Academic literature on the topic 'Bio-prosthesis'

Abstract OBJECTIVES Our goal was to examine post hoc patient satisfaction and the decision-making process of choosing a prosthesis for aortic valve replacement (AVR). METHODS We surveyed 113 patients who were operated on for AVR at 60–70 years of age, including 74 patients with a mechanical valve (MECH) and 39 with a bioprosthesis (BIO). The study focused on quality of life and the decision pathway in relation to prosthesis choice and valve-related complications. Decisional conflict was defined as the post hoc uncertainty perceived by patients regarding their choice of prosthesis. RESULTS The survey was performed at a median of 5.2 (3.2–8.1) years after the AVR. Patients with a biological valve were older (BIO: 68.4 years [66.2–69.4] vs MECH: 63.9 [61.9–66.7]; P < 0.001). Global post hoc satisfaction with prosthesis choice was high in both groups (MECH: 95.9%; BIO: 100%), and 85.1% (MECH) and 92.3% (BIO) of them would repeat their choice. Conflict about their decision was equal (MECH: 30.3%; BIO: 32.6%) for different reasons: MECH patients experienced more anticoagulation-related inconvenience (25.9% vs 0%), fear of bleeding (31.1% vs 0%) and prosthesis noise (26.2% vs 0%), whereas more BIO patients feared prosthesis failure (39.7% vs 17.4%) or reoperation (43.5% vs 18.1%). Active involvement in the decision (odds ratio 0.37, 95% confidence interval 0.16–0.85; P = 0.029) and adequate information about the prosthesis (odds ratio 0.34, 95% confidence interval 0.14–0.86; P = 0.020) decreased the risk of conflict about the decision. CONCLUSIONS Although 30% of the responders showed a decisional conflict related to prosthesis-specific interferences, global patient satisfaction with the prosthesis choice for AVR is excellent. Increasing the patient’s involvement in the prosthesis choice through shared accountability and improved information is recommended to decrease the choice-related uncertainty.

Microelectrodes for pain management, neural prosthesis or assistances have a huge medical demand, such as the application of pain management chip or retinal prosthesis addressed on age-related macular degeneration (AMD) and the retinitis pigmentosa (RP). Due to lifelong implanted in human body and direct adhesion of neural tissues, the electrodes and associated insulation materials should possess an ideal bio-compatibility, including non-cytotoxicity and no safety concern elicited by immune responses. Our goal intended to develop retinal prosthesis, an electrical circuit chip used for assisting neural electrons transmission on retina and ameliorating the retinal disability. Therefore, based on the ISO 10993 guidance for implantable medical devices, the electrode prosthesis with insulation material has to conduct bio-compatibility assessment including cytotoxicity, hemolysis, (skin) irritation and pathological implantation examinations. In this study, we manufactured inter-digitated electrode (IDE) chips mimic the electrode prosthesis through photolithography. The titanium and platinum composites were deposited onto a silicon wafer to prepare an electric circuit to mimic the electrode used in retinal prosthesis manufacture, which further be encapsulated to examine the bio-compatibility in compliance with ISO 10993 and ASTM guidance specifically for implantable medical devices. Parylene-C, polyimide and silicon carbide were selected as materials for electrode encapsulation in comparison. Our data revealed parylene-C coating showed a significant excellence on bio-insulation and bio-compatibility specifically addressed on implantable neuron stimulatory devices and provided an economic procedure to package the electrode prosthesis. Therefore, parylene C encapsulation should serve as a consideration for future application on retinal prosthesis manufacture and examination.

Aim. To compare the outcomes of aortic valve replacement using the xenogenic aortic prosthesis Hancock II and the novel Russian xenogenic pericardial prosthesis MEDINGE-BIO.Material and methods. The study included patients operated on for aortic stenosis in the cardiac surgery department № 1 of the Cardiology Research Institute (Tomsk National Research Medical Center). All patients were divided into two groups. The first group included 54 patients with Hancock II prostheses, the second — 91 patients with MEDINGE-BIO prostheses. Hemodynamic characteristics of heart valves were assessed by echocardiography before surgery and before discharge (on average 10 days after surgery).Results. When comparing hemodynamic parameters before and after surgery, significant differences between the groups were not obtained. The average pressure gradient after surgery using Hancock II and MEDINGE-BIO prosthesis was 21,6±7,9 and 17,9±5,6 mm Hg, respectively (p=0,05).Conclusion. The comparative analysis showed that the novel biological prosthesis MEDINGE-BIO has comparable hemodynamic characteristics with the well-known aortic prosthesis Hancock II.

Lower-limb prosthesis design and manufacturing still rely mostly on the workshop process of trial-and-error using expensive unrecyclable composite materials, resulting in time-consuming, material-wasting, and, ultimately, expensive prostheses. Therefore, we investigated the possibility of utilizing Fused Deposition Modeling 3D-printing technology with inexpensive bio-based and bio-degradable Polylactic Acid (PLA) material for prosthesis socket development and manufacturing. The safety and stability of the proposed 3D-printed PLA socket were analyzed using a recently developed generic transtibial numeric model, with boundary conditions of donning and newly developed realistic gait cycle phases of a heel strike and forefoot loading according to ISO 10328. The material properties of the 3D-printed PLA were determined using uniaxial tensile and compression tests on transverse and longitudinal samples. Numerical simulations with all boundary conditions were performed for the 3D-printed PLA and traditional polystyrene check and definitive composite socket. The results showed that the 3D-printed PLA socket withstands the occurring von-Mises stresses of 5.4 MPa and 10.8 MPa under heel strike and push-off gait conditions, respectively. Furthermore, the maximum deformations observed in the 3D-printed PLA socket of 0.74 mm and 2.66 mm were similar to the check socket deformations of 0.67 mm and 2.52 mm during heel strike and push-off, respectively, hence providing the same stability for the amputees. We have shown that an inexpensive, bio-based, and bio-degradable PLA material can be considered for manufacturing the lower-limb prosthesis, resulting in an environmentally friendly and inexpensive solution.

Background: Recently, the use of surgically implanted aortic bioprostheses has been favoured in younger patients. We aimed to analyse the long-term survival and postoperative MACCE (Major Adverse Cardiovascular and Cerebral Event) rates in patients after isolated aortic valve replacement. Methods: We conducted a single-centre observational retrospective study, including all consecutive patients with isolated aortic valve replacement. 1:1 propensity score matching of the preoperative baseline characteristics was performed. Results: A total of 2172 patients were enrolled in the study. After propensity score matching the study included 428 patients: 214 biological vs. 214 mechanical prostheses, divided into two subgroups: group A < 60 years and group B > 60 years. The mean follow-up time was 7.6 ± 3.9 years. Estimated survival was 97 ± 1.9% and 89 ± 3.4% at 10 years for biological and mechanical prosthesis, respectively in group A (p = 0.06). In group B the survival at 10 years was 79.1 ± 5.8% and 69.8 ± 4.4% for biological and mechanical prosthesis, respectively (p = 0.83). In group A, patients with a bioprosthesis exhibited a tendency for higher cumulative incidence MACCE rates compared to patients with a mechanical prosthesis, p = 0.83 (bio 7.3 ± 5.3% vs. mech 4.6 ± 2.2% at 10 years). In group B, patients with a mechanical prosthesis showed a tendency for higher cumulative incidence MACCE rates compared to patients with bioprosthesis, p = 0.86 (bio 4.3 ± 3.1% vs. mech 9.1 ± 3.1% at 10 years). Conclusions: Long-term survival after surgical aortic valve replacement is similar in patients with a biological and mechanical prosthesis, independent of the patients’ age. Moreover, younger patients (<60 years) with bioprosthesis showed a survival benefit, compared to patients with mechanical prosthesis in this age group.

The control scheme in a myoelectric prosthesis includes a pattern recognition section whose task is to decode an input signal, produce a respective actuation signal and drive the motors in the prosthesis limb towards the completion of the user’s intended gesture motion. The pattern recognition architecture works with a classifier which is typically trained and calibrated offline with a supervised learning framework. This method involves the training of classifiers which form part of the pattern recognition scheme, but also induces additional and often undesired lead time in the prosthesis design phase. In this study, a three-phase identification framework is formulated to design a control architecture capable of self-learning patterns from bio-signal inputs from electromyography (neuromuscular) and electroencephalography (brain wave) biosensors, for a transhumeral amputee case study. The results show that the designed self-learning framework can help reduce lead time in prosthesis control interface customisation, and can also be extended as an adaptive control scheme to minimise the performance degradation of the prosthesis controller.

Variable bandgap conjugated donor–acceptor small molecule thin films show absorption spectra similar to those of human eye's photoreceptors. Photoactive devices interfaced with a bio-electrolyte reveal capacitive photocurrent response making them suitable for future full-colour retinal prosthesis.

Обсяг дипломної роботи становить 73 сторінок, містить 28 ілюстрацій, 20 таблиць. Загалом опрацьовано 59 джерел. Актуальність: Захворювання аортального клапана призводять до серйозних дисфункцій, спричинених зворотним потоком клапана або підвищенням його опору. Наслідком цієї патології є важка серцева недостатність, скорочення тривалості та якість життя. Єдине лікування - хірургічна заміна клапана на штучний протез або пластику аортального клапана. Заміна хворого аортального клапана на штучний протез є ефективним методом профілактики серцевої недостатності, збільшення тривалості та поліпшення якості життя. Мета: Моделювання внутрішньої структурної смуги біопротезу аортального клапана. Завдання: переглянути літературу з анатомії судин та клапанів серця; проаналізувати та виявити проблему; побудувати внутрішню структурну клапанну модель клапана у винахіднику AutoCAD; Аналіз варіантів матеріалів для виготовлення клапанного корпусу показав прийнятні механічні характеристики та біосумісність. Основні результати: переглянуто літературу з суміжних тем; порівняльний аналіз існуючих прототипів штучних клапанів серця; вибір «біологічного нітинолу»; Розроблено 5 стандартних розмірів каркаса для біопротезування аортального клапана.
The volume of the graduation work is 73 pages, contains 28 illustrations, 20 tables. In total 59 sources have been processed. Relevance: Aortic valve diseases lead to its severe dysfunction caused backflow on the valve or increased its resistance. The consequence of this pathology is severe heart failure, reduced duration and quality of life. The only treatment is surgical replacement of the valve with an artificial prosthesis or aortic valve plastic. Replacing of a sick aortic valve with an artificial prosthesis is an effective method of preventing heart failure, increasing duration and improving quality of life. Purpose: Modeling of the inner structural band of the aortic valve bio prosthesis. Tasks: to review literature on anatomy of blood vessels and heart valves; analyze and identify the problem; build inner structural band valve model in AutoCAD inventor; analyze the material options for the manufacture of the valve frame showed acceptable mechanical characteristics and biocompatibility. Main results: literature on related topics has been reviewed; comparative analysis of existing prototypes of artificial heart valves; selection of “biological nitinol”; 5 standard sizes of frame for aortic valve bio prosthesis was designed.

Роботу викладено на 80 сторінках, вона містить 5 розділи, 12 ілюстрацію, 34 таблиць та 24 джерела в переліку посилань. В роботі вивчалися дані зарубіжних і вітчизняних авторів по темам поверхневої електроміографії, біопротезів або екзоскелетів, електродів для електроміографії. Проаналізовано роль електроміографії в сучасному світі і зроблені висновки про можливий майбутній розвиток цієї галузі. Розглянуто особливості конструкції електродів і її вплив на якість реєстрованого сигналу і зручність використання. Аналізуються фактори, що впливають на обробку та аналіз сигналів для біопротезування або управління екзоскелетом. Відображено роль електроміографії в розумінні фундаментальних фізіологічних процесів, а також показані перспективи розвитку електроміографії і пристроїв по біоконтролю. Важливі навички аналізу сигналів і роботи по отриманню більш чистого сигналу з поверхні шкіри, в результаті були внесені деякі пропозиції щодо оптимізації всього процесу прийому сигналу, починаючи з вибору електрода і вибору оптимального середовища обробки.
In this work, the data of foreign and domestic authors on the topics of surface electromyography, bioprosthetics or exoskeleton, electrodes for electromyography were studied. The role of electromyography in the modern world and the conclusions about the possible future development of this sphere were analyzed. The peculiarities of the structure of electrodes and its influence on the quality of the registered signal and ease of use are considered. The factors influencing the processing and analysis of the signal for the management of bioprostheses or exoskeletons are analyzed. The role of electromyography in the understanding of fundamental physiological processes is shown, as well as the prospects of the development of electromyography and devices on bio-control. Significant skills in signal analysis and work on obtaining more pure signal from the surface of the skin were obtained, as a result, some suggestions were made on optimizing the whole process of receiving the signal, from the choice of the electrode to the choice of the optimal medium for processing the received information.

Malgré des progrès indéniables dans la compréhension de la fonction cardiaque et dans l’amélioration des techniques médicales et chirurgicales, l'insuffisance cardiaque ischémique représente toujours une cause majeure de mortalité dans le monde De nouvelles approches thérapeutiques, telles que la médecine régénérative et le génie tissulaire, sont développées pour compenser voire se substituer aux tissus endommagés. Une des tentatives de l’ingénierie tissulaire est de reproduire le plus fidèlement possible le comportement mécanique du tissu à traiter. Dans ce travail de thèse, une approche liant la caractérisation mécanique du tissu cardiaque sain avec sa microstructure a été réalisée. A cet effet et afin d’éviter la dégradation des propriétés du matériau due à son asséchement et/ou à sa dé-vascularisation, un protocole expérimental a été défini permettant d’effectuer les mesures dans un environnement proche de son milieu physiologique. Le tissu cardiaque a été ainsi caractérisé à travers l’estimation des modules d’Young suivant deux directions principales par indentations sphériques. Ces résultats ont confirmé ainsi la nature anisotrope du tissu cardiaque. La recherche des durées limites d’exploitation des échantillons après prélèvement (expérimentation ex-vivo) nous a permis de définir une cinétique de rigidification des tissus pouvant être comparée aux techniques de datation utilisées en médecine légale. Une perspective à ces travaux de thèse est l’élaboration d’un matériau de substitution passif dans le but d’obtenir des membranes dont les propriétés mécaniques sont proches du tissu cardiaque. Sur la base de la caractérisation mécanique du myocarde, une modélisation du comportement mécanique d’une bio-prothèse a été définie. Un premier prototype de membrane a été réalisé et expérimenté sur le petit animal. Ces résultats ont constitué une étape indispensable dans le développement d’une assistance biomécanique dans le cadre d’un projet européen FEDER ASCATIM (2018-2021). Enfin, une première transposition de la méthode développée pour le tissu cardiaque a été proposée pour un matériau biologique dont les caractéristiques mécaniques sont peu connues : l’os cortical
Despite undeniable progress of the heart function understanding and in the improvement of medical and surgical techniques, ischaemic heart failure is still a major cause of death worldwide. New therapeutic approaches, such as regenerative medicine and tissue engineering are being developed to compensate or even replace damaged tissues. One of the attempts of tissue engineering is to reproduce as closely as possible the mechanical behavior of the tissue to be treated. In this thesis work, an approach linking the mechanical characterisation of healthy heart tissue with its microstructure was carried out. To this end and in order to avoid the degradation of the material properties due to its drying out and/or de-vascularisation, an experimental protocol was defined to perform the measurements in a context close to its physiological environment. The cardiac tissue was thus characterised through the estimation of Young's modulus in two main directions by spherical indentation. These results thus confirmed the anisotropic nature of the cardiac tissue. The search for the time limits for using the samples after collection (ex-vivo experimentation) enabled us to define a tissue rigidification kinetics which can be compared to the dating techniques used in forensic medicine. One perspective to this thesis work is the development of a passive substitute material in order to obtain membranes whose mechanical properties are close to those of cardiac tissue. On the basis of the mechanical characterization of the myocardium, a model of the mechanical behavior of a bio-prosthesis has been defined. A first membrane prototype has been produced and tested on small animals. These results were an essential step in the development of biomechanical assistance within the framework of a European ERDF ASCATIM project (2018-2021). Finally, a first transposition of the method developed for cardiac tissue was proposed for a biological material whose mechanical characteristics are unknown: cortical bone

Osteoarthritis (OA) is a highly disabling pathology which is worldwide investigated by the scientific community due to its increasing diffusion. The incidence of this age-related disease is increasing with population ageing and worldwide estimates indicate that 9.6% of men and 18% of women with more than 60 years present OA-related symptoms. Osteoarthritis induces the progressive damage of articular cartilage and subchondral bone and can eventually lead to the complete loss of joint functionality. Nowadays, the management of OA includes non-pharmacological, pharmacological, and surgical treatments. Non pharmacological approaches include exercise, weight loss, and physiotherapy and are used in conjunction with pharmacological treatments. The pharmacological management of OA patients is mainly based on the use of anti-inflammatory drugs for pain control. Hence, the pharmacological approach to OA patients is synptomatic, but not resolutive, since it is not able to alter the progression of the disease. These therapeutical options are not suitable for late stage OA patients, whereby the severe pain and the functional limitations caused by advanced OA degeneration are currently resolved by joint replacement. Due to the low self-repair ability of articular cartilage, untreated cartilage lesions can easily degenerate into OA. Different strategies have been developed to treat promptly chondral lesions, comprising cell-based therapies, such as autologous chondrocyte implantation (ACI). These cell-based therapies have been recently proposed also for the treatment of early OA patients in order to overcome or at least delay the need for a more invasive intervention such as joint replacement. However, major issues associated to the clinical use of autologous articular chondrocytes (ACs) are the limited number of cell harvestable from a small cartilage biopsy and the de-differentiation process occurring during the expansion phase required to achieve a clinically relevant number of cells. Furthermore, advanced age and pathological state of joints negatively affect the chondrogenic potential of ACs, representing important factors to be considered when applying chondrocyte-based therapies in particular categories of patients. In view of a possible use of autologous cell-based therapies for OA patients, we analyzed specific features of ACs as cellular yield, cell doubling rates and the dependence between these parameters and patient-related data in a set of 211 OA patients undergoing total joint replacement (Chapter 3). The patient age was not statistically correlated to the cellular yield, but was negatively correlated with the proliferation rate. No significant correlation was observed between the level of cartilage degeneration (ICRS score) and cellular yield and proliferation rates. However, in samples with the highest degree of cartilage degeneration (ICRS score 4) the cellular yield was lower compared to the other three groups (ICRS scores 1-3). In conclusion, we found that age and degenerative state of cartilage affect some basic parameter of articular chondrocytes and should be considered when evaluating the quality of the cell source to be used in clinical applications. To overcome some of the limitations related to the use of ACs, mesenchymal stem cells (MSCs) present in several tissues, such as bone marrow and fat, have been proposed as cell candidate for cartilage treatment thanks to their demonstrated chondrogenic ability. When developing treatments for knee chondral lesions, infrapatellar fat pad and knee subcutaneous adipose tissue, two fat depots easily accessible during knee surgery, can be considered appealing sources for MSCs harvesting. We performed a donor-matched comparison between infrapatellar fat pad MSCs (IFP-MSCs) and knee subcutaneous adipose tissue stem cells (ASCs) obtained from OA patients undergoing total knee replacement, analyzing their immunophenotype and multi-differentiative ability, with a focus on their osteogenic and chondrogenic potential (Chapter 4). We found that these cell populations share common features at the undifferentiated state, such as immunophenotype and clonogenic potential, but display a specific commitment towards the osteogenic and chondrogenic lineage. Indeed, significantly higher levels of osteogenic markers, as calcified matrix deposition and alkaline phosphatase activity, were found in ASCs, highlighting the superior osteogenic commitment of this cell population in comparison with IFP-MSCs. Conversely, IFP-MSCs differentiated towards the chondrogenic lineage by 3D pellet culture showed greater glycosaminoglycans (GAGs) deposition and higher expression of chondrogenic genes as aggrecan (ACAN) and type II collagen (COL2A1) compared to ASCs pellets, revealing a superior chondrogenic potential. This result was supported by lower expression of hyperthrophic and fibrotic markers, as type X (COL10A1) and type I (COL1A1) collagen, in IFP-MSCs pellets compared to ASCs. The observed dissimilarities indicate that populations of adipose-derived MSCs harvested from different anatomical sites have specific features that suggest their preferential use for specific cell-based applications. In the last decade, the co-culture of ACs and MSCs has gained growing interest to investigate the cross-talk between these cell types and to evaluate the possibility of replacing a fraction of ACs with MSCs, in order to reduce the in vitro expansion phase of ACs and subsequently limit their de-differentiation. Controversial results have been reported on the possibility to generate cartilage-like matrix by co-culturing ACs and MSCs, indicating a prominent role for the origin and de-differentiation state of chondrocytes as determinants of the outcomes. We evaluated whether the co-culture of IFP-MSCs and ASCs with a small fraction of ACs was able to lead to cartilage-like matrix generation and to the expression of chondrogenic markers comparable to ACs (Chapter 5). To better resemble a possible clinical application of this strategy we performed autologous co-cultures combining IFP-MSCs and ASCs with expanded and cryo-preserved donor-matched ACs and we used cells derived from OA patients so as not to neglect the impact of the pathological and de-differentiated state of ACs on the outcome of the co-cultures. Chondrogenic genes SRY (sex determining region Y)-box 9 (SOX9), COL2A1, and ACAN were less expressed in co-cultures compared to ACs mono-cultures. No significant differences were observed for GAGs/DNA in mono-cultures, demonstrating the reduced chondrogenic potential of ACs, probably deriving by both their pathological origin and their de-differentiated state. Total GAGs content in co-cultures did not differ significantly from values predicted as the sum of each cell type contribution corrected for the co-culture ratio, as confirmed by histology. Therefore, a small percentage of expanded and cryopreserved ACs did not lead to IFP-MSCs and ASCs chondro-induction. Our results suggest that chondrogenic potential and origin of chondrocytes play a relevant role in the outcome of co-cultures, indicating the need for further investigations to demonstrate their clinical relevance in the treatment of aged osteoarthritic patients. As aforementioned, chondrogenic differentiation of both ACs and MSCs is usually performed in 3D culture models that partially mimic the 3D environment of cartilagineous matrix such as culture in pellets and in 3D scaffolds. Pellet culture is widely used in the field of cartilage tissue engineering to test and optimize differentiation protocols. These experiments normally require to prepare replicates from a relevant number of donors to investigate different culture conditions. Unfortunately, handling a high number of samples in 3D pellet culture is extremely time consuming and is a major issue in experiments with many different conditions. To overcome these limitations, we exploited low-cost rapid prototyping techniques, such as laser ablation and replica molding, to generate multi-well chips in polydimethylsiloxane (PDMS) for the formation and culture of cell aggregates (Chapter 6). Each PDMS chip allowed the simultaneous culture of several pellets leading to a significant reduction in the time required for pellet seeding and medium refresh operations. Proliferation and metabolic activity were comparable between pellets of ACs cultured in PDMS chips and pellets cultured in polypropylene tubes, whereas type II collagen deposition was increased in pellets cultured in the PDMS chips. The same rapid prototyping approach was applied to generate a patterned scaffold. As a proof of concept, we biofabricated a multi-well implantable constructs using clinically approved fibrin glue. We demonstrated that regions with different cell densities can be generated within the construct and that cells can be distributed in a spatially controlled way. These multi-well implantable scaffolds can be seeded with multiple cell types allowing the precise distribution of different cell populations, thus representing a useful tool to investigate in vitro and in vivo cell interactions in a 3D environment. The introduction of engineered tissue into the clinical practice implies the achievement of high quality and safety standards. The use of automated bioreactor-based manufacturing can significantly increase the reproducibility of the results, being minimally affected by operator variability. Furthermore dynamic culture systems, such as perfusion bioreactors, represent a smart approach to overcome the limitations encountered in the static culture of 3D constructs having clinically relevant dimensions. Indeed, perfusion bioreactors have been shown to increase the homogeneity of cell distribution within the scaffold compared to static cell seeding. Perfusion culture provides a continuous and homogeneous influx of fresh medium throughout the construct, improving the quality and homogeneity of the extracellular matrix. The use of optimized protocols for the expansion and re-differentiation of ACs employing clinically approved growth factors is another key step to achieve a successful outcome and to grant the clinical translability of the results. Thus, in collaboration with the group supervised by Prof. Frédéric Mallein-Gerin (Institut de Biologie et Chimie des Proteines, Lyon, France) we tested the combination of a specific cocktail of clinically approved growth factors with a bi-directional perfusion bioreactor (OPB, Oscillating Perfusion Bioreactor) with the aim of improving cartilage matrix production (Chapter 7). We established a perfusion program including phases of high and low perfusion speeds to alternate sequences of cell stimulation and matrix deposition and we compared collagen sponges seeded and cultured in dynamic conditions with sponges seeded and cultured in standard static conditions. We found that perfusion improved cartilage matrix deposition within the sponges, in comparison with static conditions. More precisely, in the sponges cultured in the bioreactor a cartilaginous matrix rich in type II and type IX collagen and GAGs, with no signs of hypertrophy, was produced. Furthermore, a lower amount of type I collagen was produced in the sponges cultured in dynamic conditions, indicating that perfusion limits the risk of fibrocartilage formation. In conclusions, the dynamic culture by means of a perfusion bioreactor combined with the use of a cocktail of clinically approved growth factors proved to be effective for the generation of engineered cartilagineous grafts, improving the homogeneity and quality of the extracellular matrix generated by articular chondrocytes seeded within collagen sponges. Aged patients with late stage OA involving an extensive erosion of articular cartilage and exposure of the underlying subchondral bone cannot be treated with cell-based therapies or standard surgical approaches aiming at cartilage restoration. In these patients, joint replacement is currently the only clinical option to restore the articular function. The insufficient implant stability is an important determinant in the failure of cementless prostheses, leading to an increase in the risk of implant mobilization and in the number of revision procedures, with major drawbacks for patients and for National Health Systems. With the aim of increasing implant osseointegration, porous metallic materials have been developed and applied to cementless implant technology to maximize bone ingrowth and bone-implant contact. More recently, the enrichment of porous titanium with growth factors has been proposed as a novel strategy to further improve implant osseointegration. We combined a macroporous titanium (Trabecular Titanium™, TT), currently used in the clinical practice, with a biocompatible hydrogel (amidated carboxymethylcellulose, CMCA) able to encapsulate osteoinductive factors and osteoprogenitor cells (Chapter 8). In particular, we chose strontium as osteoinductive factor and bone-marrow derived MSCs (BMSCs) as osteogenic progenitor cells for implant enrichment. We tested different concentrations of SrCl2 to select the optimal concentration to induce BMSCs differentiation. We found that SrCl2 at 5 µg/ml significantly increased calcified matrix deposition, type I collagen (COL1A1) expression and alkaline phosphatase activity, being the most effective concentration among the ones tested. The enrichment of TT with CMCA (TT+CMCA) significantly increased cell retention within the implant, representing an important improvement in view of a future clinical application of the bioactive implant. Furthermore, we found that BMSCs cultured in TT+CMCA in the presence of SrCl2 underwent a more efficient osteogenic differentiation, as demonstrated by higher alkaline phosphatase activity and calcium levels. Based on these in vitro results, we performed an in vivo study to evaluate the performance of the bioactive implant generated combining the macroporous titanium with strontium-enriched CMCA and BMSCs (Chapter 9). To mimic implant-bone interaction, an ectopic model was developed grafting TT implants into decellularized bone seeded with human BMSCs. TT was loaded or not with strontium-enriched CMCA and/or BMSCs and constructs were implanted subcutaneously in athymic mice. Osteodeposition at the bone-implant interface was investigated with fluorescence imaging, micro-CT, scanning electron microscopy (SEM), histology and biomechanical testing at different time points. Micro-CT analysis demonstrated the homogeneity of the engineered bone in all groups, supporting the reproducibility of the ectopic model. Fluorescence imaging, histology, SEM and pull-out mechanical testing showed superior tissue ingrowth in TT implants loaded with both strontium-enriched CMCA and BMSCs. In our model, the synergic action of the bioactive hydrogel and BMSCs increased both bone deposition and TT integration, indicating that the generation of bioactive implants able to promote bone deposition is a promising strategy for the improvement of implant osseointegration. Joint inflammation is an important trait of osteoarthritis, indeed synovitis is observed in various degrees in OA patients, with OA synovium showing a mixed inflammatory infiltrate mainly consisting of macrophages. The central role of macrophages in OA evolution supports the interest in investigating their response to signals typical of OA joints, such as the ones contained in the synovial fluid (SF) of OA patients. In collaboration with the Connective Tissue Cells and Repair group supervised by Prof. Gerjo J.V.M. van Osch (Erasmus MC, Rotterdam, The Netherlands), we investigated the effect of SF from OA patients on the transcriptional expression of anti-inflammatory and pro-inflammatory mediators in monocyte-derived macrophages (Chapter 10). SF from donors without any joint pathology was used as control, and the effect of the different types of SF was tested on non-activated macrophages (M0) and on macrophages activated by IFNγ and TNFα (M1 activation) or IL4 (M2 activation). We found that IL10 and IL1ra were modulated by the treatment with OA SF in M0 and M2 conditions. The effect on IL10 was lost in M1 conditions probably due to the high up-regulation induced by the treatment with IFNγ and TNFα. Our results support the idea that arthritic SF is for macrophages a less pro-inflammatory environment compared to control SF. This may mimic the macrophage situation in the joint, where feedback mechanisms are induced to counteract the ongoing pro-inflammatory processes. Altogether our findings highlight the complexity and multiplicity of factors that should be considered for the development of successful cell based treatments for early and late OA patients. We found that basic features of articular chondrocytes were affected by donors age and cartilage degeneration. We also found that expanded OA ACs did not exert a significant chondroinductive effect on co-cultured MSCs, suggesting that the evaluation of the clinical relevance of this approach in OA patients should strongly consider the impact of the de-differentiation state and pathological origin of ACs. Further investigations in this field are needed to verify whether it is possible to replicate the results obtained using non-expanded healthy ACs to co-cultures using expanded ACs from aged patients affected by osteoarthritis. These investigations may require the optimization of clinically approved protocols for expansion and re-differentiation of OA chondrocytes as well as the implementation of three-dimensional and dynamic culture systems. We demonstrated that low-cost rapid prototyping techniques are a useful tool to develop high-throughput systems for the culture of 3D cell aggregates and to generate patterned scaffolds that allow the controlled spatial disposition of different cell types. We also showed that the use of perfusion bioreactors for the dynamic culture of 3D constructs can improve the quality of the engineered tissue, granting a more homogeneous and efficient distribution of nutrients and cells throughout the construct. In order to overcome the limitations related to the use of ACs, MSCs can be considered as promising alternative cell candidates. Here, the identification of specific subsets of MSCs displaying a peculiar commitment should drive the selection of the most suitable cell source. Indeed, as we demonstrated for IFP-MSCs and ASCs, despite common features, specific populations of MSCs harvested from different anatomical sites have intrinsic features that make them more or less suitable for a specific application. Cell-based therapies aiming at cartilage restoration cannot be currently applied to late stage OA patients. However, in this category of patients cell-based approaches can be developed to face issues that are critical in implant technology, such as poor osseointegration. As we proposed here, osteoprogenitor cells, osteoinductive factors, and macroporous metals can be combined to generate a bioactive implant with improved osseointegration ability. This approach could be used to generate “off-the-shelf” implants pre-loaded with osteoinductive factors that can be seeded with autologous BMSCs with a fully intra-operative approach. Finally, when developing cell-based approaches for OA patients, the inflammatory state of the OA joint cannot be neglected. We found that macrophage transcriptional expression was affected by OA synovial fluid. This suggests that OA environments may also induce alterations in the re-implanted cells and highlights the need for better in vitro models to evaluate the response of cells and engineered tissues to a diseased environment. In conclusion, to develop novel cell-based approaches for the treatment of OA basic and translational studies should take into account multiple factors that may affect the clinical outcome, such as the impaired phenotype of OA chondrocytes, the peculiar commitment of specific populations of MSCs, and the impact of inflammatory environment of OA joints.

Chez l'humain, la perte de fonctions motrices causée par l'absence d'une partie du bras affecte l'autonomie et la capacité à réaliser des tâches du quotidien. Pour rétablir certaines des fonctions perdues, la personne handicapée peut utiliser une prothèse qui remplace la partie absente du bras. Aujourd'hui, les prothèses les plus avancées mesurent l'activité des muscles du moignon pour commander leurs articulations. Cependant, plus le handicap est important, plus nombreuses sont les fonctions motrices à restaurer mais moins nombreux sont les muscles à partir desquels recueillir ces mesures. En vue de surmonter cet obstacle, cette thèse explore comment l'emploi de coordinations motrices, c'est-à-dire de régularités dans les rotations des différentes articulations, peut contribuer au pilotage d'une prothèse de bras. À cette fin, deux plateformes expérimentales intervenant comme substituts à une véritable prothèse sont élaborées~: un bras robotique anthropomorphe à taille humaine, et un bras simulé dans un dispositif de réalité virtuelle. Une première expérience met des participants valides aux commandes de ce bras robotique, piloté de façon à ce que son extrémité reproduise les déplacements de la main du participant. Dans une tâche d'atteinte de cible, elle compare la qualité du pilotage selon que le robot adopte des postures plutôt bio-mimétiques ou biologiquement invraisemblables, pour atteindre avec son extrémité le but défini par le participant. Cette expérience montre que la familiarisation au pilotage du robot est meilleure lorsque ses coordinations articulaires sont proches de celles d'un bras humain. Dans une seconde expérience, des participants valides pilotent un bras virtuel dont l'épaule imite les mouvements de leur propre bras, tandis que ses articulations distales (coude et au-delà) sont commandées artificiellement. Dans une tâche de prise et pose d'objet, elle compare la qualité du pilotage selon que ces articulations distales sont commandées uniquement à partir des rotations de l'épaule réelle, ou en intégrant également des informations contextuelles relatives à la cible à atteindre. Cette expérience révèle que l'inclusion d'informations contextuelles améliore notablement la qualité du pilotage. Dans leur ensemble, ces résultats montrent que les coordinations motrices naturelles sont une source d'informations pertinentes pour le pilotage d'une prothèse de bras et peuvent être employées en combinaison avec d'autres signaux de commande pour enrichir ses capacités motrices. En termes d'applications, ils fournissent des pistes pour la conception de techniques de pilotage exploitant les coordinations motrices naturelles pour piloter plusieurs articulations simultanément
In humans, the loss of motor functions associated with the absence of part of the arm disrupts autonomy and reduces the ability to carry out tasks of daily life. To restore some of the lost functions, a person with the aforementioned upper limb disability can use a prosthesis which replaces the missing part of the arm. To this day, the most advanced prostheses measure the activity of muscles located in the stump to control their joints. However, a higher level of disability implies that the prosthesis must restore more motor functions with fewer available muscles from which command signals can be measured. In order to overcome this obstacle, this thesis explores how motor coordinations extit{i.e.} regularities in the way the different joints are put in motion, can be used to drive an arm prosthesis. With this aim, two experimental platforms were developed to act as substitutes for an actual prosthesis: a human-like robotic arm, and a simulated arm in a virtual reality setup. In a first experiment, this robotic arm is driven by able-bodied participants so that its endpoint reproduces the motion of their own hand. Based on a target-reaching task, this experiment compares how well participants perform with this control scheme in two distinct conditions. These conditions correspond to two different strategies to choose the robot's postures when placing its endpoint on the goal defined by the participant: rather human-like or biologically implausible. The results show that employing joint coordinations close to those of a human arm elicits better familiarization to the robot's control scheme. In a second experiment, able-bodied participants drive a virtual arm whose shoulder mimics the participant's actual shoulder motion while its distal joints (elbow and lower) are artificially controlled. Based on a pick-and-place task, this experiment compares how efficiently participants manage to drive the virtual arm with two distinct control schemes. One controls these distal joints' rotations solely from the actual shoulder's motion whereas the other uses additional information in the form of contextual, target-related data. The results reveal that including this contextual information notably improves the performance achieved during the task. Overall, these results show that natural joint coordinations provide a relevant source of information for the control of an arm prosthesis and can be combined with other types of command signals to further expand its motor functions. Regarding application to real-life prosthesis use, they provide insight for the design of control schemes employing natural motor coordinations to drive multiple joints simultaneously

Introduction: To evaluate the safety and overall improvement by the use of prosthetic methyl methacrylate rib-like reconstruction after the chest wall major resections. Patients and Methods: We evaluated 20 patients, from January 2004 to December 2011, treated at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milano, with primary or metastatic tumors of the chest wall,who underwent surgery with reconstruction by a methacrylate shield shaped prosthesis on a Marlex mesh (CAST)+ /-myo-cutaneous flap. We collected all the clinical population data, the comorbidities , the integrated treatments, the intra and post-operative data (blood, plasma, albumin, transfusions , amount of drained liquids) and complications. Results: The median follow-up time was 3,7 years and the overall survival was 100% at 1 year, 85% at 2 years and 70% at 5 years. The most important complications after this surgery were the post-operative bleeding and proteins loss with need of blood, plasma and albumin transfusions, the flap ischemia or infection. Conclusion: This rigid prosthetic reconstruction is an anatomic and physiologic system, which could represent the evolution, in chest wall surgery, from simple substitution to armonic rimodelling and allows to get the oncological radicality also in maximal resections , such as hemi-thoracectomy.

Le développement de prothèses du membre supérieur est couramment divisé en deux parties : la conception mécatronique de la prothèse et l'interface homme-machine dédiée à la commande. L'objectif de cette thèse est de rapprocher ces deux domaines afin de mieux les assortir. Une première étape concerne l'acquisition et le traitement des signaux de commande. Ainsi, une base de données comprenant des signaux électromyographiques et des coordonnées articulaires mesurées par vision par ordinateur a été réalisée. Un réseau de neurones artificiels réalise ensuite la reconstruction de la position de la main par exploitation des séquences électromyographiques. Une architecture de main sous-actionnée bio-inspirée est alors proposée afin de reproduire la cinématique de la main en garantissant une répartition de l'effort de préhension. Cette nouvelle approche consiste à optimiser l'imitation des synergies de la main liées à la saisie, permettant ainsi une commande plus naturelle pour les utilisateurs de prothèses actives
Research on upper-body prosthetic device is commonly divided in two categories: The prosthesis mechatronic conception and the human-machine interface dedicated to the control. This PhD thesis aims to bring together these two fields of research. The first step deals with control signals. Thus, a database containing electromyographic sequences and vision based joint coordinate measurements was created. Then, an artificial neural network achieves the motion estimation from electromyographic sequences. Accordingly, an under-actuated bio-inspired hand architecture is proposed to copy an organic hand motion while ensuring a grasping force distribution. This innovative approach allows to optimize the synergies imitation and proposes a control more intuitive for active prosthesis users

Проект виконано на кафедрі біотехнічних систем Тернопільського національного технічного університету імені Івана Пулюя
Кваліфікаційну роботу магістра присвячено обґрунтуванню структури системи відбору електроміографічних сигналів з поверхні передпліччя для задачі формування сигналів керування виконавчими елементами протеза кисті руки. Запропоновано структуру поверхневих активних електродів та схемо-технічні рішення виконання кіл попереднього підсилення електроміографічних сигналів.
The master's qualification work is devoted to the substantiation of the structure of the electromyographic signal selection system from the surface of the forearm for the task of forming the control signals of the executive elements of the prosthesis of the hand. The structure of surface active electrodes and circuit-technical solutions for performing circles of pre-amplification of electromyographic signals are proposed.
ЗМІСТ ПЕРЕЛІК УМОВНИХ СКОРОЧЕНЬ 8 9 РОЗДІЛ 1. ЗАДАЧА БІОКЕРОВАНОГО ПРОТЕЗУВАННЯ КИСТІ РУКИ .11 1.1 Задача протезування кисті руки 11 1.2 Загальні принципи протезування … .11 1.3 Класифікація способів протезування. Пасивні протези 12 1.4 Класи активних протезів 13 1.5 Класи активних протезів .14 1.6 Висновки до розділу 1 30 РОЗДІЛ 2. БІОКЕРОВАНЕ ПРОТЕЗУВАННЯ НА ОСНОВІ ЕЛЕКТРОМІОГРАФІЧНИХ СИГНАЛІВ .32 2.1 Організація принципів біопротезування 32 2.2 Генезис електроміографічних сигналів. .32 2.3 Поняття та фізичний зміст рухової одиниці 35 2.4 Аналіз типів конструкцій та особливостей електродів для відбору біосигналів 39 2.5 Задача розроблення конструкції активних електродів для відбору ЕМГ сигналів 45 2.6 Висновки до розділу 2 …..46 РОЗДІЛ 3. РОЗРОБЛЕННЯ КОНСТРУКЦІЇ ЕЛЕКТРОДІВ ДЛЯ ВІДБОРУ ЕЛЕКТРОМІОГРАФІЧНИХ СИГНАЛІВ. .48 3.1 Способи реєстрації ЕМГ сигналів …48 3.2 Обґрунтування конструкції електродів ….49 3.3 Інтеграція попереднього підсилювача в структуру конструкції електрода ...50 3.4 Вибір типу матеріалу для виготовлення електрода …...51 3.5 Висновки до розділу 3 …..53 РОЗДІЛ 4. СХЕМО-ТЕХНІЧНІ РІШЕННЯ ВИКОНАННЯ СИСТЕМИ ВІДБОРУ ЕЛЕКТРОМІОГРАФІЧНИХ СИГНАЛІВ ...54 7 4.1 Обґрунтування структурної схеми системи для відбору ЕМГ сигналів 54 4.2 Аналіз відібраних ЕМГ сигналів в середовищі Matlab .55 4.3 Висновки до розділу 4 …..57 РОЗДІЛ 5. СПЕЦІАЛЬНА ЧАСТИНА 59 5.1 Методика проведення медико-біологічних досліджень .59 5.2 Обґрунтування вибору УДК напряму наукового дослідження… 64 РОЗДІЛ 6. ОБҐРУНТУВАННЯ ЕКОНОМІЧНОЇ ЕФЕКТИВНОСТІ… ..67 6.1 Науково-технічна актуальність науково-дослідної роботи. ..67 6.2 Розрахунок витрат на проведення науково-дослідної роботи… ..68 6.3 Науково-технічна ефективність науково-дослідної роботи……….....73 6.4 Висновки до розділу 6 …..77 РОЗДІЛ 7. ОХОРОНА ПРАЦІ ТА БЕЗПЕКА В НАДЗВИЧАЙНИХ СИТУАЦІЯХ .78 7.1 Охорона праці ...78 7.2 Безпека в надзвичайних ситуаціях ……..79 РОЗДІЛ 8. ЕКОЛОГІЯ … .84 8.1 Актуальність охорони навколишнього середовища.. ...84 8.2 Забруднення, що виникають при виготовленні системи відбору електроміографічних сигналів, і шляхи їх зменшення. …..84 8.3 Електромагнітне забруднення довкілля, викликане роботою системою відбору електроміографічних сигналів 88 ЗАГАЛЬНІ ВИСНОВКИ … .89 Бібліографія 91 ДОДАТКИ 95

After nearly a decade of development, human-implantable sensors for detection of muscle activity have recently been demonstrated in the literature. The implantable sensors are powered and communicate wirelessly through the skin using coupled inductor coils. The focus of the present work has been the development of a new approach to modeling the inductively coupled link by using the finite element method (FEM) to simulate a three-dimensional representation of the coils and surrounding magnetic field. The validity of the simulation is tested by comparison to analytically-developed formulas for self-inductance, ac resistance and mutual inductance of the coils. Determination of these parameters is necessary for calculation of the coupling coefficient between the coils, and to fully define the lumped circuit model of the link. This 3D FEM approach is novel and attractive because it is able to encompass physical geometric parameters and material properties that have been traditionally been a challenge to determine. In particular the contribution of a ferrite-core, and the case of non-symmetrical relative coil positioning can be evaluated.
Graduate

AbstractMicrotia is a congenital deformity of the external ear, with a prevalence rate of approximately 1 in 10,000 live births worldwide. The auricle is a distinguishing feature of the face. Its deformity may have severe psycho-social implications on the affected children, affecting their self-confidence. Current reconstructive techniques for microtia mainly include the auricular prosthesis, implantation of alloplastic or an autologous rib cartilage framework. Alloplastic implant reproduces an excellent shape of the ear with no donor site morbidity, however its bio-integration is questionable and may make them prone for extrusion and infection. Sub-cutaneous implantation of autologous rib cartilage still remains the gold-stand treatment for microtia. However this technique has its surgical morbidities and skill demands, which makes it difficult to master. Translational research in the fields of tissue engineering for generation of bone and cartilage for ear reconstruction are emerging trends.

The Chapter will include a brief note on Amputation, Particularly Lower Limb Amputation (LLA), Levels and Causes of LLA. Importance of Prosthetics for LLA are explained in detail. The types of Prosthesis, Application (Donning & Doffing) of prosthesis are included in this chapter. Diagrammatic representation of the prosthesis are added too. Bio mechanical component is explained in detail within this chapter. The advantages and disadvantages of each and every Lower limb Prosthesis are clearly mentioned. Moreover, the Gait analysis & Training after the application of prosthesis are discussed. The reader will get a complete picture of Prosthetics for Lower limb Amputation by going through this chapter for lower limb prosthesis.

Nowadays, we assist the global extension of reliability optimization problems from the design phase of systems and sub-systems to the design and operational phases, not only of systems and sub-systems, but also of bio functionality design. This chapter investigates the relative performances of particle swarm optimization (PSO) variants when used to find reliability in the total hip prosthesis by finding the maximization of jumping distance (JD) to avoid dislocation and the minimization of system's stability to offer mobility. Statistical analysis of different cases of head diameters of 22, 28, 36, 40 mm has been conducted to survey the convergence and relative performances of the main PSO variants when applied to solve reliability in the total hip prosthesis.

It is essential to evaluate the volume and the size of the residual limb in order to design and implement a high-quality prosthesis, which can ensure optimal patient comfort. There is a wide collection of articles dealing with this issue. The blunt point wears out over time in terms of volume in the sense of growth - edema and in the sense of decrease - atrophy. The assessment of wear and tear over time of the contact surfaces belonging to blunt-prosthesis joint, as well as the tribological implications concerning the durability and damage of the prosthesis are absolutely necessary. The damage occurs in the modification of the tissues' vascularization (nutrition). All of these changes result in imperfect contact between the blunt and prosthesis. There are several methods - more or less different in complexity?- of measuring. We have identified 26 studies in this field: the volume of circulating water, anthropometric measurements, ultrasound, x-rays, laser scanning, MRI, bio-impedance, etc. One of the most widely used method is the commercial software package CAD/CAM (e.g. CAPOD system) for prosthetic sockets (higher cost) but also measurements using traditional tools (meter, tape measure, etc.). A common approximation of the residual limb is the one with trunks of cone and spherical segment with one base (spherical top) for a region of amputation that is close to that of this experimental paperwork. Besides the estimation of the volume, the area of demands (area and perimeter) of the curvilinear polygons are approximated by two methods: by considering a given polygon with the apex designed on the foreground and the area of the 3D points for a curvilinear polygon located on the trunks of cones and/or the apex. The selection of the points is done interactively by pointing with the mouse to the polygon's vertexes on the bitmap image displayed by graphical user interface.