Mechanisms of aortic dissection: From pathological changes to experimental and models
Aortic dissection continues to be responsible for significant morbidity and mortality, although recent advances in medical data assimilation and in experimental and models have improved our understanding of the initiation and progression of the accumulation of blood within the aortic wall. Hence, there remains a pressing necessity for innovative and enhanced models to more accurately characterize the associated pathological changes. Early on, experimental models were employed to uncover mechanisms in aortic dissection, such as hemodynamic changes and alterations in wall microstructure, and to assess the efficacy of medical implants. While experimental models were once the only option available, more recently they are also being used to validate models. Based on an improved understanding of the deteriorated microstructure of the aortic wall, numerous multiscale material models have been proposed in recent decades to study the state of stress in dissected aortas, including the changes associated with damage and failure. Furthermore, when integrated with accessible patient-derived medical data, models prove to be an invaluable tool for identifying correlations between hemodynamics, wall stresses, or thrombus formation in the deteriorated aortic wall. They are also advantageous for model-guided design of medical implants with the aim of evaluating the deployment and migration of implants in patients. Nonetheless, the utility of models depends largely on patient-derived medical data, such as chosen boundary conditions or tissue properties. In this review article, our objective is to provide a thorough summary of medical data elucidating the pathological alterations associated with this disease. Concurrently, we aim to assess experimental models, as well as multiscale material and patient data-informed models, that investigate various aspects of aortic dissection. In conclusion, we present a discourse on future perspectives, encompassing aspects of disease modeling, numerical challenges, and clinical applications, with a particular focus on aortic dissection. The aspiration is to inspire future studies, deepen our comprehension of the disease, and ultimately shape clinical care and treatment decisions.
Recent progress in multifunctional, reconfigurable, integrated liquid metal-based stretchable sensors and standalone systems
Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.
Strategies for Development of Synthetic Heart Valve Tissue Engineering Scaffolds
The current clinical solutions, including mechanical and bioprosthetic valves for valvular heart diseases, are plagued by coagulation, calcification, nondurability, and the inability to grow with patients. The tissue engineering approach attempts to resolve these shortcomings by producing heart valve scaffolds that may deliver patients a life-long solution. Heart valve scaffolds serve as a three-dimensional support structure made of biocompatible materials that provide adequate porosity for cell infiltration, and nutrient and waste transport, sponsor cell adhesion, proliferation, and differentiation, and allow for extracellular matrix production that together contributes to the generation of functional neotissue. The foundation of successful heart valve tissue engineering is replicating native heart valve architecture, mechanics, and cellular attributes through appropriate biomaterials and scaffold designs. This article reviews biomaterials, the fabrication of heart valve scaffolds, and their in-vitro and in-vivo evaluations applied for heart valve tissue engineering.
Improving Biocompatibility for Next Generation of Metallic Implants
The increasing need for joint replacement surgeries, musculoskeletal repairs, and orthodontics worldwide prompts emerging technologies to evolve with healthcare's changing landscape. Metallic orthopaedic materials have a shared application history with the aerospace industry, making them only partly efficient in the biomedical domain. However, suitability of metallic materials in bone tissue replacements and regenerative therapies remains unchallenged due to their superior mechanical properties, eventhough they are not perfectly biocompatible. Therefore, exploring ways to improve biocompatibility is the most critical step toward designing the next generation of metallic biomaterials. This review discusses methods of improving biocompatibility of metals used in biomedical devices using surface modification, bulk modification, and incorporation of biologics. Our investigation spans multiple length scales, from bulk metals to the effect of microporosities, surface nanoarchitecture, and biomolecules such as DNA incorporation for enhanced biological response in metallic materials. We examine recent technologies such as 3D printing in alloy design and storing surface charge on nanoarchitecture surfaces, metal-on-metal, and ceramic-on-metal coatings to present a coherent and comprehensive understanding of the subject. Finally, we consider the advantages and challenges of metallic biomaterials and identify future directions.
Bio-inspired hemocompatible surface modifications for biomedical applications
When blood first encounters the artificial surface of a medical device, a complex series of biochemical reactions is triggered, potentially resulting in clinical complications such as embolism/occlusion, inflammation, or device failure. Preventing thrombus formation on the surface of blood-contacting devices is crucial for maintaining device functionality and patient safety. As the number of patients reliant on blood-contacting devices continues to grow, minimizing the risk associated with these devices is vital towards lowering healthcare-associated morbidity and mortality. The current standard clinical practice primarily requires the systemic administration of anticoagulants such as heparin, which can result in serious complications such as post-operative bleeding and heparin-induced thrombocytopenia (HIT). Due to these complications, the administration of antithrombotic agents remains one of the leading causes of clinical drug-related deaths. To reduce the side effects spurred by systemic anticoagulation, researchers have been inspired by the hemocompatibility exhibited by natural phenomena, and thus have begun developing medical-grade surfaces which aim to exhibit total hemocompatibility via biomimicry. This review paper aims to address different bio-inspired surface modifications that increase hemocompatibility, discuss the limitations of each method, and explore the future direction for hemocompatible surface research.
Damage tolerant design of additively manufactured metallic components subjected to cyclic loading: State of the art and challenges
Undoubtedly, a better understanding and the further development of approaches for damage tolerant component design of AM parts are among the most significant challenges currently facing the use of these new technologies. This article presents a thorough overview of the workshop discussions. It aims to provide a review of the parameters affecting the damage tolerance of parts produced by additive manufacturing (shortly, AM parts) with special emphasis on the process parameters intrinsic to the AM technologies, the resulting defects and the residual stresses. Based on these aspects, basic concepts are reviewed and critically discussed specifically for AM materials: Criteria for damage tolerant component design;Criteria for the determination of fatigue and fracture properties;Strategies for the determination of the fatigue life in dependence of different manufacturing conditions;Methods for the quantitative characterization of microstructure and defects;Methods for the determination of residual stresses;Effect of the defects and the residual stresses on the fatigue life and behaviour. We see that many of the classic concepts need to be expanded in order to fit with the particular microstructure (grain size and shape, crystal texture) and defect distribution (spatial arrangement, size, shape, amount) present in AM (in particular laser powder bed fusion). For instance, 3D characterization of defects becomes essential, since the defect shapes in AM are diverse and impact the fatigue life in a different way than in the case of conventionally produced components. Such new concepts have immediate consequence on the way one should tackle the determination of the fatigue life of AM parts; for instance, since a classification of defects and a quantification of the tolerable shapes and sizes is still missing, a new strategy must be defined, whereby theoretical calculations (e.g. FEM) allow determining the maximum tolerable defect size, and non-destructive testing (NDT) techniques are required to detect whether such defects are indeed present in the component. Such examples show how component design, damage and failure criteria, and characterization (and/or NDT) become for AM parts fully interlinked. We conclude that the homogenization of these fields represents the current challenge for the engineer and the materials scientist.
Modular Fabrication of Intelligent Material-Tissue Interfaces for Bioinspired and Biomimetic Devices
One of the goals of biomaterials science is to reverse engineer aspects of human and nonhuman physiology. Similar to the body's regulatory mechanisms, such devices must transduce changes in the physiological environment or the presence of an external stimulus into a detectable or therapeutic response. This review is a comprehensive evaluation and critical analysis of the design and fabrication of environmentally responsive cell-material constructs for bioinspired machinery and biomimetic devices. In a bottom-up analysis, we begin by reviewing fundamental principles that explain materials' responses to chemical gradients, biomarkers, electromagnetic fields, light, and temperature. Strategies for fabricating highly ordered assemblies of material components at the nano to macro-scales via directed assembly, lithography, 3D printing and 4D printing are also presented. We conclude with an account of contemporary material-tissue interfaces within bioinspired and biomimetic devices for peptide delivery, cancer theranostics, biomonitoring, neuroprosthetics, soft robotics, and biological machines.
Nanomaterials as photothermal therapeutic agents
Curing cancer has been one of the greatest conundrums in the modern medical field. To reduce side-effects associated with the traditional cancer therapy such as radiotherapy and chemotherapy, photothermal therapy (PTT) has been recognized as one of the most promising treatments for cancer over recent years. PTT relies on ablation agents such as nanomaterials with a photothermal effect, for converting light into heat. In this way, elevated temperature could kill cancer cells while avoiding significant side effects on normal cells. This theory works because normal cells have a higher heat tolerance than cancer cells. Thus, nanomaterials with photothermal effects have attracted enormous attention due to their selectivity and non-invasive attributes. This review article summarizes the current status of employing nanomaterials with photothermal effects for anti-cancer treatment. Mechanisms of the photothermal effect and various factors affecting photothermal performance will be discussed. Efficient and selective PTT is believed to play an increasingly prominent role in cancer treatment. Moreover, merging PTT with other methods of cancer therapies is also discussed as a future trend.
Additive manufacturing of biomaterials
Biomaterials are used to engineer functional restoration of different tissues to improve human health and the quality of life. Biomaterials can be natural or synthetic. Additive manufacturing (AM) is a novel materials processing approach to create parts or prototypes layer-by-layer directly from a computer aided design (CAD) file. The combination of additive manufacturing and biomaterials is very promising, especially towards patient specific clinical applications. Challenges of AM technology along with related materials issues need to be realized to make this approach feasible for broader clinical needs. This approach is already making a significant gain towards numerous commercial biomedical devices. In this review, key additive manufacturing methods are first introduced followed by AM of different materials, and finally applications of AM in various treatment options. Realization of critical challenges and technical issues for different AM methods and biomaterial selections based on clinical needs are vital. Multidisciplinary research will be necessary to face those challenges and fully realize the potential of AM in the coming days.
Application of Materials as Medical Devices with Localized Drug Delivery Capabilities for Enhanced Wound Repair
The plentiful assortment of natural and synthetic materials can be leveraged to accommodate diverse wound types, as well as different stages of the healing process. An ideal material is envisioned to promote tissue repair with minimal inconvenience for patients. Traditional materials employed in the clinical setting often invoke secondary complications, such as infection, pain, foreign body reaction, and chronic inflammation. This review surveys the repertoire of surgical sutures, wound dressings, surgical glues, orthopedic fixation devices and bone fillers with drug eluting capabilities. It highlights the various techniques developed to effectively incorporate drugs into the selected material or blend of materials for both soft and hard tissue repair. The mechanical and chemical attributes of the resultant materials are also discussed, along with their biological outcomes and/or . Perspectives and challenges regarding future research endeavors are also delineated for next-generation wound repair materials.
Advantages and Challenges of Relaxor-PbTiO Ferroelectric Crystals for Electroacoustic Transducers- A Review
Relaxor-PbTiO (PT) based ferroelectric crystals with the perovskite structure have been investigated over the last few decades due to their ultrahigh piezoelectric coefficients ( > 1500 pC/N) and electromechanical coupling factors ( > 90%), far outperforming state-of-the-art ferroelectric polycrystalline Pb(Zr,Ti)O ceramics, and are at the forefront of advanced electroacoustic applications. In this review, the performance merits of relaxor-PT crystals in various electroacoustic devices are presented from a piezoelectric material viewpoint. Opportunities come from not only the ultrahigh properties, specifically coupling and piezoelectric coefficients, but through novel vibration modes and crystallographic/domain engineering. Figure of merits (FOMs) of crystals with various compositions and phases were established for various applications, including medical ultrasonic transducers, underwater transducers, acoustic sensors and tweezers. For each device application, recent developments in relaxor-PT ferroelectric crystals were surveyed and compared with state-of-the-art polycrystalline piezoelectrics, with an emphasis on their strong anisotropic features and crystallographic uniqueness, including engineered domain - property relationships. This review starts with an introduction on electroacoustic transducers and the history of piezoelectric materials. The development of the high performance relaxor-PT single crystals, with a focus on their uniqueness in transducer applications, is then discussed. In the third part, various FOMs of piezoelectric materials for a wide range of ultrasound applications, including diagnostic ultrasound, therapeutic ultrasound, underwater acoustic and passive sensors, tactile sensors and acoustic tweezers, are evaluated to provide a thorough understanding of the materials' behavior under operational conditions. Structure-property-performance relationships are then established. Finally, the impacts and challenges of relaxor-PT crystals are summarized to guide on-going and future research in the development of relaxor-PT crystals for the next generation electroacoustic transducers.
Piezoelectric single crystals for ultrasonic transducers in biomedical applications
Piezoelectric single crystals, which have excellent piezoelectric properties, have extensively been employed for various sensors and actuators applications. In this paper, the state-of-art in piezoelectric single crystals for ultrasonic transducer applications is reviewed. Firstly, the basic principles and design considerations of piezoelectric ultrasonic transducers will be addressed. Then, the popular piezoelectric single crystals used for ultrasonic transducer applications, including LiNbO (LN), PMN-PT and PIN-PMN-PT, will be introduced. After describing the preparation and performance of the single crystals, the recent development of both the single-element and array transducers fabricated using the single crystals will be presented. Finally, various biomedical applications including eye imaging, intravascular imaging, blood flow measurement, photoacoustic imaging, and microbeam applications of the single crystal transducers will be discussed.
Relaxor-based ferroelectric single crystals: growth, domain engineering, characterization and applications
In the past decade, domain engineered relaxor-PT ferroelectric single crystals, including (1-)Pb(MgNb)O-PbTiO (PMN-PT), (1-)Pb(ZnNb)O-PbTiO (PZN-PT) and (1--)Pb(InNb)O-Pb(MgNb)O-PbTiO (PIN-PMN-PT), with compositions near the morphotropic phase boundary (MPB) have triggered a revolution in electromechanical devices owing to their giant piezoelectric properties and ultra-high electromechanical coupling factors. Compared to traditional PbZr Ti O (PZT) ceramics, the piezoelectric coefficient is increased by a factor of 5 and the electromechanical coupling factor is increased from < 70% to > 90%. Many emerging rich physical phenomena, such as charged domain walls, multi-phase coexistence, domain pattern symmetries, etc., have posed challenging fundamental questions for scientists. The superior electromechanical properties of these domain engineered single crystals have prompted the design of a new generation electromechanical devices, including sensors, transducers, actuators and other electromechanical devices, with greatly improved performance. It took less than 7 years from the discovery of larger size PMN-PT single crystals to the commercial production of the high-end ultrasonic imaging probe "PureWave". The speed of development is unprecedented, and the research collaboration between academia and industrial engineers on this topic is truly intriguing. It is also exciting to see that these relaxor-PT single crystals are being used to replace traditional PZT piezoceramics in many new fields outside of medical imaging. The new ternary PIN-PMN-PT single crystals, particularly the ones with Mn-doping, have laid a solid foundation for innovations in high power acoustic projectors and ultrasonic motors, hinting another revolution in underwater SONARs and miniature actuation devices. This article intends to provide a comprehensive review on the development of relaxor-PT single crystals, spanning material discovery, crystal growth techniques, domain engineering concept, and full-matrix property characterization all the way to device innovations. It outlines a truly encouraging story in materials science in the modern era. All key references are provided and 30 complete sets of material parameters for different types of relaxor-PT single crystals are listed in the Appendix. It is the intension of this review article to serve as a resource for those who are interested in basic research and practical applications of these relaxor-PT single crystals. In addition, possible mechanisms of giant piezoelectric properties in these domain-engineered relaxor-PT systems will be discussed based on contributions from polarization rotation and charged domain walls.
Electro-spinning/netting: A strategy for the fabrication of three-dimensional polymer nano-fiber/nets
Since 2006, a rapid development has been achieved in a subject area, so called electro-spinning/netting (ESN), which comprises the conventional electrospinning process and a unique electro-netting process. Electro-netting overcomes the bottleneck problem of electrospinning technique and provides a versatile method for generating spider-web-like nano-nets with ultrafine fiber diameter less than 20 nm. Nano-nets, supported by the conventional electrospun nanofibers in the nano-fiber/nets (NFN) membranes, exhibit numerious attractive characteristics such as extremely small diameter, high porosity, and Steiner tree network geometry, which make NFN membranes optimal candidates for many significant applications. The progress made during the last few years in the field of ESN is highlighted in this review, with particular emphasis on results obtained in the author's research units. After a brief description of the development of the electrospinning and ESN techniques, several fundamental properties of NFN nanomaterials are addressed. Subsequently, the used polymers and the state-of-the-art strategies for the controllable fabrication of NFN membranes are highlighted in terms of the ESN process. Additionally, we highlight some potential applications associated with the remarkable features of NFN nanostructure. Our discussion is concluded with some personal perspectives on the future development in which this wonderful technique could be pursued.
Piezoelectric films for high frequency ultrasonic transducers in biomedical applications
Piezoelectric films have recently attracted considerable attention in the development of various sensor and actuator devices such as nonvolatile memories, tunable microwave circuits and ultrasound transducers. In this paper, an overview of the state of art in piezoelectric films for high frequency transducer applications is presented. Firstly, the basic principles of piezoelectric materials and design considerations for ultrasound transducers will be introduced. Following the review, the current status of the piezoelectric films and recent progress in the development of high frequency ultrasonic transducers will be discussed. Then details for preparation and structure of the materials derived from piezoelectric thick film technologies will be described. Both chemical and physical methods are included in the discussion, namely, the sol-gel approach, aerosol technology and hydrothermal method. The electric and piezoelectric properties of the piezoelectric films, which are very important for transducer applications, such as permittivity and electromechanical coupling factor, are also addressed. Finally, the recent developments in the high frequency transducers and arrays with piezoelectric ZnO and PZT thick film using MEMS technology are presented. In addition, current problems and further direction of the piezoelectric films for very high frequency ultrasound application (up to GHz) are also discussed.