Pub Date : 2020-05-22DOI: 10.1088/2516-1091/ab7cc4
Huagui Zhang, R. Whalley, A. Ferreira, K. Dalgarno
To address the low success rate of new drug discovery, there has been significant growth of in vitro physiological micro-models based on human cells. These may be in the form of cell spheroids, organs-on-a-chip, or multi-cellular tissue cultures, and it is expected that the more biomimetic environment they create will be more accurate than standard cell culture in drug screening prior to clinical testing. However, commercial use of complex co-cultures is still limited. This is due to a lack of validation, low throughput rates, and a lack of compatibility with standard assessment techniques. This review paper focusses specifically on the different engineering approaches used to create, mature and analyse these micro-models, with the aim of exploring which approaches have the potential for high throughput. Active and passive pumping and nozzle based dispensing techniques are considered for fluid handling, with transwells, cell patterning, spheroid cultures and microfluidics considered for establishing and maintaining co-cultures, together with conventional analysis techniques (proteomic and genomic approaches, and immunohistochemistry) and novel sensor systems for downstream analysis are considered. It is concluded that (i) throughput is essential for validation as well as exploitation of the models, and (ii) an integrated approach to model re-design for high throughput is key, with the limitations on throughput at each stage considered in order to develop a system which can deliver and analyse at high throughput rates at all stages of the process.
{"title":"High throughput physiological micro-models for in vitro pre-clinical drug testing: a review of engineering systems approaches","authors":"Huagui Zhang, R. Whalley, A. Ferreira, K. Dalgarno","doi":"10.1088/2516-1091/ab7cc4","DOIUrl":"https://doi.org/10.1088/2516-1091/ab7cc4","url":null,"abstract":"To address the low success rate of new drug discovery, there has been significant growth of in vitro physiological micro-models based on human cells. These may be in the form of cell spheroids, organs-on-a-chip, or multi-cellular tissue cultures, and it is expected that the more biomimetic environment they create will be more accurate than standard cell culture in drug screening prior to clinical testing. However, commercial use of complex co-cultures is still limited. This is due to a lack of validation, low throughput rates, and a lack of compatibility with standard assessment techniques. This review paper focusses specifically on the different engineering approaches used to create, mature and analyse these micro-models, with the aim of exploring which approaches have the potential for high throughput. Active and passive pumping and nozzle based dispensing techniques are considered for fluid handling, with transwells, cell patterning, spheroid cultures and microfluidics considered for establishing and maintaining co-cultures, together with conventional analysis techniques (proteomic and genomic approaches, and immunohistochemistry) and novel sensor systems for downstream analysis are considered. It is concluded that (i) throughput is essential for validation as well as exploitation of the models, and (ii) an integrated approach to model re-design for high throughput is key, with the limitations on throughput at each stage considered in order to develop a system which can deliver and analyse at high throughput rates at all stages of the process.","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab7cc4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41418861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01Epub Date: 2020-01-09DOI: 10.1088/2516-1091/ab5637
Guang Yang, Bhushan Mahadik, Ji Young Choi, John P Fisher
Vascularization is among the top challenges that impede the clinical application of engineered tissues. This challenge has spurred tremendous research endeavor, defined as vascular tissue engineering (VTE) in this article, to establish a pre-existing vascular network inside the tissue engineered graft prior to implantation. Ideally, the engineered vasculature can be integrated into the host vasculature via anastomosis to supply nutrient to all cells instantaneously after surgery. Moreover, sufficient vascularization is of great significance in regenerative medicine from many other perspectives. Due to the critical role of vascularization in successful tissue engineering, we aim to provide an up-to-date overview of the fundamentals and VTE strategies in this article, including angiogenic cells, biomaterial/bio-scaffold design and bio-fabrication approaches, along with the reported utility of vascularized tissue complex in regenerative medicine. We will also share our opinion on the future perspective of this field.
{"title":"Vascularization in tissue engineering: fundamentals and state-of-art.","authors":"Guang Yang, Bhushan Mahadik, Ji Young Choi, John P Fisher","doi":"10.1088/2516-1091/ab5637","DOIUrl":"https://doi.org/10.1088/2516-1091/ab5637","url":null,"abstract":"<p><p>Vascularization is among the top challenges that impede the clinical application of engineered tissues. This challenge has spurred tremendous research endeavor, defined as vascular tissue engineering (VTE) in this article, to establish a pre-existing vascular network inside the tissue engineered graft prior to implantation. Ideally, the engineered vasculature can be integrated into the host vasculature via anastomosis to supply nutrient to all cells instantaneously after surgery. Moreover, sufficient vascularization is of great significance in regenerative medicine from many other perspectives. Due to the critical role of vascularization in successful tissue engineering, we aim to provide an up-to-date overview of the fundamentals and VTE strategies in this article, including angiogenic cells, biomaterial/bio-scaffold design and bio-fabrication approaches, along with the reported utility of vascularized tissue complex in regenerative medicine. We will also share our opinion on the future perspective of this field.</p>","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab5637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39221546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01Epub Date: 2020-02-12DOI: 10.1088/2516-1091/ab6c7d
Courtney Y Wang, Jingjie Hu, Rahul A Sheth, Rahmi Oklu
Endovasular embolization treats diseased and malfunctioned vasculature through a minimally invasive approach that significantly benefits patients. Advances in engineering and materials science have contributed to novel generations of embolic materials that addresses challenges existed in clinically used agents. In this review, we discuss the clinically available embolic agents, their formulations and applications. Additionally, we examine materials in development for embolization, and emphasize the challenges during the process of transitioning from basic science to translational applications in this field.
{"title":"Emerging Embolic Agents in Endovascular Embolization: An Overview.","authors":"Courtney Y Wang, Jingjie Hu, Rahul A Sheth, Rahmi Oklu","doi":"10.1088/2516-1091/ab6c7d","DOIUrl":"10.1088/2516-1091/ab6c7d","url":null,"abstract":"Endovasular embolization treats diseased and malfunctioned vasculature through a minimally invasive approach that significantly benefits patients. Advances in engineering and materials science have contributed to novel generations of embolic materials that addresses challenges existed in clinically used agents. In this review, we discuss the clinically available embolic agents, their formulations and applications. Additionally, we examine materials in development for embolization, and emphasize the challenges during the process of transitioning from basic science to translational applications in this field.","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab6c7d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39462441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-04DOI: 10.1088/2516-1091/ab5418
Xing Xia, Jimmy Zhang, Gengxi Lu, Wenjie Lai, Sandeep K. Krishnan, T. Hsiai, Qifa Zhou, Anh H. Nguyen, H. Cao
Atherosclerosis and its thrombotic complications plague developed countries. The rupture of vulnerable atherosclerotic plaques contributes to acute cardiovascular events and sudden cardiac deaths. Historically, coronary angiography has proved an invaluable tool for the detection and treatment of coronary stenoses that may cause myocardial ischemia; however, the method lacks the capacity to provide thorough information about properties of the lesion (i.e. whether it is lipid-rich, fibrotic, or calcified). Recent advances in electronics, biomaterials and microfabrication techniques have enabled novel multimodality catheters for the assessment of atherosclerotic plaques, such as the integration of intravascular ultrasound with photoacoustic microscopy or optical coherence tomography as well as the utilization of stretchable electrodes for electrochemical impedance spectroscopy. These technologies enable the identification of the complexity and composition of potentially unstable plaques as well as investigations of stenosis severity, plaque formation, and remodeling in both humans and studied animal models. However, real-time detection of vulnerable atherosclerotic lesions prepared for clinical trials remains an unmet challenge. In this context, this review highlights existing and newly-emerged intravascular sensors to assess unstable plaques and their compositions. Advantages and limitations, as well as further development and potential clinical applications, will be thoroughly discussed.
{"title":"Intravascular sensors to assess unstable plaques and their compositions: a review","authors":"Xing Xia, Jimmy Zhang, Gengxi Lu, Wenjie Lai, Sandeep K. Krishnan, T. Hsiai, Qifa Zhou, Anh H. Nguyen, H. Cao","doi":"10.1088/2516-1091/ab5418","DOIUrl":"https://doi.org/10.1088/2516-1091/ab5418","url":null,"abstract":"Atherosclerosis and its thrombotic complications plague developed countries. The rupture of vulnerable atherosclerotic plaques contributes to acute cardiovascular events and sudden cardiac deaths. Historically, coronary angiography has proved an invaluable tool for the detection and treatment of coronary stenoses that may cause myocardial ischemia; however, the method lacks the capacity to provide thorough information about properties of the lesion (i.e. whether it is lipid-rich, fibrotic, or calcified). Recent advances in electronics, biomaterials and microfabrication techniques have enabled novel multimodality catheters for the assessment of atherosclerotic plaques, such as the integration of intravascular ultrasound with photoacoustic microscopy or optical coherence tomography as well as the utilization of stretchable electrodes for electrochemical impedance spectroscopy. These technologies enable the identification of the complexity and composition of potentially unstable plaques as well as investigations of stenosis severity, plaque formation, and remodeling in both humans and studied animal models. However, real-time detection of vulnerable atherosclerotic lesions prepared for clinical trials remains an unmet challenge. In this context, this review highlights existing and newly-emerged intravascular sensors to assess unstable plaques and their compositions. Advantages and limitations, as well as further development and potential clinical applications, will be thoroughly discussed.","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab5418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48026164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-16DOI: 10.1088/2516-1091/ab22cc
David F. Williams
At the present time, there is a significant public and political debate about the safety of implantable medical devices. The debate has centered on the biocompatibility of materials that are used in such devices. It has become clear that, whether the concerns expressed about adverse events in patients are actually caused by the devices or just coincidentally arise in these patients, we are usually unable to address and explain the phenomena that are described. This is very damaging to the medical device industry and the relevant clinical disciplines; it is, however, not surprising, since current ideas about the mechanisms of biocompatibility and the development of the host response are well out-of-date and do not take into account knowledge about inflammation, immunity and fibrosis. This perspectives paper discusses this new knowledge and presents the outline of new biocompatibility paradigms, involving mechanotransduction and sterile inflammation. Based on these ideas, totally new procedures for the determination of biological safety are proposed which, if implemented, could improve patient safety and confidence in the performance of implanted devices.
{"title":"Biocompatibility in clinical practice: predictable and unpredictable outcomes","authors":"David F. Williams","doi":"10.1088/2516-1091/ab22cc","DOIUrl":"https://doi.org/10.1088/2516-1091/ab22cc","url":null,"abstract":"At the present time, there is a significant public and political debate about the safety of implantable medical devices. The debate has centered on the biocompatibility of materials that are used in such devices. It has become clear that, whether the concerns expressed about adverse events in patients are actually caused by the devices or just coincidentally arise in these patients, we are usually unable to address and explain the phenomena that are described. This is very damaging to the medical device industry and the relevant clinical disciplines; it is, however, not surprising, since current ideas about the mechanisms of biocompatibility and the development of the host response are well out-of-date and do not take into account knowledge about inflammation, immunity and fibrosis. This perspectives paper discusses this new knowledge and presents the outline of new biocompatibility paradigms, involving mechanotransduction and sterile inflammation. Based on these ideas, totally new procedures for the determination of biological safety are proposed which, if implemented, could improve patient safety and confidence in the performance of implanted devices.","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab22cc","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47755865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-16DOI: 10.1088/2516-1091/ab280b
M. Sitti
Biomedical Engineering new interdisciplinary journal publishing high-quality authoritative reviews and opinion in most significant and exciting areas of biomedical engineering research. current state of the and emerging trends on of
{"title":"Welcome to Progress in Biomedical Engineering","authors":"M. Sitti","doi":"10.1088/2516-1091/ab280b","DOIUrl":"https://doi.org/10.1088/2516-1091/ab280b","url":null,"abstract":"Biomedical Engineering new interdisciplinary journal publishing high-quality authoritative reviews and opinion in most significant and exciting areas of biomedical engineering research. current state of the and emerging trends on of","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab280b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46787166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-16DOI: 10.1088/2516-1091/ab22d5
H. Ceylan, I. Yasa, Ugur Kilic, Wenqi Hu, M. Sitti
Untethered mobile microrobots have the potential to transform medicine radically. Their small size and wireless mobility can enable access to and navigation in confined, small, hard-to-reach, and sensitive inner body sites, where they can provide new ways of minimally invasive interventions and targeted diagnosis and therapy down to the cellular length scales with high precision and repeatability. The exponential recent progress of the field at the preclinical level raises anticipations for their near-future clinical prospects. To pave the way for this transformation to happen, however, the formerly proposed microrobotic system designs need a comprehensive review by including essential aspects that a microrobot needs to function properly and safely in given in vivo conditions of a targeted medical problem. The present review provides a translational perspective on medical microrobotics research with an application-oriented, integrative design approach. The blueprint of a medical microrobot needs to take account of microrobot shape, material composition, manufacturing technique, permeation of biological barriers, deployment strategy, actuation and control methods, medical imaging modality, and the execution of the prescribed medical tasks altogether at the same time. The incorporation of functional information pertaining each such element to the physical design of the microrobot is highly dependent on the specific clinical application scenario. We discuss the complexity of the challenges ahead and the potential directions to overcome them. We also throw light on the potential regulatory aspects of medical microrobots toward their bench-to-bedside translation. Such a multifaceted undertaking entails multidisciplinary involvement of engineers, materials scientists, biologists and medical doctors, and bringing their focus on specific medical problems where microrobots could make a disruptive or radical impact.
{"title":"Translational prospects of untethered medical microrobots","authors":"H. Ceylan, I. Yasa, Ugur Kilic, Wenqi Hu, M. Sitti","doi":"10.1088/2516-1091/ab22d5","DOIUrl":"https://doi.org/10.1088/2516-1091/ab22d5","url":null,"abstract":"Untethered mobile microrobots have the potential to transform medicine radically. Their small size and wireless mobility can enable access to and navigation in confined, small, hard-to-reach, and sensitive inner body sites, where they can provide new ways of minimally invasive interventions and targeted diagnosis and therapy down to the cellular length scales with high precision and repeatability. The exponential recent progress of the field at the preclinical level raises anticipations for their near-future clinical prospects. To pave the way for this transformation to happen, however, the formerly proposed microrobotic system designs need a comprehensive review by including essential aspects that a microrobot needs to function properly and safely in given in vivo conditions of a targeted medical problem. The present review provides a translational perspective on medical microrobotics research with an application-oriented, integrative design approach. The blueprint of a medical microrobot needs to take account of microrobot shape, material composition, manufacturing technique, permeation of biological barriers, deployment strategy, actuation and control methods, medical imaging modality, and the execution of the prescribed medical tasks altogether at the same time. The incorporation of functional information pertaining each such element to the physical design of the microrobot is highly dependent on the specific clinical application scenario. We discuss the complexity of the challenges ahead and the potential directions to overcome them. We also throw light on the potential regulatory aspects of medical microrobots toward their bench-to-bedside translation. Such a multifaceted undertaking entails multidisciplinary involvement of engineers, materials scientists, biologists and medical doctors, and bringing their focus on specific medical problems where microrobots could make a disruptive or radical impact.","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab22d5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44515409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-16DOI: 10.1088/2516-1091/ab23df
Kirsten Fetah, Peyton J. Tebon, M. Goudie, J. Eichenbaum, Li Ren, N. Barros, Rohollah Nasiri, S. Ahadian, N. Ashammakhi, M. Dokmeci, A. Khademhosseini
Understanding complex cell–cell interactions and physiological microenvironments is critical for the development of new therapies for treating human diseases. Current animal models fail to accurately predict success of therapeutic compounds and clinical treatments. Advances in biomaterials, engineering, and additive manufacturing have led to the development of printed tissues, lab-on-chip devices, and, more recently, organ-on-chip systems. These technologies have promising applications for the fabrication of more physiologically representative human tissues and can be used for high-throughput testing of human cells and organoids. These organ-on-chip systems can be fabricated with integrated fluidics to allow for the precise control and manipulation of cellular microenvironments with multiple cell types. Further control over these cellular environments can be achieved with bioprinting, allowing for three-dimensional (3D) printing of multiple materials and cell types to provide precisely controlled structures manufactured in a one-step process. As cell behavior is highly dependent on the physical and chemical properties of the environment, the behavior of cells in two-dimensional and 3D culture systems varies drastically. Providing devices that can support long-term cell culture and controlled stimulation of 3D culture systems will have a profound impact on the study of physiological processes and disease, as well as the development of new therapies. This review highlights recent advances in organ-on-chip systems and 3D bioprinting techniques for the development of in vitro physiological models.
{"title":"The emergence of 3D bioprinting in organ-on-chip systems","authors":"Kirsten Fetah, Peyton J. Tebon, M. Goudie, J. Eichenbaum, Li Ren, N. Barros, Rohollah Nasiri, S. Ahadian, N. Ashammakhi, M. Dokmeci, A. Khademhosseini","doi":"10.1088/2516-1091/ab23df","DOIUrl":"https://doi.org/10.1088/2516-1091/ab23df","url":null,"abstract":"Understanding complex cell–cell interactions and physiological microenvironments is critical for the development of new therapies for treating human diseases. Current animal models fail to accurately predict success of therapeutic compounds and clinical treatments. Advances in biomaterials, engineering, and additive manufacturing have led to the development of printed tissues, lab-on-chip devices, and, more recently, organ-on-chip systems. These technologies have promising applications for the fabrication of more physiologically representative human tissues and can be used for high-throughput testing of human cells and organoids. These organ-on-chip systems can be fabricated with integrated fluidics to allow for the precise control and manipulation of cellular microenvironments with multiple cell types. Further control over these cellular environments can be achieved with bioprinting, allowing for three-dimensional (3D) printing of multiple materials and cell types to provide precisely controlled structures manufactured in a one-step process. As cell behavior is highly dependent on the physical and chemical properties of the environment, the behavior of cells in two-dimensional and 3D culture systems varies drastically. Providing devices that can support long-term cell culture and controlled stimulation of 3D culture systems will have a profound impact on the study of physiological processes and disease, as well as the development of new therapies. This review highlights recent advances in organ-on-chip systems and 3D bioprinting techniques for the development of in vitro physiological models.","PeriodicalId":74582,"journal":{"name":"Progress in biomedical engineering (Bristol, England)","volume":"133 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/2516-1091/ab23df","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41283312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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