An Implantable Magneto-Responsive Poly(aspartamide) Based Electrospun Scaffold for Hyperthermia Treatment.

When exposed to an alternating magnetic field, superparamagnetic nanoparticles can elicit the required hyperthermic effect while also being excellent magnetic resonance imaging (MRI) contrast agents. Their main drawback is that they diffuse out of the area of interest in one or two days, thus preventing a continuous application during the typical several-cycle multi-week treatment. To solve this issue, our aim was to synthesise an implantable, biodegradable membrane infused with magnetite that enabled long-term treatment while having adequate MRI contrast and hyperthermic capabilities. To immobilise the nanoparticles inside the scaffold, they were synthesised inside hydrogel fibres. First, polysuccinimide (PSI) fibres were produced by electrospinning and crosslinked, and then, magnetitc iron oxide nanoparticles (MIONs) were synthesised inside and in-between the fibres of the hydrogel membranes with the well-known co-precipitation method. The attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) investigation proved the success of the chemical synthesis and the presence of iron oxide, and the superconducting quantum interference device (SQUID) study revealed their superparamagnetic property. The magnetic hyperthermia efficiency of the samples was significant. The given alternating current (AC) magnetic field could induce a temperature rise of 5 °C (from 37 °C to 42 °C) in less than 2 min even for five quick heat-cool cycles or for five consecutive days without considerable heat generation loss in the samples. Short-term (1 day and 7 day) biocompatibility, biodegradability and MRI contrast capability were investigated in vivo on Wistar rats. The results showed excellent MRI contrast and minimal acute inflammation.

#Erasmus+ ­ or surgical research, development and innovation at the Department of Surgical Research and Techniques at Semmelweis University / #Erasmus+ - avagy sebészeti kutatás-fejlesztés és innováció a Semmelweis Egyetem Kísérletes és Sebészeti Mutéttani Tanszékén

The European Union is earmarking more and more resources each cycle to support research, development and innovation, and the projects set up by the working groups are helping to develop innovative solutions to reflecting societal issues of today. Since 2014, the Department of Surgical Research and Techniques of the Cardiovascular Center at Semmelweis University has been participating in international consortia supported by the Erasmus+ programme, which aim to modernise the teaching methodology of surgical training and to integrate IT technology into the training of surgical residents at pan-European level. This paper briefly summarises the international projects in which the Department has been involved over the last 7 years.

Adhesion stabilization in the early postoperative period in a rat model / Az adhézió stabilizálódásának meghatározása a korai posztoperatív idoszakban patkány modellen

Introduction: Adhesion formation is a complex series of events that results from cellular and molecular processes where, in contrast to the normal case, events that support adhesion genesis dominate over adhesion lysis. Tissue injury, haemorrhage, tissue desiccation and inflammatory processes, among others, play a role in its induction. Since the presence of adhesions can be associated with a number of negative complications, the primary aim is to prevent their development. There are several preventive targets for the process, but in many cases therapy is only provided immediately after the procedure. In this study, we present an experimental rat model of adhesion, where the aim is to understand the stabilization period of adhesion. All animals underwent the same surgical procedure, inducing tissue injury, minor haemorrhage and tissue desiccation, differing only in the timing of reoperations and sampling. On postoperative days 1­7, we assessed macroscopically and histopathologically the type of adhesions formed, the adhesive tissue, the stability of the adhesion. We found that stabilization was a process lasting several days, with unstable and moderately stable adhesions predominating by postoperative day 4. Knowing this allows to broaden the therapeutic window, targeting the most appropriate period in the early postoperative period, possibly combining treatments, to make adhesion prevention even more effective.

Peritoneum, the multifunctional membrane / Peritoneum, a multifunkcionális hártya

Introduction: Not only atraumatic surgical technique, precise bleeding control, removal foreign materials from the abdomen, but also avoiding desiccation or mechanical damage of peritoneal surface at abdominal surgery mean today evidence based expectation. Peritoneum with its extensive surface and special histological structure represents an important factor in normal physiological processes, furthermore as "Guard of abdomen" it has an important role to localise inflammatory reactions, useful as dialysing surface and provides also possibility for hyperthermic abdominal chemotherapy in tumour treatment. Largest part of peritoneal sac covers small intestine and colon. To prevent postoperative complications it is necessary to avoid desiccation of intestinal tract at laparoscopic and at open procedures as well ­ consequently "rehyration" is a routine recommendation today. Desiccation of intestinal tract results postoperative adhesions, furthermore damage of serosa will increase permeability of intestine wall and can result perforation. All the surgical recommendations suggest keeping intestine moist, whereas there are only a few real studies in surgical literature to support or to deny this theory. Our study reviews the pathophysiological and surgical respects of this situation and summarizes the results of latest researches of combined functions of peritoneum.

Early and late effects of absorbable poly(vinyl alcohol) hernia mesh to tissue reconstruction.

Hernia is a defect of the abdominal wall. Treatment is principally surgical mesh implantation. Non-degradable surgical meshes produce numerous complications and side-effects such as inflammatory response, mesh migration and chronic pain. In contrast, the biodegradable, poly (vinyl alcohol) (PVA) based polymers have excellent chemical, mechanical and biological properties and after their degradation no chronic pain can be expected. The toxicology of PVA solution and fibers was investigated with Human dermal fibroblast- Adult cell line. Implantation tests were observed on long-term contact (rat) and large animal (swine) models. To measure the adhesion formation, Diamond and Vandendael score were used. Macroscopical and histological responses were graded from the samples. In vitro examination showed that PVA solution and fibers are biocompatible for the cells. According to the implantation tests, all samples were integrated into the surrounding tissue, and there was no foreign body reaction. The average number of adhesions was found on the non-absorbable suture line. The biocompatibility of the PVA nanofiber mesh was demonstrated. It has a non-adhesive, non-toxic and good quality structure which has the potential to be an alternative solution for the part of the hernia mesh.

Poly(amino acid) based fibrous membranes with tuneable in vivo biodegradation.

In this work two types of biodegradable polysuccinimide-based, electrospun fibrous membranes are presented. One contains disulfide bonds exhibiting a shorter (3 days) in vivo biodegradation time, while the other one has alkyl crosslinks and a longer biodegradation time (more than 7 days). According to the mechanical measurements, the tensile strength of the membranes is comparable to those of soft the connective tissues and visceral tissues. Furthermore, the suture retention test suggests, that the membranes would withstand surgical handling and in vivo fixation. The in vivo biocompatibility study demonstrates how membranes undergo in vivo hydrolysis and by the 3rd day they become poly(aspartic acid) fibrous membranes, which can be then enzymatically degraded. After one week, the disulfide crosslinked membranes almost completely degrade, while the alkyl-chain crosslinked ones mildly lose their integrity as the surrounding tissue invades them. Histopathology revealed mild acute inflammation, which diminished to a minimal level after seven days.

An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice.

Mast cells have been shown to release extracellular vesicles (EVs) in vitro. However, EV-mediated mast cell communication in vivo remains unexplored. Primary mast cells from GFP-transgenic and wild type mice, were grown in the presence or absence of lipopolysaccharide (LPS), and the secreted EVs were separated from the conditioned media. Mast cell-derived EVs were next cultured with LPS-naïve mast cells, and the induction of TNF-α expression was monitored. In addition, primary mast cells were seeded in diffusion chambers that were implanted into the peritoneal cavities of mice. Diffusion chambers enabled the release of GFP+ mast cell-derived EVs in vivo into the peritoneal cavity. Peritoneal lavage cells were assessed for the uptake of GFP+ EVs and for TNF-α production. In vitro, LPS-stimulated mast cell-derived EVs were efficiently taken up by non-stimulated mast cells, and induced TNF-α expression in a TLR4, JNK and P38 MAPK dependent manner. In vivo, using implanted diffusion chambers, we confirmed the release and transmission of mast cell-derived EVs to other mast cells with subsequent induction of TNF-α expression. These data show an EV-mediated spreading of pro-inflammatory response between mast cells, and provide the first in vivo evidence for the biological role of mast cell-derived EVs.