Smart knives: controlled cutting schemes to enable advanced endoscopic surgery

With the backdrop of the rapidly developing research in Natural Orifice Transluminal Endoscopic Surgery (NOTES), analysis of the literature supported the view that inventing new, controlled tissue dissection methods for flexible endoscopic surgery may be necessary. The literature also confirmed that white space exists for research into and the development of new cutting tools. The strategy of “deconstructing dissection” proposed in this thesis may provide dissection control benefits, which may help address the unique manoeuvring challenges for tissue dissection at flexible endoscopy. This assertion was supported by investigating six embodiments of the strategy which provided varying degrees of enhanced tissue dissection control. Seven additional concepts employing the strategy which were not prototyped also were offered as potential solutions that eventually might contribute evidence in defence of the strategy. One concept for selective ablation — dye-mediated laser ablation — was explored in-depth by theoretical analysis, experimentation and computation. The ablation process was found to behave relatively similar to unmediated laser ablation, but also to depend on cyclic carbonisation for sustained ablation once the dye had disappeared. An Arrhenius model of carbonisation based on the pyrolysis and combustion of wood cellulose was used in a tissue ablation model, which produced reasonable results. Qualitative results from four methods for dye application and speculation on three methods for dye removal complete the framework by which dye-mediated laser ablation might deliver on the promise offered by “deconstructing dissection”. Overall, this work provided the “deconstructing dissection” strategic framework for controlled cutting schemes and offered plausible evidence that the strategy could work by investigating embodiments of the scheme. In particular, dye-mediated laser ablation can provide selective ablation of tissue, and a theoretical model for the method of operation was offered. However, some practical hurdles need to be overcome before it can be useful in a clinical setting

Inflammation and Corrosion in Total Hip Prostheses: The Generation and Interaction of Reactive Oxygen Species with CoCrMo Metallic Biomaterial Surfaces

There are many molecules, species and mechanisms that contribute to the overall wear and degradation of biometallic alloys like cobalt-chromium-molybdenum (CoCrMo). Following implantation, orthopaedic alloys are subject to an encompassing inflammatory response that will either lead to foreign body giant cell formation and attachment to the surface or the fibrous tissue encapsulation, forming an inflamed periprosthetic joint. In addition to the inflammatory response, tribocorrosion-based processes of alloy-on-alloy or alloy-on-polymer couples release polymeric wear debris, oxides, hydroxides, and metal ions in response to excessive wear, loading and corrosion. It is hypothesized that these processes, biological and triboelectrochemical, are linked together in a feedback-loop, and there is reason to believe that there exists a common catalyst, reactive oxygen species (ROS), that accelerates the cycle. This dissertation explains how ROS are generated in physiological conditions and how they affect electrochemical properties, under what circumstances ROS are consumed intracellularly, how different cell types respond to ROS-rich conditions, and how ROS interact with solution components native to synovial fluid, with a decisive effort and focus on defining their presence and role in the inflamed joint space. By fluorescently labeling individual ROS like hydroxyl radicals (OH·) and hydrogen peroxide (H2O2), we were able to correlate ROS concentrations against time of applied voltage (-1V vs. Ref) as well as against applied voltage for 2 hours. It was found that there exist thresholds for both the production and consumption of ROS, and there is a voltage range for which ROS are produced in measurable quantities. Under similar electrochemical conditions, different cell types (pre-osteoblast-like MC3T3-E1, monocyte macrophage-like U937) were cultured and exposed to an influx of ROS through cathodic excursions. It was found that cells possess a unique ‘electrochemical zone of viability’ per phenotype with reduced glutathione (GSH) activity, a ROS scavenger molecule produced within inflammatory cells, hypothesized to be the oxidative stress suppressor in the U937 cells. This hypothesis was later confirmed when exposing macrophages (RAW 264.7) to simulated synovial fluid, where it was found that ROS (H2O2) had a significant (p \u3c 0.05) effect on intracellular GSH activity (fluorescent intensity). In addition to influencing cell behavior and response, ROS production and exposure was found to alter electrochemical properties of CoCrMo surfaces. Using nearfield electrochemical impedance spectroscopy (NEIS), CoCrMo retrievals and CoCrMo surfaces damaged by electrocautery and ROS-rich solutions were shown to have significantly (p \u3c 0.05) decreased corrosion resistance (RP) with increased constant phase element capacitance (CPE Q) and open circuit potentials (OCPs), indicating that ROS are major contributors in corrosion susceptibility. By interpreting these observations and results, we were able to demonstrate that ROS are influential in several aspects of the inflammatory reaction to metallic biomaterials. The development of new diagnostics and predictive models centered around ROS can lead to safer practices involving orthopaedic alloys and further support our understanding of an inflamed joint space

Thermal Fusion for Sutureless Closure: Devices, Composition, Methods

As minimally invasive surgical techniques progress, the demand for reliable ligation is 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. While 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 between devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue bond. Further, energy-based techniques (e.g., tissue “fusion” or tissue “welding”) exhibit promise for the closure, repair and functional recovery of soft and connective tissues in the orthopaedic, colorectal and dermal domains. To optimize and progress the use of energy-based tissue fusion, a constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required. While rapid tissue bonding may arise from dehydration and water transport, dipole interactions, covalent crosslinks or the coagulation of cellular proteins, long-term tissue repair requires that the reaction to thermal damage be tailored to accelerate and mimic the onset of biological healing and remodeling. The aim of this work is to supplement the findings of published thermal fusion research by exploring the contributions of primary and secondary tissue constituents to the formation of energy-based fusion bonds. Results of this work and their associated implications to the theory of energy-based surgical adhesion will encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond

Removal of cardiovascular obstructions by spark erosion

Coronary atherosclerosis, leading to coronary artery stenosis, is the main cause for ischemic health disease in the Westem countries. Stenoses manifest themselves by limiting blood supply to the myocardium thus causing complaints. A long history of degenerative atherosclerotic disease of the intimal wall of the coronary vessels has usually preceded these events. Probably because of this long term process the composition of the accumulated obstructive tissue is quite heterogeneous and consists of a variety of cells and extra cellular material like lipid containing macrophages, smooth muscle cells, Illonocytes, collagen. cholesterol crystals and calcium. In addition, fresh or organized thrombi may have been deposited on these plaques. Regression of these lesions may be obtained by lifestyle changes or lipid lowering therapy. The acute invasive removal of such complex lesions, however, cannot be achieved by applying simple mechanical or chemical means

Study of Plasma - Liquid Interactions

Disertační práce se zabývá detailním studiem vlastností různých elektrických výbojů generovaných ve vodných roztocích. Tyto výboje se staly v posledním desetiletí velmi populárním tématem, a to zejména díky mnoha praktickým využitím jako například v biomedicíně, čištění odpadních vod, ekologii nebo nanoinženýrství. Studium je zaměřeno na generaci peroxidu vodíku, jakožto jednu z nejvýznamnějších částic generovaných právě elektrickými výboji v kapalinách. Pro první část této práce byla využita speciální výbojová komora zkonstruovaná na Fakultě chemické Vysokého Učení Technického v Brně. Komora byla rozdělena tenkou diafragmovou přepážkou na dvě poloviny, přičemž uvnitř přepážky se nacházela malá dírka. V každé části komory se nacházela jedna elektroda, a obě dvě části komory byly vyplněny kapalinou. Ze zdroje bylo do kapaliny aplikováno vysokofrekvenční napětí (1 a 2 kHz), které tak vlastně upravovalo roztok chloridu sodného (1.5 l). Bylo zjištěno, že tento druh napětí, v porovnání s DC, nezpůsobuje nežádoucí přehřívání roztoku (počáteční vodivost 100 - 800 S/cm) během jeho úpravy při zachování účinnosti produkce peroxidu. Experimentální aparatura pro druhou část práce byla sestavena na Gentské Univerzitě v Belgii. Stejnosměrný výboj byl generován v bublinách plynů (He, Ar, N2, vzduch) v prostředí vodných roztoků. Byla studována generace peroxidu vodíku a odbourávání organických barviv přítomných ve zkoumaném roztoku. Ke generaci peroxidu vodíku byl použit roztok NaH2PO4 . 2H2O (5 microS/cm, V= 750 ml), ke zkoumání rozkladu barviv byly použity roztoky organických barviv Direct Red 79 (20 mg/l) a Direct Blue 106 (20 mg/l, V= 750 ml). Minimální koncentrace peroxidu vodíku byla naměřena při aplikaci proudu 10 mA, zatímco maximální koncentrace peroxidu vodíku byla zaznamenána při použití proudu 30 mA. Rozklad organických barviv vykazoval stejné vlastnosti. Čím vyšší byla dodávaná energie, tím více barviva se odbouralo. Třetí část práce probíhala ve spolupráci s Queen's University of Belfast, Centrum for Plasma Physics, UK. K realizaci experimentů bylo využito vysokofrekvenčního plazmového skalpelu (Arthrocar). Bylo zjištěno, že hodnota koncentrace peroxidu vodíku dosahovala maxima v roztocích s nepatrným přídavkem alkoholu (0.25 %). Celkem byly studovány čtyři 0.15 M roztoky BaCl2, Na2CO3, KCl a NaCl (V= 20 ml), jejichž počáteční vodivost se pohybovala kolem 13 mS/cm. Z výsledků bylo patrné, že největší rozdíl hodnot pH byl zaznamenán u roztoků s přídavkem ethanolu. V optických emisních spektrech byly identifikovány především radikály OH, které jsou prekurzory peroxidu vodíku. Výsledky ukázaly, že plazma v takovémto roztoku je stále tvořeno, což může být považováno za první krok generace plazmatu v organických sloučeninách. Poslední část práce byla zaměřena na tzv. mikroplazmatický jet v přímém kontaktu s kapalnou fází. Tato experimentální práce byla realizována na pracovišti Nanotechnology & Integrated Bio-Engineering Centre (NIBEC), University of Ulster, UK během studijní stáže. Jako vodivé médium byl použit roztok trihydrátu kyseliny chlorozlatité s různou počáteční vodivostí. Zajímavým zjištěním je fakt, že při tomto druhu měření bylo generováno stabilní plazma i při velmi malém výbojovém proudu (0.05 a 0.2 mA), a tedy i peroxid vodíku vznikal při velmi malé vstupní energii, což může být považováno za velmi dobrý výsledek.This Ph.D. thesis contains a detailed investigation of different electric discharges generated in liquids. These discharges have become a popular topic during the last decade, mainly due to many practical applications for example in biomedicine, waste water treatment, ecology and nanoengineering. The study is focused on hydrogen peroxide generation which is one of the most important particles generated by electric discharges in liquids. A special batch discharge chamber, constructed at the Brno University of Technology, Faculty of Chemistry, Czech Republic, was used for the first experimental part. This discharge chamber is separated by a diaphragm membrane with a pin hole at its centre. A single high voltage electrode is placed in each part of the chamber, which is filled by water solution. High frequency voltage (1 and 2 kHz) was used as a power source to treat a NaCl solution (1.5 l). After evaluation of all results it has been found that this kind of power supply, compared to DC, does not cause any unwanted overheating of the solution (initial conductivity 100 - 800 microS/cm) during its treatment and thus the hydrogen peroxide production efficiency is quite high. The second part of this thesis was done at the Ghent University, Department of Applied Physics, Belgium. Here the DC discharge was created in gas bubbles (He, Ar, N2 or Air) flowing water solutions. NaH2PO4 . 2H2O solution (5 microS/cm, V= 750 ml) was used to hydrogen peroxide production studies, Direct Red 79 (20 mg/l) and Direct Blue 106 (20 mg/l, V= 750 ml) solutions were chosen for the organic dyes destruction study. The minimal concentration of the H2O2 was obtained when 10 mA current was applied, while the maximum concentration was observed at the current 30 mA. It leads to the conclusion that concentration of hydrogen peroxide increases with increasing applied current. The organic decomposition showed the same trend. The higher energy was applied, the more organic dye was destructed. The third part of this thesis took place at the Queen's University of Belfast, Centrum for Plasma Physics, UK using high frequency plasma scalpel (Arthrocare). It was found that the hydrogen peroxide concentration has reached the maximal value in solutions with a small addition of an alcohol (0.25 %). Four different treated liquid 0.15 M water solutions of BaCl2, Na2CO3, KCl and NaCl (V= 20 ml) were used. The initial conductivity of the samples was around 13 mS/cm. From the taken results it was obvious that the biggest difference between pH values was obtained in the solution with the additional of ethanol. The active particles generated by discharge were detected by spectra, mainly OH radicals which are understood as precursors to hydrogen peroxide. The main innovation was study of the influence of additional of organic compound on the plasma process. It was obtained that plasma still can be generated in such solution kind which can be considered as the first step to plasma created in the pure organic liquid medium. The last part of this work looked at atmospheric pressure microplasma jet interaction with the liquid phase and it was carried out at the Nanotechnology & Integrated Bio-Engineering Centre (NIBEC), University of Ulster, UK during host internship. As a liquid medium a gold (III) chloride trihydrate (HAuCl4.3H2O) aqueous solution with different initial conductivity was used. Interestingly, even a very low current (0.05 and 0.2 mA) generates stable plasma and produces hydrogen peroxide which can be understood as a very good result. Here, H2O2 behaviours as an oxidizing agent which converts gold precursors into gold nanoparticles.

Design and Development of Non-Equilibrium Plasmas for the Medical Field

There is great interest in the plasma research community on the potential medical applications of non-equilibrium plasmas, called cold atmospheric plasma (CAP), yet currently no such plasma device is approved by the US Food and Drug Administration (FDA). This dissertation seeks to take a holistic look at five novel plasma systems with potential use in the medical field. These systems are all analyzed from an engineering point of view to characterize the plasma and basic biocompatibility from an electrical and thermal approach. The overall design life-cycle for these devices is also examined, with an emphasis on deciding an approval pathway through the Food and Drug Administration, where the intended use of the device is the driving factor. The first device considered is a nanosecond puling circuit devised for skin electroporation. An electrode is developed to help maximize the electric field applied to a substrate and ensure user safety. Voltage and current traces and optical emission spectroscopy are used to characterize the plasma generated for various substrates, showing the non-equilibrium behavior of the plasma for a wide operating range. The second device considered is an existing FDA-cleared electrosurgical device power supply and hand piece, which has been modified for use as a CAP source. By varying the tube length the plasma can be operated in a non-equilibrium state. The third device is a direct write system for depositing thin films in a controlled pattern. This system consists of a dielectric barrier discharge jet attached to a three-dimensional printer head for spatially controlling the plasma location. Various methods of depositing material are used, including directly onto biological substrates. The final two devices are for improving the strength of additively manufactured parts intended for use in custom printed prosthetics. The first is a nanosecond pulsed discharge onto a printed part, which shows 100% strength improvement from the plasma treatment. The second is a planar dielectric barrier discharge mounted onto the head of a three-dimensional printer, which is able to print parts with the same strength as injection molded parts

Study and development of a novel radio frequency electromedical device for the treatment of peri-implantitis: experimental performance analysis, modelling of the electromagnetic interaction with tissues and in vitro and in vivo evaluation

La peri-implantite (PI) è una grave patologia che interessa tessuti peri-implantari molli e duri. Ad oggi, la prevenzione è l’unico mezzo per contrastarla. Recentemente, è stata sperimentata una terapia basata sulla somministrazione di corrente elettrica a radio frequenza (successo: 81%). Il trattamento è stato simulato numericamente, fornendo le distribuzioni di corrente (EC) e campo elettrico (EF) nei tessuti: l’effetto anti-infiammatorio è attribuibile alla EC, quello di rigenerazione ossea al EF. Sono state considerate le misure di bioimpedenza (BM) per individuare le infiammazioni; numericamente si sono osservati cambiamenti nel modulo di impedenza del 4-20% (secondo diversi parametri), anche più alti sperimentalmente (35% infiammazione, 56% PI). Le BM permettono quindi di identificare il tessuto da trattare. Per la ripetibilità, sono state considerate radici di denti naturali, numericamente e sperimentalmente; l’ordine di grandezza è lo stesso (qualche kΩ), anche se ci sono differenze legate alle condizioni di misura. La variabilità intra-soggetto è il 10% in uno stesso giorno, fino al 26% in giorni diversi; quella inter-soggetto è più alta. La sicurezza elettrica è stata attentamente esaminata e si sono individuate le direttive applicabili (IEC 60601-1, 60601-1-2 and 60601-2-2). Sono stati fatti test in vitro per valutare l’effetto della terapia sulla vitalità cellulare: non c’è un significativo aumento della necrosi (vitalità: 85% test, 94% controlli), l’effetto negativo principale è l’apoptosi. Sono stati numericamente indagati possibili effetti termici: non sono stati individuati riscaldamenti nocivi dei tessuti. Si è progettato un nuovo dispositivo (PeriCare®) per trattare la PI, con parti diagnostica (BM) e terapeutica. Si stanno progettando elettrodi specifici e realizzando il prototipo. Si sta compilando il fascicolo tecnico e pianificando i test di conformità, in vista della certificazione. Il dispositivo medico dovrebbe entrare nel mercato entro l’anno.Peri-implantitis is a severe disease affecting hard and soft peri-implant tissues. At present, prevention is the only means to contrast it. Recently, a therapy based on the administration of radio frequency electric current was experimented (success rate: 81%). The treatment was numerically simulated, providing the electric current (EC) and field (EF) distributions in peri-implant tissues: the anti-inflammatory effect can be associated to EC, the bone regeneration to the EF. Bioimpedance measurements (BM) were investigated to detect inflammation; changes in the measured impedance modulus are equal to 4-20% (depending on different parameters) from numerical results, also more evident experimentally (35% inflammation, 56% peri-implantitis). So, BM could allow to detect the tissue to be treated. To evaluate the repeatability, natural tooth roots were numerically and experimentally measured; the order of magnitude is the same (some kΩ), even if there are differences probably due to the measurement conditions. Intra-subject variability was of 10% in the same day, but up to 26% in different days; inter-subject variability was higher. The electrical safety was accurately taken into account. The applicable directives were individuated (IEC 60601-1, 60601-1-2 and 60601-2-2). In vitro tests were carried out to evaluate the effect of the therapy on cell vitality: there is not a significant increase in necrosis (vitality: 85% tests, 94% controls), the main negative effect is apoptosis. Possible thermal effects were numerically investigated: no dangerous tissue heating was observed. A new device for the peri-implantitis treatment, PeriCare®, was designed, with diagnostic (BM) and therapeutic parts. Proper electrodes are being designed and the prototype is being realized. The technical file is being compiled and the conformity verification tests are being planned towards the certification process. Hopefully, the medical device will be placed into the market within this year

Laser-induced forward transfer (LIFT) of water soluble polyvinyl alcohol (PVA) polymers for use as support material for 3D-printed structures

The additive microfabrication method of laser-induced forward transfer (LIFT) permits the creation of functional microstructures with feature sizes down to below a micrometre [1]. Compared to other additive manufacturing techniques, LIFT can be used to deposit a broad range of materials in a contactless fashion. LIFT features the possibility of building out of plane features, but is currently limited to 2D or 2½D structures [2–4]. That is because printing of 3D structures requires sophisticated printing strategies, such as mechanical support structures and post-processing, as the material to be printed is in the liquid phase. Therefore, we propose the use of water-soluble materials as a support (and sacrificial) material, which can be easily removed after printing, by submerging the printed structure in water, without exposing the sample to more aggressive solvents or sintering treatments. Here, we present studies on LIFT printing of polyvinyl alcohol (PVA) polymer thin films via a picosecond pulsed laser source. Glass carriers are coated with a solution of PVA (donor) and brought into proximity to a receiver substrate (glass, silicon) once dried. Focussing of a laser pulse with a beam radius of 2 µm at the interface of carrier and donor leads to the ejection of a small volume of PVA that is being deposited on a receiver substrate. The effect of laser pulse fluence , donor film thickness and receiver material on the morphology (shape and size) of the deposits are studied. Adhesion of the deposits on the receiver is verified via deposition on various receiver materials and via a tape test. The solubility of PVA after laser irradiation is confirmed via dissolution in de-ionised water. In our study, the feasibility of the concept of printing PVA with the help of LIFT is demonstrated. The transfer process maintains the ability of water solubility of the deposits allowing the use as support material in LIFT printing of complex 3D structures. Future studies will investigate the compatibility (i.e. adhesion) of PVA with relevant donor materials, such as metals and functional polymers. References: [1] A. Piqué and P. Serra (2018) Laser Printing of Functional Materials. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. [2] R. C. Y. Auyeung, H. Kim, A. J. Birnbaum, M. Zalalutdinov, S. A. Mathews, and A. Piqué (2009) Laser decal transfer of freestanding microcantilevers and microbridges, Appl. Phys. A, vol. 97, no. 3, pp. 513–519. [3] C. W. Visser, R. Pohl, C. Sun, G.-W. Römer, B. Huis in ‘t Veld, and D. Lohse (2015) Toward 3D Printing of Pure Metals by Laser-Induced Forward Transfer, Adv. Mater., vol. 27, no. 27, pp. 4087–4092. [4] J. Luo et al. (2017) Printing Functional 3D Microdevices by Laser-Induced Forward Transfer, Small, vol. 13, no. 9, p. 1602553

Current Issues and Recent Advances in Pacemaker Therapy

Patients with implanted pacemakers or defibrillators are frequently encountered in various healthcare settings. As these devices may be responsible for, or contribute to a variety of clinically significant issues, familiarity with their function and potential complications facilitates patient management. This book reviews several clinically relevant issues and recent advances of pacemaker therapy: implantation, device follow-up and management of complications. Innovations and research on the frontiers of this technology are also discussed as they may have wider utilization in the future. The book should provide useful information for clinicians involved in the management of patients with implanted antiarrhythmia devices and researchers working in the field of cardiac implants