O diabetes mellitus é um transtorno metabólico que leva a uma deficiência na secreção de insulina, na sua ação ou em ambos. O mau controle glicêmico pode acarretar em diversas complicações, entre elas, o pé diabético, que é o responsável pela maior parte de amputações não traumáticas dos membros inferiores e gera um custo muito alto para o tratamento de feridas e de cicatrização das amputações. A tecnologia tem proporcionado a criação de novos métodos de tratamento, como as membranas de hidrogel veiculadoras de fármaco. Com isso o nosso objetivo foi testar a eficiência do hidrogel com papaína no tratamento de úlceras em pés diabéticos. A pesquisa foi realizada no município de Porto Nacional (TO) com todos os pacientes portadores de pé diabéticos que deram entrada no HRPPN de 01 de outubro de 2014 a 31 de outubro de 2015, que se encaixavam dentro dos critérios de inclusão do trabalho e assinaram o TCLE. Para a análise socioeconômica aplicou-se um questionário com perguntas objetivas. Para a aplicação da membrana, as feridas foram lavadas com soro fisiológico a 0,9% e os curativos foram realizados de acordo com o protocolo do hospital e trocados a cada 24 horas. Utilizou-se uma planilha de diagnóstico para realizar o acompanhamento diário das feridas. Dezoito pacientes participaram do estudo, sendo que, 16 deles foram internados devido ao pé diabético e ao DM descompensado. 50% dos pacientes eram do sexo feminino e 50% do masculino, todos com idade entre 29 anos e 80 anos. 22% fazem uso de hipoglicemiante oral e insulina e os outros 78% usam apenas hipoglicemiante oral. 82% têm companheiro ou é casado e a maior parte não possui renda ou recebe até um salário mínimo (61%). Quanto à escolaridade, 28% são analfabetos e 34% não concluíram o ensino médio. 50% dos pacientes são naturais de Porto Nacional e 11% de outros estados. Quanto ao conhecimento que os pacientes tinham das complicações que tem como causa o DM, o pé diabético foi a única citada por todos, as demais complicações eram desconhecidas por muitos; somente um paciente tem ciência de todas as complicações. Dos 18 pacientes, 7 puderam ser tratados com a membrana de hidrogel com papaína, mas como não houve melhora significativa, a membrana teve que ser substituída pelo curativo convencional. A membrana não aderiu à pele saudável e nem na ferida, uma vez que apresentou rigidez, fato que pode ter retardado o processo de cicatrização, já que o curativo não envolveu a ferida completamente. A membrana também apresentou baixa taxa de absorção do exsudato, fazendo com que as feridas ficassem maceradas. A cisteína, composto presente na membrana, fez com que ela liberasse um forte odor que causou repulsa nos pacientes e seus familiares, fato que desmotivou o paciente a querer realizar o tratamento. Dados estes resultados, infere-se que a utilização do hidrogel com papaína não trouxe melhora para as feridas do pé diabético, houve um leve desbridamento em algumas feridas, mas sem cicatrização. / Diabetes mellitus is a metabolic disorder that leads to a deficiency in insulin secretion, its action or both. Poor glycemic control can lead to a number of complications, including diabetic foot, which is responsible for most non- traumatic lower limb amputations and generates a very high cost for wound healing and amputation healing. The technology has provided the creation of new treatment methods, such as drug-bearing hydrogel membranes. Our aim is to test the efficiency of papain hydrogel in the treatment of diabetic foot ulcers. The study was carried out in the municipality of Porto Nacional (TO) with all patients with diabetic foot who entered the HRPPN from October 1, 2014 to October 31, 2015, who fit within the inclusion criteria of the work and signed The TCLE. For the socioeconomic analysis a questionnaire with direct questions was applied. For the application of the membrane the wounds were washed with 0.9% saline and the dressings were performed according to the hospital protocol and changed every 24 hours. A diagnostic worksheet was used to perform the daily follow-up of the wounds. Eighteen patients participated in the study, and 16 of them were hospitalized due to diabetic foot and decompensated DM. 50% of the patients were female and 50% were male, all aged between 29 years and 80 years. 22% use oral hypoglycemic and insulin and the other 78% only use oral hypoglycemic. 82% have a partner or are married and most of them have no income or receive up to a minimum wage (61%). As for schooling, 28% are illiterate and 34% did not finish high school. 50% of the patients are from Porto Nacional and 11% from other states. As for the patients\' knowledge of the complications caused by DM, the diabetic foot was the only one mentioned by all, the other complications were unknown by many; only one patient is aware of all the complications. From 18 patients, 7 could be treated with the papain hydrogel membrane, but as there was no significant improvement, the membrane had to be replaced by the conventional dressing. The membrane did not adhere to healthy skin or even to the wound, since it presented rigidity, a fact that may have delayed the healing process since the dressing did not involve the wound completely. The membrane also had a low absorption rate of the exudate, causing the wounds to become macerated. The cysteine, a compound present in the membrane, caused it to release a strong odor that caused disgust in patients and their families, a fact that discouraged the patient from wanting to perform the treatment. Given these results, it was inferred that the use of the papain hydrogel did not improve the wounds of the diabetic foot, there was a slight debridement in some wounds, but without healing.

abstract: BioMEMS has the potential to provide many future tools for life sciences, combined with microfabrication technologies and biomaterials. Especially due to the recent corona 19 epidemic, interest in BioMEMS technology has increased significantly, and the related research has also grown significantly. The field with the highest demand for BioMEMS devices is in the medical field. In particular, the implantable device field is the largest sector where cutting-edge BioMEMS technology is applied along with nanotechnology, artificial intelligence, genetic engineering, etc. However, implantable devices used for brain diseases are still very limited because unlike other parts of human organs, the brain is still unknow area which cannot be completely replaceable.To date, the most commercially used, almost only, implantable device for the brain is a shunt system for the treatment of hydrocephalus. The current cerebrospinal fluid (CSF) shunt treatment yields high failure rates: ~40% within first 2 years and 98% within 10 years. These failures lead to high hospital admission rates and repeated invasive surgical procedures, along with reduced quality of life. New treatments are needed to improve the disease burden associated with hydrocephalus. In this research, the proposed catheter-free, completely-passive miniaturized valve is designed to alleviate hydrocephalus at the originating site of the disorder and diminish failure mechanisms associated with current treatment methods. The valve is composed of hydrogel diaphragm structure and polymer or glass outer frame which are 100% bio-compatible material. The valve aims to be implanted between the sub-arachnoid space and the superior sagittal sinus to regulate the CSF flow substituting for the obstructed arachnoid granulations. A cardiac pacemaker is one of the longest and most widely used implantable devices and the wireless technology is the most widely used with it for easy acquisition of vital signs and rapid disease diagnosis without clinical surgery. But the conventional pacemakers with some wireless technology face some essential complications associated with finite battery life, ultra-vein pacing leads, and risk of infection from device pockets and leads. To solve these problems, wireless cardiac pacemaker operating in fully-passive modality is proposed and demonstrates the promising potential by realizing a prototype and functional evaluating. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2020

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21997号 / 医博第4511号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 妹尾 浩, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23231号 / 工博第4875号 / 新制||工||1761(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 浜地 格, 教授 松田 建児, 教授 生越 友樹 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

The presented diploma thesis deals with a targeted modification of the structural properties of hydrogels, which is closely related to the application properties of these materials (eg transport). Due to the desired pharmacological applications of the use of these materials for targeted drug release, hydrogels based on chitosan and polyvinyl alcohol as substances with good biocompatibility were selected for the study. The combination of these polymers ensured swelling (controlled by the presence of chitosan) and viscoelastic (influenced by the presence of polyvinyl alcohol) properties, which were characterized by a wide range of analytical and physicochemical methods (swelling, tensile strength, rheology, atomic force microscopy or specific surface area, etc.). Information on structural properties played a crucial role not only for a detailed description of the studied materials in terms of whether the structural properties can be changed in a targeted manner, but also served as an explanation for the different release of the active substance diclofenac from the hydrogel matrix. With regard to the literature search, the effect of pH and crosslinking was chosen to modify the properties. From the measured results it was found that even a slight change in pH has an effect on the transport or release of the active substance. The results obtained in this work may be useful in the formation of hydrogel matrices with drugs depending on the intended medical applications.

This thesis pursues monitoring of pH changes and description of properties in phase–separated hydrogels prepared by interaction of polyelectrolyte and oppositely charged surfactants. For the purposes of this work, all hydrogels were prepared by the interaction of hyaluronan with Septonex. All hydrogels were exposed to pH changes (4–9). Changes in pH were being monitored using spectroscopic indicators, methyl orange, methyl red, bromothymol blue and phenolphtalein. The pre– and post– pH changes in properties were compared using rheological methods. Additional information was gathered through thermogravimetric analysis. By these methods it was proved that the changes in the pH can modify the mechanical properties and partly the internal structure of the hydrogels. Rheological tests show, that from the application point of view, the most interesting hydrogels are observed at pH 9 which have the strongest bonds but have low permeability and hydrogels described at pH 7 which are much softer and are capable of absorbing large amounts of water.

The new forms of superabsorbent polymers (SAP) on the base of acrylic acid were developed and studied in this thesis. The SAP are focused on agricultural and environmental applications. While they are applied to the soil, SAP can prevent water losing and they become a reservoir of humidity in case of dry season, moreover in combination with fertiliser they play role of controlled release medium. Eight various samples of SAP were experimentally prepared by networking of partially neutralized acrylic acid. Potassium peroxydisulfate was used as the initiator and N,N–methylenebisacrylamide as the crossing agent. Some of samples contained addition of second monomer of acrylamide. All of them were enriched by fertilisers – natural lignohumate or synthetic NPK or combination of both. The swelling characteristics of prepared samples were investigated in conditions of various ionic strength. The influence of xerogels’ particles size on swelling properties was also observed. The viscoelastic characteristics of hydrogel form of all SAP were determined by using of rotation rheometer. The changing of viscoelastic properties were studied in dependence on time, on freezing and on repeating swelling cycles. On top of that the controlled releasing ability of SAP was tested due to three modelling experiments. The biological activity of all polymer products was tested at the end of the thesis. All samples of SAP were incorporated into the artificial soil and the ability of the water retention in the soil was observed. The growing experiments were running by using of corn plants. The size and the mass of each plant were measured and branching of the root was objectively evaluated by programme Harmonic and Fractal Image Analyzer.

Tissue regeneration using in-vitro scaffold becomes a vital mean to mimic the in-vivo counterpart due to the insufficiency of animal models to predict the applicability of drug and other physiological behavior. Three-dimensional (3D) bio-printing is an emerging technology to reproduce living tissue through controlled allocation of biomaterial and cell. Due to its bio-compatibility, natural hydrogels are commonly considered as the scaffold material in bio-printing process. However, repeatable scaffold structure with good printability and shape fidelity is a challenge with hydrogel material due to weak bonding in polymer chain. Additionally, there are intrinsic limitations for bio-printing of hydrogels due to limited cell proliferation and colonization while cells are immobilized within hydrogels and don’t spread, stretch and migrate to generate new tissue. The goal of this research is to develop a bio-ink suitable for extrusion-based bio-printing process to construct 3D scaffold. In this research, a novel hybrid hydrogel, is designed and systematic quantitative characterization are conducted to validate its printability, shape fidelity and cell viability. The outcomes are measured and quantified which demonstrate the favorable printability and shape fidelity of our proposed material. The research focuses on factors associated with pre-printing, printing and post-printing behavior of bio-ink and their biology. With the proposed hybrid hydrogel, 2 cm tall acellular 3D scaffold is fabricated with proper shape fidelity. Cell viability of the proposed material are tested with multiple cell lines i.e. BxPC3, prostate stem cancer cell, HEK 293, and Porc1 cell and about 90% viability after 15-day incubation have been achieved. The designed hybrid hydrogel demonstrate excellent behavior as bio-ink for bio-printing process which can reproduce scaffold with proper printability, shape fidelity and higher cell survivability. Additionally, the outlined characterization techniques proposed here open-up a novel avenue for quantifiable bio-ink assessment framework in lieu of their qualitative evaluation.

Alginate is a widely used biomaterial for a variety of biomedical applications ranging from drug delivery to cell transplantation. The unique polysaccharide backbone endows the material with a number of useful properties such as hydrophilicity, biocompatibility, and gelation ability. Despite these advantages, one limitation for alginate is the lack of a tunable degradation rate, and its gels may only partially degrade and implants are not fully cleared from the body long after their purpose is fulfilled. To further extend the utility of this biomaterial, we hypothesized that by creating a polymer chimera between polylactic acid (PLA) and alginate we can integrate tunable degradation properties into alginate hydrogels. The alginate-b-PLA diblock copolymers were synthesized by utilizing an inverse electron demand Diels-Alder reaction, and were then fabricated into hydrogels using two approaches: doping with low viscosity alginate (LWA) and direct gelation. These hydrogel chimeras exhibited degradation rates that could be tuned from days to weeks. Morphologically, the combination of different domain sizes of alginate and PLA contributed to different microstructures within the hydrogel matrix that contributes to its degradability. Drug release was not impacted by matrix degradation rate, as four different encapsulated payloads of variable hydrophobicity and molecular weight were encapsulated with the chimeric hydrogels showed comparable release rates to non-degradable alginates. These new degradable alginates could have future utility as degradable drug-eluting implants. / 2022-09-24T00:00:00Z

Táto práca si dáva za cieľ chemicky zasieťovať biodegradovateľný makromonomér ,-itaconyl-PLGA–PEG–PLGA vo vodnom roztoku pri teplote okolia a pri teplote tela (37 °C). ,-itaconyl-PLGA–PEG–PLGA makromonomér môže vo vode vytvárať fyzikálnu sieť vďaka hydrofóbnym interakciám medzi hydrofóbnym PLGA a hydrofilným PEG. Vďaka dvojitej väzbe kyseliny itakonovej, ktorá je k makromonoméru pripojená na jeho koncoch, sa naskytuje možnosť dodatočného chemického zasieťovania fotopolymerizáciou. Výsledkom je hybridná sieť, ktorá zvyšuje mechanickú stabilitu a životnosť hydrogélu. Na priame sledovanie formovania siete prostredníctvom zmeny mechanických vlastností bola v práci použitá fotoreológia.