Exosomes have emerged as natural nanocarriers and are advantageous in the field of nanomedicine due to their lipid bilayer membrane comprising many proteins, nucleic acids and cell debris. Exosomes are secreted from all types of living cells and play a role in cancer diagnosis and therapy because of their biological properties, such as intercellular communication, modulation of immune responses, biocompatibility and target specificity. Many studies have shown that exosomes can be engineered or modified with different therapeutic substances, including nucleic acids, proteins, drugs and other nanomaterials, to improve their specificity, efficiency and safety in nanomedicine. In this review, we summarize the methodologies of exosome biogenesis, purification, the possible mechanisms of cellular uptake and the important role of exosomes in cancer diagnosis, followed by the role of engineered exosomes in cancer therapy. Also, future trends and challenges are discussed. We strongly suggest that a clear articulation of the fundamental principles for the creation of exosome-based theranostic platforms will help reveal the unique powers of exosomes in early cancer diagnosis and therapeutics, including chemotherapy, gene therapy, immunotherapy and phototherapy.
Conventional 2D cell cultures are widely used for the development of new anticancer drugs. However, their relevance asin vitromodels is increasingly questioned as they are considered too simplistic compared to complex, three-dimensionalin vivotumors. Moreover, animal experiments are not only costly and time-consuming, but also raise ethical issues and their use for some applications has been restricted. Therefore, it becomes crucial to develop new experimental models that better capture the complexity and dynamic aspects ofin vivotumors. New approaches based on microfluidic technology are promising. This technology has indeed been used to create microphysiological systems called 'organ-on-chip' which simulate key structural and functional features of human tissues and organs. These devices have further been adapted to create cancer models giving rise to the 'cancer-on-chip' (COC) concept. In this review, we will discuss the main COC models described so far for major cancer types including lung, prostate, breast, colorectal, pancreatic, and ovarian cancers. Then, we will highlight the challenges that this technology is facing and the possible research perspectives that can arise from them.
Glioma is one of the most malignant types of cancer and most gliomas remain incurable. One of the hallmarks of glioma is its invasiveness. Furthermore, glioma cells tend to readily detach from the primary tumor and travel through the brain tissue, making complete tumor resection impossible in many cases. To expand the knowledge regarding the invasive behavior of glioma, evaluate drug resistance, and recapitulate the tumor microenvironment, various modeling strategies were proposed in the last decade, including three-dimensional (3D) biomimetic scaffold-free cultures, organ-on-chip microfluidics chips, and 3D bioprinting platforms, which allow for the investigation on patient-specific treatments. The emerging method of 3D bioprinting technology has introduced a time- and cost-efficient approach to createin vitromodels that possess the structural and functional characteristics of human organs and tissues by spatially positioning cells and bioink. Here, we review emerging 3D bioprinted models developed for recapitulating the brain environment and glioma tumors, with the purpose of probing glioma cell invasion and gliomagenesis and discuss the potential use of 4D printing and machine learning applications in glioma modelling.
Achieving local therapeutic agent concentration in the kidneys through traditional systemic administration routes have associated concerns with off-target drug effects and toxicity. Additionally, kidney diseases are often accompanied by co-morbidities in other major organs, which negatively impacts drug metabolism and clearance. To circumvent these issues, kidney-specific targeting of therapeutics aims to achieve the delivery of controlled doses of therapeutic agents, such as drugs, nucleic acids, peptides, or proteins, to kidney tissues in a safe and efficient manner. Current carrier material approaches implement macromolecular and polyplex hydrogel constructs, prodrug strategies, and nanoparticle (NP)-based delivery technologies. In the context of multidisciplinary and cross-discipline innovations, the medical and bioengineering research fields have facilitated the rapid development of kidney-targeted therapies and carrier materials. In this review, we summarize the current trends and recent advancements made in the development of carrier materials for kidney disease targeted therapies, specifically hydrogel and NP-based strategies for acute kidney disease, chronic kidney disease, and renal cell carcinoma. Additionally, we discuss the current limitations in carrier materials and their delivery mechanisms.
Physiological closed-loop control (PCLC) systems are a key enabler for automation and clinician support in medicine, including, but not limited to, patient monitoring, diagnosis, clinical decision making, and therapy delivery. Existing body of work has demonstrated that PCLC systems hold the promise to advance critical care as well as a wide range of other domains in medicine bearing profound implications in quality of life, quality of care, and human wellbeing. However, the state-of-the-art PCLC technology in critical care is associated with long-standing limitations related to its development and assessment, including (a) isolated and loop-by-loop PCLC design without sufficient account for multi-faceted patient physiology, (b) suboptimal choice of therapeutic endpoints, (c) concerns related to collective safety originating from multi-PCLC interferences, and (d) premature PCLC assessment methodology. Such limitations naturally motivate research to generate new knowledge and create innovative methods. In this perspective, we propose several high-reward opportunities that can accelerate the advances in PCLC systems, which may be explored by deep fusion and collaboration among multiple disciplines including physiological systems and signals analysis, control and estimation, machine learning and artificial intelligence, and wearable sensing and embedded computing technologies.
Ocular diseases have serious implications on patients' lives, with the majority causing blindness if left untreated. In 2020 it was estimated that 43 million people were blind worldwide which is expected to increase to 61 million by 2050. Due to the eye's complex structure and defence mechanisms, there has been an ongoing challenge to deliver drugs which can penetrate the eyes' barrier and reside at the site of action. Recent advances focus on the use of hydrogels, in particular temperature-responsive hydrogels, 'thermogels', to improve the properties of current therapies. Formulating a hydrogel-based system has shown to increase the bioavailability and biodegradability, provide a sustained release profile, enhance the drug permeation and residence time, as well as reduce the frequency of applications. This article provides a review of progress made over the past 5 years (2017-2021) using 'thermogels' for the treatment of some common or life-threatening ophthalmic conditions.
In the last decade, bioprinting has emerged as a facile technique for fabricating tissues constructs mimicking the architectural complexity and compositional heterogeneity of native tissues. Amongst different bioprinting modalities, extrusion-based bioprinting (EBB) is the most widely used technique. Coaxial bioprinting, a type of EBB, enables fabrication of concentric cell-material layers and enlarges the scope of EBB to mimic several key aspects of native tissues. Over the period of development of bioprinting, tissue constructs integrated with vascular networks, have been one of the major achievements made possible largely by coaxial bioprinting. In this review, current advancements in biofabrication of constructs with coaxial bioprinting are discussed with a focus on different bioinks that are particularly suitable for this modality. This review also expounds the properties of different bioinks suitable for coaxial bioprinting and then analyses the key achievements made by the application of coaxial bioprinting in tissue engineering, drug delivery and in-vitro disease modelling. The major limitations and future perspectives on the critical factors that will determine the ultimate clinical translation of the versatile technique are also presented to the reader.

