Preclinical assessment of a modified Occlutech left atrial appendage closure device in a porcine model.

Left atrial appendage (LAA) closure is being developed as an alternative for stroke prevention in patients with atrial fibrillation that cannot tolerate long-term oral anticoagulation. To assess the feasibility, safety, and performance of a novel modified Occlutech LAA closure device in a preclinical porcine model, the modified Occlutech modified Occlutech Plus LAA closure device was implanted in 12 female pigs (25-39 kg body weight) under fluoroscopic and transesophageal echocardiography (TEE) guidance. Procedural and technical success, as well as safety of LAA closure, were evaluated peri-procedurally and after 4, 8, and 12 weeks. Moreover, after 4, 8 and, 12 weeks animals were sacrificed for pathological analysis (e.g., thrombus formation, device ingrowth, endothelialization, and inflammation). All LAA closure devices were successfully implanted. On follow-up, no serious adverse events such as device-associated thrombus or translocalization/embolization were observed. A clinically non-significant pericarditis was observed in 4 animals at the time of autopsy. Endothelialization of the device was visible after 4 weeks, advanced after 8 weeks and completed after 12 weeks. Immunohistochemistry showed low amounts of inflammatory infiltration on the edges of the device. The results of this study indicate that implantation of a modified Occlutech LAA closure device is feasible with rapid endothelialization and low inflammatory infiltration in a porcine model. Human data are needed to further characterize safety and efficacy.

Bionic approach for the prevention of exit-site infections of percutaneous devices.

Exit-site infections remain one of the main complications for percutaneous devices, such as catheters for peritoneal dialysis or drivelines for ventricular assist devices. Many efforts have been made to create a biological seal, yet without long-term success. This study investigates a new kind of percutaneous device which is coated with an extricable polymeric membrane. The bionic approach applies the naturally outwards directed growth of skin structures to technology: by pulling the protective membrane it slowly grows out of the body and a developing sulcus is exposed to dry air and an infection is avoided. In a feasibility study this kind of device was shown to reduce the rate of infection. To further investigate these devices, they were implanted in the skin of goats and observed for a period of more than 500 days. The membranes were pulled with a force of up to 2 N and the resulting movement was recorded. When being pulled, the membranes moved 0.4-0.9 mm per week, showing that the application of a continuously acting, defined force on the protective membrane causes the desired slow movement.

Percutaneous devices: a review of applications, problems and possible solutions.

Percutaneous devices enable the transfer of mass, energy and forces through the skin. There is a wide clinical need for this, which is not likely to decrease or disappear. The emerging new artificial organs, such as wearable kidneys or lungs, will be in increased demand in the future. Any application lasting longer than days or weeks is endangered by infections entering the body via the exit site. The only carefree solution that has been found is for an exit site placed on the skull, where it can be securely immobilized. For the majority of the locations on the abdomen or chest, no solution for an infection-free device has been found. A solution may be possible with a better understanding of the physiology of keratinocytes as a barrier for microbes.

How can we achieve infection-resistant percutaneous energy transfer?

Clinical records show ever increasing functional times of rotary blood pumps implanted in patients. With longer functional time, the problem of driveline infection is becoming more urgent. No material or scaffold has been found, which allows a permanent and stable ingrowth of skin cells that would prevent (pathogenic) germs entering the body. Usually, the epithelial cells die at the exit site and new cells form a sulcus around the driveline, which grows deeper and finally becomes infected. The purpose of this project is to present a solution to this problem by elaborating a new mechanism, the active skin-penetrating device. The device is composed of a tube with a 5-mm diameter, a protective sleeve that surrounds the catheter exit site, and an active traction device. The protective sleeve is made of thin polyurethane covered with polyethylenterephtalat (PET, i.e. Dacron) fibers to permit the attachment of keratinocytes, similar to the standard driveline. The active traction device exerts a constant pull on the protective sleeve. The ingrown keratinocytes slowly give way and the protective sleeve gradually moves out of the body at a rate of a few millimeters per week. Meanwhile, the keratinocytes transform into horny cells and are then shed as in natural skin. Therefore, the formation of a sulcus is avoided, and the protective sleeve remains infection-free. In a first proof of the concept, four of the new devices and 10 control devices were implanted in goats. The devices remained infection-free for a period of 420 days, whereas four of the 10 control devices became infected. On the basis of these experiments, the active skin-penetrating device has been further developed and is being tested again in goats in a refined version. The results so far indicate that with the active-skin penetrating device an infection-resistant percutaneous energy transfer can be achieved for a prolonged period of time.