83 research outputs found
Review and proposition for model-based multivariable-multiobjective optimisation of extrusion-based bioprinting
Consequent to the development of bioprinting technologies for biomedical applications, especially in tissue engineering, a comprehensive review of extrusion-based bioprinting (EBB) has been written. The review was executed in a manner that laid a foundation for effective optimisation strategies to improve the print resolution or shape fidelity and cell viability of EBB through bioink. However, before achieving this aim the shearing characteristic of the bioink (i.e., shear-thinning or thickening) was described by the Ostwald-de Waele and Herschel-Bulkley models, among other reported models. The dependence of bioink shearing characteristics on temperature and time was also discussed. Emphasis on how these dependencies can be influenced by crosslinking of bioink molecules was further highlighted, which can be covalent (chemical-, photo-cross-linking, etc.) or noncovalent (physical cross-linking, host-guest inclusion, ionic interaction, etc.). Models from literature that can physically describe print resolution and cell viability in EBB were discussed and compared. Therefore, multivariable-multiobjective optimisation strategies were proposed with these models.Univerzita Tomáše Bati ve Zlíně, (CZ.02.2.69/0.0/0.0/19_073/0016941)Tomas Bata University, Zlin, Czech Republic [CZ.02.2.69/0.0/0.0/19_073/0016941
Development and Validation of Mechatronic Systems for Image-Guided Needle Interventions and Point-of-Care Breast Cancer Screening with Ultrasound (2D and 3D) and Positron Emission Mammography
The successful intervention of breast cancer relies on effective early detection and definitive diagnosis. While conventional screening mammography has substantially reduced breast cancer-related mortalities, substantial challenges persist in women with dense breasts. Additionally, complex interrelated risk factors and healthcare disparities contribute to breast cancer-related inequities, which restrict accessibility, impose cost constraints, and reduce inclusivity to high-quality healthcare. These limitations predominantly stem from the inadequate sensitivity and clinical utility of currently available approaches in increased-risk populations, including those with dense breasts, underserved and vulnerable populations.
This PhD dissertation aims to describe the development and validation of alternative, cost-effective, robust, and high-resolution systems for point-of-care (POC) breast cancer screening and image-guided needle interventions. Specifically, 2D and 3D ultrasound (US) and positron emission mammography (PEM) were employed to improve detection, independent of breast density, in conjunction with mechatronic and automated approaches for accurate image acquisition and precise interventional workflow. First, a mechatronic guidance system for US-guided biopsy under high-resolution PEM localization was developed to improve spatial sampling of early-stage breast cancers. Validation and phantom studies showed accurate needle positioning and 3D spatial sampling under simulated PEM localization. Subsequently, a whole-breast spatially-tracked 3DUS system for point-of-care screening was developed, optimized, and validated within a clinically-relevant workspace and healthy volunteer studies. To improve robust image acquisition and adaptability to diverse patient populations, an alternative, cost-effective, portable, and patient-dedicated 3D automated breast (AB) US system for point-of-care screening was developed. Validation showed accurate geometric reconstruction, feasible clinical workflow, and proof-of-concept utility across healthy volunteers and acquisition conditions. Lastly, an orthogonal acquisition and 3D complementary breast (CB) US generation approach were described and experimentally validated to improve spatial resolution uniformity by recovering poor out-of-plane resolution. These systems developed and described throughout this dissertation show promise as alternative, cost-effective, robust, and high-resolution approaches for improving early detection and definitive diagnosis. Consequently, these contributions may advance breast cancer-related equities and improve outcomes in increased-risk populations and limited-resource settings
Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents one of the most significant global health issues, given its high prevalence and the challenging nature and physiology of the liver and hepatic surgery, in its many forms. This means that the most appropriate management for HCC should incorporate a multidisciplinary approach, combining the expertise from several different specialties. This book showcases the various steps in the development, diagnosis, staging, and management of HCC and provides views and thoughts from true experts in the field. As such, it is a useful resource for any physician or surgeon, whether training or practicing, who is interested in caring for patients with HCC
Optimization of computer-assisted intraoperative guidance for complex oncological procedures
Mención Internacional en el título de doctorThe role of technology inside the operating room is constantly increasing, allowing surgical procedures previously considered impossible or too risky due to their complexity or limited access. These reliable tools have improved surgical efficiency and safety. Cancer treatment is one of the surgical specialties that has benefited most from these techniques due to its high incidence and the accuracy required for tumor resections with conservative approaches and clear margins.
However, in many cases, introducing these technologies into surgical scenarios is expensive and entails complex setups that are obtrusive, invasive, and increase the operative time. In this thesis, we proposed convenient, accessible, reliable, and non-invasive solutions for two highly complex regions for tumor resection surgeries: pelvis and head and neck. We explored how the introduction of 3D printing, surgical navigation, and augmented reality in these scenarios provided high intraoperative precision.
First, we presented a less invasive setup for osteotomy guidance in pelvic tumor resections based on small patient-specific instruments (PSIs) fabricated with a desktop 3D printer at a low cost. We evaluated their accuracy in a cadaveric study, following a realistic workflow, and obtained similar results to previous studies with more invasive setups. We also identified the ilium as the region more prone to errors.
Then, we proposed surgical navigation using these small PSIs for image-to-patient registration. Artificial landmarks included in the PSIs substitute the anatomical landmarks and the bone surface commonly used for this step, which require additional bone exposure and is, therefore, more invasive. We also presented an alternative and more convenient installation of the dynamic reference frame used to track the patient movements in surgical navigation. The reference frame is inserted in a socket included in the PSIs and can be attached and detached without losing precision and simplifying the installation. We validated the setup in a cadaveric study, evaluating the accuracy and finding the optimal PSI configuration in the three most common scenarios for pelvic tumor resection. The results demonstrated high accuracy, where the main source of error was again incorrect placements of PSIs in regular and homogeneous regions such as the ilium.
The main limitation of PSIs is the guidance error resulting from incorrect placements. To overcome this issue, we proposed augmented reality as a tool to guide PSI installation in the patient’s bone. We developed an application for smartphones and HoloLens 2 that displays the correct position intraoperatively. We measured the placement errors in a conventional and a realistic phantom, including a silicone layer to simulate tissue. The results demonstrated a significant reduction of errors with augmented reality compared to freehand placement, ensuring an installation of the PSI close to the target area.
Finally, we proposed three setups for surgical navigation in palate tumor resections, using optical trackers and augmented reality. The tracking tools for the patient and surgical instruments were fabricated with low-cost desktop 3D printers and designed to provide less invasive setups compared to previous solutions. All setups presented similar results with high accuracy when tested in a 3D-printed patient-specific phantom. They were then validated in the real surgical case, and one of the solutions was applied for intraoperative guidance. Postoperative results demonstrated high navigation accuracy, obtaining optimal surgical outcomes. The proposed solution enabled a conservative surgical approach with a less invasive navigation setup.
To conclude, in this thesis we have proposed new setups for intraoperative navigation in two complex surgical scenarios for tumor resection. We analyzed their navigation precision, defining the optimal configurations to ensure accuracy. With this, we have demonstrated that computer-assisted surgery techniques can be integrated into the surgical workflow with accessible and non-invasive setups. These results are a step further towards optimizing the procedures and continue improving surgical outcomes in complex surgical scenarios.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Raúl San José Estépar.- Secretario: Alba González Álvarez.- Vocal: Simon Droui
Advanced Applications of Rapid Prototyping Technology in Modern Engineering
Rapid prototyping (RP) technology has been widely known and appreciated due to its flexible and customized manufacturing capabilities. The widely studied RP techniques include stereolithography apparatus (SLA), selective laser sintering (SLS), three-dimensional printing (3DP), fused deposition modeling (FDM), 3D plotting, solid ground curing (SGC), multiphase jet solidification (MJS), laminated object manufacturing (LOM). Different techniques are associated with different materials and/or processing principles and thus are devoted to specific applications. RP technology has no longer been only for prototype building rather has been extended for real industrial manufacturing solutions. Today, the RP technology has contributed to almost all engineering areas that include mechanical, materials, industrial, aerospace, electrical and most recently biomedical engineering. This book aims to present the advanced development of RP technologies in various engineering areas as the solutions to the real world engineering problems
Biomechanical & Biochemical Contributions Of Matrix Metalloproteinases In Joint Pain: Models, Mechanisms, & Patients
Chronic joint pain is a major healthcare challenge with a staggering socioeconomic burden. Pain from synovial joints is mediated by the innervated joint tissues. Due to its innervation, the collagenous capsular ligament that surrounds the joint encodes nociceptive signals and transmits them for pain perception. Although increases in the matrix metalloproteinases (MMPs) occur in painful synovial joints either from injury or degenerative disorders, whether and how MMPs may be mechanistically involved in joint pain is unknown. Since the interstitial collagenase MMP-1 has many roles in collagen degradation and signal transduction pathways, it may play a role in nociception from the joint capsular ligament, but this has not been evaluated. The studies in this thesis define the biomechanical and biochemical roles of MMP-1 in afferent signaling using complementary approaches in human, rat, and cell culture models to define fibroblast-neuron and collagen-neuron interactions in nociception, with and without tissue loading. MMPs in the innervated capsular tissue from patients with painful temporomandibular joint disorders are characterized and establish a role for both MMP-1, and the gelatinase MMP-9, as positive correlates with pain symptoms. Studies in the rat show that excess intra-articular MMP-1 is sufficient to induce behavioral sensitivity which is paralleled by neuronal dysregulation in both the peripheral and central nervous systems. Moreover, nociception may be initiated by the microscale catabolism of collagen molecules in the capsular ligament and its subsequent effects on the multiscale biomechanical function of ligament tissues in the presence of MMP-1. To better understand those MMP-1-induced pain mechanisms, a novel co-culture model was designed to mimic the multicellular microenvironment of the capsular ligament incorporating both fibroblasts and peripheral neurons. Biomechanical loading and biochemical degradation each increase both MMP-1 expression and that of the nociceptive neurotransmitter substance P, suggesting possible mechanisms leading to increased MMP-1 in painful joints. Furthermore, since studies reveal that fibroblasts mediate the extent of load-induced MMP-1, fibroblast functionality have a substantive role in contributing to and/or mediating effects of MMP-1 on peripheral neurons. Collectively, studies in this thesis provide a foundational schema for MMP-1 as a biomechanical and biochemical regulator in painful joint disorders
Online learning of physics during a pandemic: A report from an academic experience in Italy
The arrival of the Sars-Cov II has opened a new window on teaching physics in academia.
Frontal lectures have left space for online teaching, teachers have been faced with a new way
of spreading knowledge, adapting contents and modalities of their courses. Students have
faced up with a new way of learning physics, which relies on free access to materials and
their informatics knowledge. We decided to investigate how online didactics has influenced
students’ assessments, motivation, and satisfaction in learning physics during the pandemic
in 2020. The research has involved bachelor (n = 53) and master (n = 27) students of
the Physics Department at the University of Cagliari (N = 80, 47 male; 33 female). The
MANOVA supported significant mean differences about gender and university level with
higher values for girls and master students in almost all variables investigated. The path
analysis showed that student-student, student-teacher interaction, and the organization of
the courses significantly influenced satisfaction and motivation in learning physics. The
results of this study can be used to improve the standards of teaching in physics at the
University of Cagliar
Biomimetic bone grafts: from the lab to the clinic
Aplicat embargament des de la data de defensa fins el dia 17/6/2022Bone grafting is a common medical practice in today’s society, being bone the second most transplanted tissue worldwide after blood. Therefore, it represents a field of major interest for both, biomedical research and the biomedical industry. Despite the ability of bone to self-heal, in some scenarios where defects are large or complex, bone grafts are essential for a successfully regeneration. Although autografting is still today the gold standard in terms of biological performance, the limited availability and morbidity associated with this practice drive to search for alternatives. Synthetic grafts arise as a promising option due to their unlimited availability and the possibility to tune their structure and composition for optimal performance.
The present thesis explores biomimetic calcium deficient hydroxyapatite (CDHA), a promising material for synthetic bone grafts, in a translational-oriented perspective. Two product presentations are studied: A more conventional granulated conformation and a 3D printed personalised format.
Chapter 1 offers a brief overview of bone biology, as well as a state of the art of the currently available bone grafting strategies found in the literature. Chapter 2 focuses on the validation of the in vivo performance of CDHA granules compared to the well- established bovine xenograft particulate grafts in a dental indication in miniature swine. It is concluded that both biomaterials meet the requirements for bone grafting, (i.e., biocompatibility, osseointegration, and osteoconduction). Moreover, it is revealed that granule morphology is a key factor to ensure the preservation of the grafted volume. In the following chapters, the focus is moved to the 3D printed personalised CDHA bone grafts. Chapter 3 investigates different approaches to accelerate the consolidation process of the 3D printed grafts in order to make the technology more suitable for industrial applications, and develops a hydrothermal treatment that reduces the reaction time to 30 minutes instead of the 7 days needed in the biomimetic approach. Despite the slight differences in physicochemical properties associated to this approach (e.g., microstructure, crystalline phase, microporosity, specific surface area), the resulting scaffolds support adhesion and proliferation of rat mesenchymal stem cells, suggesting its potential as bone graft substitutes. In Chapter 4 the hydrothermal route introduced in the previous chapter is compared to the long-established biomimetic treatment in terms of the in vivo performance of the 3D-printed scaffolds through orthotopic implantation in rabbit condyle monocortical defects. The samples treated with this new process, in addition to the excellent biocompatibility, osseointegrative and osteoconductive properties characteristic of biomimetic CDHA, exhibit a significantly higher amount of newly formed bone than the biomimetic counterpart. This enhanced performance is attributed to the higher permeability of the microstructure, as demonstrated with a protein adsorption test. Chapter 5 explores a strategy to enhance the degree of concavity and specific surface area of 3D printed structures obtained by microextrusion, by using nozzles with non-circular cross-sections. Besides achieving the intended purpose and characterising the 3D-printed structures, different technical constraints for the printing process associated to the use of non-circular nozzles are identified. In a further step, this developed technology is applied to the fabrication of 3D-printed bone grafts with concave filament surfaces and tested in vivo in a rabbit condyle orthotopic model in Chapter 6. It is found that using strands with star-shaped cross-sections helps to guide bone, enhancing the osteoconductive properties of the scaffolds. Finally, Chapter 7 summarises all the work carried out in this thesis to transfer the 3D printing technology of synthetic bone grafts to the market, turning it into a commercially available product.L'ús d'empelts ossis és cada vegada més freqüent: l'os és el segon teixit més trasplantat del món, després de la sang. Per això, aquesta pràctica atreu un gran interès tant a nivell de recerca com per a la indústria biomèdica. En casos en què els defectes són massa grossos o complexos, l'ús d'empelts ossis és essencial per aconseguir una bona regeneració. Malgrat que els autoempelts segueixen sent el tractament de primera elecció, la seva disponibilitat limitada així com la morbiditat associada fan necessari buscar altres solucions. Els empelts sintètics sorgeixen com una alternativa prometedora, donada la seva àmplia disponibilitat i la possibilitat de modificar-ne l'estructura i la composició per obtenir un rendiment òptim. En aquesta tesi s'estudia la hidroxiapatita biomimètica deficient en calci (CDHA) per a la fabricació d'empelts ossis sintètics, des d'una perspectiva orientada a la recerca translacional. S'estudien dues presentacions diferents del producte: una configuració en forma de grànuls i un format personalitzat obtingut per impressió 3D. El Capítol 1 recull una descripció general de la biologia de l'os, juntament amb l'estat de l'art de les diferents estratègies d'empelts ossis que es poden trobar a la literatura. El Capítol 2 se centra en l'estudi de la resposta in vivo de grànuls de CDHA, en comparació amb el xenoempelt boví amb més reconeixement mèdic, en una indicació dental en porcs en miniatura. L'estudi conclou que ambdós biomaterials compleixen els requisits d'un empelt ossi, i.e., biocompatibilitat, osteointegració i osteoconducció. A més, es demostra que la morfologia dels grànuls és un factor clau per assegurar la preservació del volum empeltat. En el Capítol 3 s'investiguen diferents processos per accelerar la consolidació dels empelts impresos en 3D per tal d'aconseguir una tecnologia més adient per a aplicacions industrials, i es desenvolupa un tractament hidrotèrmic que redueix el temps de reacció dels 7 dies necessaris per mètodes biomimètics a només 30 minuts. Amb el nou tractament s'observen petites diferències en les propietats fisicoquímiques (per exemple, en la microestructura, en la fase cristal·lina, la microporositat o la superfície específica), però els empelts obtinguts permeten l'adhesió i la proliferació de cèl·lules mare de rata, que indica que són una solució viable com a substituts ossis. En el Capítol 4 el procés hidrotèrmic introduït al capítol anterior es compara amb el tractament biomimètic in vivo mitjançant la implantació ortotòpica d'empelts 3D en defectes monocorticals en còndils de conills. Les mostres tractades amb aquest nou procediment, a més de presentar l'excel·lent biocompatibilitat i les propietats osteointegratives i osteoconductives pròpies de la CDHA biomimètica, també mostren una quantitat significativament més gran de teixit ossi neoformat que la seva contrapart. Aquestes diferències s'atribueixen a la major permeabilitat de la microestructura, tal com es demostra en un assaig d'absorció de proteïnes. En el Capítol 5 s'estudia una estratègia per millorar tant el grau de concavitat com la superfície específica d'estructures impreses en 3D obtingudes per microextrusió. Per això, s'utilitzen broquets d'extrusió amb seccions transversals no circulars. A més d'aconseguir-ho i caracteritzar les propietats de les estructures impreses, s'identifiquen un conjunt de restriccions tècniques associades a l'ús de broquets no circulars. En un pas més, aquesta estratègia s'aplica a la fabricació d'empelts ossis amb superfícies de filament còncaves i, en el Capítol 6, s'assaja in vivo en un model ortotòpic de còndil de conill. S'observa que utilitzar filaments amb una secció transversal en forma d'estrella ajuda a guiar l'os i millora les propietats osteoconductives dels empelts. Finalment, el Capítol 7 resumeix la feina duta a terme al llarg de la tesi per transferir la tecnologia d'impressió 3D d'empelts ossis sintètics, convertint-lo en un producte disponible comercialment.Postprint (published version
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