Physicochemical Characterization and Biocompatibility of Alginate-Polycation Microcapsules Designed for Islet Transplantation

RÉSUMÉ La microencapsulation représente une stratégie visant à protéger les cellules ou les tissus thérapeutiques du rejet de greffe à l’aide d’une barrière physique. Cette approche est avantageuse puisqu’elle ne nécessite pas l’administration d’immunosuppresseurs à long terme et qu’elle permet l’option d’exploiter des sources de cellules non-cadavériques (ex. les cellules d’animaux). Les microcapsules que nous étudions sont conçues pour l’immunoprotection des îlots de Langerhans (qui sont responsables de sécréter l’insuline) dans le but de traiter le diabète insulino-dépendant. La transplantation d’îlots microencapsulés n’est pas encore utilisée régulièrement en clinique parce que la survie et le fonctionnement des cellules greffées restent limités. Un facteur qui contribue à l’échec de la greffe est la biocompatibilité inadéquate des microcapsules ellesmêmes. Dans ce cas, les cellules immunitaires adhèrent à la surface du dispositif et sécrètent des substances cytotoxiques pouvant pénétrer la barrière protectrice et endommager les cellules à l’intérieur. Ensuite, du tissu fibrotique se développe autour de l’implant, ce qui peut obstruer ou limiter la diffusion des nutriments, de l’oxygène, du glucose et de l’insuline à travers la membrane et ultimement mener au dysfonctionnement et/ou la mort des cellules encapsulées. Au moins deux groupes de recherche ont démontré la faisabilité, sous conditions optimales, de fabriquer des microcapsules d’alginate-polycation biocompatibles. Cependant, la plupart des laboratoires ont de la difficulté à reproduire de tels résultats. Ceci souligne notre manque de connaissances à propos des paramètres importants qui déterminent la biocompatibilité de la microcapsule. Cette situation est fortement reliée au fait qu’aucun standard n’existe pouvant nous guider dans la fabrication des microcapsules afin d’atteindre une biocompatibilité et une bioperformance optimales. A l’aide des techniques d’analyses physicochimiques, cette recherche cherchait à comprendre quelles propriétés de la microcapsule sont importantes pour déterminer sa biocompatibilité. L’objectif de ce travail était d’élucider les corrélations entre la structure chimique, les propriétés physicochimiques, et la biocompatibilité in vivo des microcapsules à base d’alginate. Ces informations aideront la communauté scientifique à comprendre les facteurs----------ABSTRACT Microencapsulation represents a method for immunoprotecting transplanted therapeutic cells or tissues from graft rejection using a physical barrier. This approach is advantageous in that it eliminates the need to induce long-term immunosuppression and allows the option of transplanting non-cadaveric cell sources, such as animal cells and stem cell-derived tissues. The microcapsules that we have investigated are designed to immunoprotect islets of Langerhans (i.e. clusters of insulin-secreting cells), with the goal of treating insulin-dependent diabetes. Microencapsulated islet transplantation has not yet reached regular clinical application because graft survival and function remains limited and variable. One of the main factors that contribute to graft failure is an inadequate biocompatibility of the microcapsule itself. Upon recognition of the microcapsule, host immune cells adhere to the device and secrete cytotoxic substances that are small enough to penetrate the protective barrier and potentially harm the cells within. As the inflammatory response persists, fibrotic tissue develops around the implant and can hinder the diffusion of cell nutrients, oxygen, glucose and insulin into and out of the microcapsule, thereby leading to encapsulated cell dysfunction and death. At least two research groups have demonstrated the feasibility of producing alginatepolycation microcapsules that are biocompatible. However, most labs have had difficulty reproducing such results. This underlines our lack of understanding about the parameters that are important for determining the biocompatibility of the microcapsule. This situation is intimately related to the fact that no standards currently exist to guide the fabrication process of microcapsules in order to achieve optimal biocompatibility and bioperformance. With the aid of techniques for physicochemical analysis, this research focused on understanding which properties of the microcapsule are the most important for determining its biocompatibility. The objective of this work was to elucidate correlations between the chemical make-up, physicochemical properties, and in vivo biocompatibility of alginate-based microcapsules. This information is expected to help the research community understand what factors must be controlled and standardized in order to achieve optimal biocompatibility. Our approach was based on the hypothesis that the immune response to the microcapsules i

Situational Awareness: Examining Factors that Affect Cyber-Risks in the Maritime Sector

Standard risk assessments are used to define and prioritize threats within a sector. However, the rising number of cybersecurity risks in maritime are often temperamental to a range of environmental, technical, and social factors. A change during an incident can significantly alter the risks and, consequently, the incident outcomes. Therefore, agile, changing risk profiles are becoming more necessary in the modern world. In addition to static and dynamic, maritime operational risks can be affected by cyber, cyber-physical, or physical elements. This demonstrates the equal use of information and operational technology (IT/OT); however, most quantitative risk assessment frameworks focus on one or the other. This is not ideal, based on technological trends in the maritime sector. This article explores the factors that affect maritime cyber-risk and examines popular risk frameworks to see whether important maritime-related elements are unaccounted for. These findings are further examined with the results of a survey we conducted to assess the situational awareness of the sector around cyber-risks in maritime. Suggestions for future work on are then made based on our findings

Cyber-SHIP: Developing Next Generation Maritime Cyber Research Capabilities

As a growing global threat, cyber-attacks can cost millions of dollars or endanger national stability and human lives. While relatively well understood in most sectors, it is becoming clear that, although the maritime sector is becoming more digitally advanced (e.g., autonomy), it is not well protected against cyber or cyber-physical attacks and accidents. To help improve sector-wide safety and resiliency, the University of Plymouth (UoP) is creating a specialised maritime-cyber lab, which combines maritime technology and traditional cyber-security labs. This is in response to the lack of research and mitigation capabilities and will create a new resource capability for academia, government, and industry research into maritime cybersecurity risks and threats. These lab capabilities will also enhance existing maritime-cyber capabilities across the world, including risk assessment frameworks, cybersecurity ranges/labs, ship simulators, mariner training programmes, autonomous ships, etc. The goal of this paper is to explain the need for next generation maritime-cyber research capabilities, and demonstrate how something like the proposed Cyber-SHIP Lab (Hardware, Software, Information and Protections) will help industry, government, and academia understand and mitigate cyber threats in the maritime sector. The authors believe a next generation cyber-secure lab should host a range of real, non-simulated, maritime systems. With multiple configurations to mirror existing bridge system set-ups, the technology can be studied for individual system weakness as well as the system-of-systems vulnerabilities. Such as lab would support a range of research that cannot be achieved with simulators alone and help support the next generation of cyber-secure marine systems

A Cyber-Security Review of Emerging Technology in the Maritime Industry

The maritime industry is a complex cornerstone of global transportation infrastructure. To ensure smooth, safe and timely operations, technologies have been created or adapted over time to aid the maritime sector. Agile adaptations are an important part of maintaining safe operational standards despite economic, environmental, and technological changes. As ship-based systems and port infrastructure become more technologically advanced and complex, it is important to understand how emerging technology can both improve, and hinder, maritime operations. One of the main drawbacks of evolving technology is the increase of cyber-security vulnerabilities, as these systems become more complex and inter-connected. Maritime technology has the added complexity of hosting both information technology and operational technology (IT and OT) nearly equally. This paper gives an overview of emerging or growing technologies within maritime, specifically how they work, the benefits they bring, as well as cyber-security concerns to consider when accepting them into regular practice

Extinction Coefficient of Gold Nanostars

Gold nanostars (NStars) are highly attractive for biological applications due to their surface chemistry, facile synthesis, and optical properties. Here, we synthesize NStars in HEPES buffer at different HEPES/Au ratios, producing NStars of different sizes and shapes and therefore varying optical properties. We measure the extinction coefficient of the synthesized NStars at their maximum surface plasmon resonances (SPRs), which range from 5.7 × 10⁸ to 26.8 × 10⁸ M⁻¹ cm⁻¹. Measured values correlate with those obtained from theoretical models of the NStars using the discrete dipole approximation (DDA), which we use to simulate the extinction spectra of the nanostars. Finally, because NStars are typically used in biological applications, we conjugate DNA and antibodies to the NStars and calculate the footprint of the bound biomolecules.United States. National Institutes of Health (AI100190

Investigating the Security and Accessibility of Voyage Data Recorder Data using a USB attack

Voyage Data Recorders (VDR) or 'black boxes' for ships hold critical navigational and sensor data that can be used as evidence in an investigation. These systems have proven extremely useful in determining the cause of several previous shipping accidents. Considering the importance of the VDR and the increasing number of cyber-attacks in the maritime sector, the likelihood of it being attacked is high. This paper examines the security and accessibility of VDR data through a malicious USB device. A USB device is used after a series of tests, detailed in this paper, found it to be a viable way to compromise a VDR system. Intensive penetration testing was performed on a VDR, and this paper presents the four key highlights from the authors’ tests. The results show that real-world VDR data might not be secure from an insider threat with little to no cyber knowledge, and future VDRs may open that up to more outsider attackers. For a device like VDR, where confidentiality, integrity and availability of data are critical, a cyber-attack could therefore lead to serious repercussions.cyber-SHIP (Research England

A Conceptual Cyber-Risk Assessment of Port Infastructure

Cyber-security is a growing issue across the world, however increasing concerns are being directed at ports, as they are a hub for multiple transport operations. Ransomware has shown its potential effects in recent events, infecting logistic infrastructure at Maersk and United States of America oil pipelines. As a part of a European Union Project called Cyber-MAR, researchers have been given data from several ports on the cyber-environment of their facilities. The main goal is to raise awareness of cyber-risks in ports and potential mitigations with the novel application of a dynamic risk assessment tool (Maritine Cyber Risk Assessment or MaCRA) to ports. MaCRA methodology uses a dynamic risk model to analyse maritime risks specifically, as cyber-attacks on ships and at the ports can have hard implications in both the cyber and real world. This paper uses generalised port data to create a preliminary, conceptual cyber risk assessment of ports, to raise awareness by building general risk profiles without revealing real port vulnerabilities. From this risk assessment, the authors expect to find several high-level cyber-risks that ports may need to address, as well as some scenarios that could increase or decrease those risks. The limitation of this research is the availability of data, which is somewhat mitigated by Cyber-MAR port partners. The main goal is to raise awareness of cyber-risks in ports and potential mitigation measures with the novel application of a dynamic risk assessment tool (MaCRA) to ports. This also provides a basis for further research in Cyber-MAR, as the authors will be using simulation and more real-world data to enhance the findings in this conceptual paper

The use of cyber ranges in the maritime context: Assessing maritime-cyber risks, raising awareness, and providing training

A good defensive strategy against evolving cyber threats and cybercrimes is to raise awareness and use that awareness to prepare technical mitigation and human defense strategies. A prime way to do this is through training. While there are already many sectors employing this strategy (e.g., space, smart buildings, business IT), the maritime sector has yet to take advantage of the available cyber-range technology to assess cyber risks and create appropriate training to meet those risks. Cyber security training can come in 2 forms; the first is so security professionals can raise their awareness on the latest and most urgent issues and increase defense skill levels, and the second form is directed at non-security professionals (e.g., ship builders, crew) and the general public, who are just as affected by cyber threats, but may not have the necessary security background to deal with the issues. Conducting training programs for both requires dedicated computing infrastructure to simulate and execute effective scenarios for both sets of trainees. To this end, a cyber range (CR) provides an environment for just that. The purpose of this paper is to use studies on the concept of cyber ranges to provide evidence for why the maritime sector should embrace this technology for maritime-cyber training, and envision how they will provide maritime risk assessment and raise awareness to combat tomorrow’s threats