min for the bolus PMO-treated cohort. Additionally, we designed and tested a new peritoneal delivery system to circulate OMBs through the peritoneal cavity. Circulation achieved a similar survival benefit to bolus delivery under these conditions. Overall, these results support the feasibility of the PMO technology to provide extrapulmonary ventilation for rescue of severely hypoxic patients.

Intestinal biomechanics simulator for robotic capsule endoscope validation.

This work describes the development and validation of a novel device which simulates important forces experienced by Robotic Capsule Endoscopes (RCE) in vivo in the small intestine. The purpose of the device is to expedite and lower the cost of RCE development. Currently, there is no accurate in vitro test method nor apparatus to validate new RCE designs; therefore, RCEs are tested in vivo at a cost of ∼$1400 per swine test. The authors have developed an in vitro RCE testing device which generates two peristaltic waves to accurately simulate the two biomechanical actions of the human small intestine that are most relevant to RCE locomotion: traction force and contact force. The device was successfully calibrated to match human physiological ranges for traction force (4-40 gf), contact force (80-500 gf) and peristaltic wave propagation speed (0.08-2 cm s(-1)) for a common RCE capsule geometry of 3.5 cm length and 1.5 cm diameter.

Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles.

Severe hypoxemia refractory to pulmonary mechanical ventilation remains life-threatening in critically ill patients. Peritoneal ventilation has long been desired for extrapulmonary oxygenation owing to easy access of the peritoneal cavity for catheterization and the relative safety compared to an extracorporeal circuit. Unfortunately, prior attempts involving direct oxygen ventilation or aqueous perfusates of fluorocarbons or hemoglobin carriers have failed, leading many researchers to abandon the method. We attribute these prior failures to limited mass transfer of oxygen to the peritoneum and have designed an oxygen formulation that overcomes this limitation. Using phospholipid-coated oxygen microbubbles (OMBs), we demonstrate 100% survival for rats experiencing acute lung trauma to at least 2 h. In contrast, all untreated rats and rats treated with peritoneal oxygenated saline died within 30 min. For rats treated with OMBs, hemoglobin saturation and heart rate were at normal levels over the 2-h timeframe. Peritoneal oxygenation with OMBs was therefore shown to be safe and effective, and the method requires less equipment and technical expertise than initiating and maintaining an extracorporeal circuit. Further translation of peritoneal oxygenation with OMBs may provide therapy for acute respiratory distress syndrome arising from trauma, sepsis, pneumonia, aspiration, burns and other pulmonary diseases.

Measurements of the contact force from myenteric contractions on a solid bolus.

The development of robotic capsule endoscopes (RCEs) is one avenue presently investigated by multiple research groups to minimize invasiveness and enhance outcomes of enteroscopic procedures. Understanding the biomechanical response of the small bowel to RCEs is needed for design optimization of these devices. In previous work, the authors developed, characterized, and tested the migrating motor complex force sensor (MFS), a novel sensor for quantifying the contact forces per unit of axial length exerted by the myenteron on a solid bolus. This work is a continuation, in which the MFS is used to quantify the contractile strength in the small intestine proximal, middle, and distal regions of five live porcine models. The MFSs are surgically implanted in a generally anesthetized animal, and force data from 5 min of dwell time are analyzed. The mean myenteric contact force from all porcine models and locations within the bowel is 1.9 ± 1.0 N cm(-1). Examining the results based on the small bowel region shows a statistically significant strengthening trend in the contractile force from proximal to middle to distal with mean forces of 1.2 ± 0.5, 1.9 ± 0.9, and 2.3 ± 1.0 N cm(-1), respectively (mean ± one standard deviation). Quantification of the contact force against a solid bolus provides developers of RCEs with a valuable, experimentally derived parameter of the intraluminal environment.

Small intestine mucosal adhesivity to in vivo capsule robot materials.

Multiple research groups are investigating the feasibility of miniature, swallowable, in vivo, untethered robots that are capable of traversing the small intestine for the purpose of acquiring biometrics and performing simple surgical procedures. A mathematical model of the intraluminal environment will speed the development of these so-called Robotic Capsule Endoscopes (RCEs), and to this end, the authors, in previous work, initiated a comprehensive program for characterizing both the active and passive forces exerted by the small intestine on an RCE-sized solid bolus. In this work, forces due to adhesivity between RCE materials and the mucosa are investigated. The experimental factors are adhesive modality (peel and tack), material (polycarbonate, micropatterned polydimethylsiloxane, stainless steel, and mucosa), and bowel region (proximal, middle, and distal). The mucosa is excised from a fasting pig, stored in lactated ringer's solution at 3 °C, and then tested at room temperature within 43 h of excision. The results show the mean tack strength of the mucosa to engineering materials was 0.198±0.070 mJ cm⁻². The mean peel strength was 0.055±0.016 mJ cm⁻². This study marks the first time, to the authors' knowledge, that adhesivity between small intestinal mucosa and RCE engineering materials has been measured. The adhesivity values acquired from this study will provide a valuable input into analytical and numerical models of the gastrointestinal tract, specifically models that account for the interfacial properties of the tissue.

Characterization and experimental results of a novel sensor for measuring the contact force from myenteric contractions.

The intraluminal pressures and traction forces associated with the migrating motor complex are well understood; however, the contact forces directly exerted by the bowel wall on a solid, or near solid, bolus have not previously been measured. Quantifying contact forces is an important component to understanding the net force experienced by an in vivo robotic capsule endoscope. In this paper, we develop a novel sensor, the migrating motor complex force sensor (MFS), for measuring the contact force generated by the contracting myenteron of the small intestine. The MFS consists of a perfused manometer connected to four torus-shaped balloons custom formed of natural latex rubber and embedded with temperature and pressure sensors. Force exerted on the balloon causes sensor pressure change. In vivo, the MFS measures the magnitude and axial location of contact pressure exerted by the myenteron. The device is tested in vivo in a live porcine model on the middle small bowel. The mean total force per centimeter of axial length of intestine that occurred over a 16-min interval in vivo was 1.04 N·cm (-1) in the middle region of the small intestine; the measured force is in the range of theoretical values.

Single-port-access surgery with a novel magnet camera system.

In this paper, we designed, built, and tested a novel single-port access laparoscopic surgery (SPA) specific camera system. This device (magnet camera) integrates a light source and video camera into a small, inexpensive, portable package that does not compete for space with the surgical tools during SPA. The device is inserted through a 26-mm incision in the umbilicus, followed by the SPA port, which is used to maintain an insufflation seal and support the insertion of additional tools. The camera, now in vivo, remains separate from the SPA port, thereby removing the need for a dedicated laparoscope, and, thus, allowing for an overall reduction in SPA port size or the use of a third tool through the insertion port regularly reserved for the traditional laparoscope. The SPA camera is mounted to the abdominal ceiling using one of the two methods: fixation to the SPA port through the use of a rigid ring and cantilever bar, or by an external magnetic handle. The purpose of the magnet camera system is to improve SPA by: 1) eliminating the laparoscope SPA channel; 2) increasing the field of view through enhanced camera system mobility; and 3) reducing interference between the camera system and the surgical tools at the port, both in vivo and ex vivo.