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.
Tumors with high mortality rates are still a major threat to human survival and health worldwide. In recent years, cancer immunotherapy has made rapid clinical progress in eliminating cancers by activating the host's own immune system. Particularly, the use of physiological bioactive gas molecules such as nitric oxide, carbon monoxide and hydrogen sulfide have been developed as novel immunotherapeutic strategies. In this review, we have summarized the current strategies for antitumor immunotherapy via bioactive gas molecules, targeting delivery to the tumor microenvironment. We summarize the biofunctions of bioactive gases to the immune system, then gas delivery nanocarriers for antitumor immunotherapy and the current status of the platform are presented. Furthermore, since gas could specifically respond to the ultrasound, ultrasound-assisted gas delivery is generalized as a promising potential pathway for enhanced immunotherapy. Finally, we have discussed the challenges and opportunities for bioactive gas delivery and the effects of acoustic enhanced immunotherapy in future developments and possible clinical applications.
Proteins are some of the most versatile and studied macromolecules with extensive biomedical applications. The natural and biological origin of proteins offer such materials several advantages over their synthetic counterparts, such as innate bioactivity, recognition by cells and reduced immunogenic potential. Furthermore, proteins can be easily functionalized by altering their primary amino acid sequence and can often be further self-assembled into higher order structures either spontaneously or under specific environmental conditions. This review will feature the recent advances in protein-based biomaterials in the delivery of therapeutic cargo such as small molecules, genetic material, proteins, and cells. First, we will discuss the ways in which secondary structural motifs, the building blocks of more complex proteins, have unique properties that enable them to be useful for therapeutic delivery. Next, supramolecular assemblies, such as fibers, nanoparticles, and hydrogels, made from these building blocks that are engineered to behave in a cohesive manner, are discussed. Finally, we will cover additional modifications to protein materials that impart environmental responsiveness to materials. This includes the emerging field of protein molecular robots, and relatedly, protein-based theranostic materials that combine therapeutic potential with modern imaging modalities, including near-infrared fluorescence spectroscopy (NIRF), single-photo emission computed tomography/computed tomography (SPECT/CT), positron emission tomography (PET), magnetic resonance imaging (MRI), and ultrasound/photoacoustic imaging (US/PAI).
Bone is a living composite material that has the capacity to adapt and respond to both internal and external stimuli. This capacity allows bone to adapt its structure to habitual loads and repair microdamage. Although human bone evolved to adapt to normal physiologic loading (for example from gravitational and muscle forces), these same biological pathways can potentially be activated through other types of external stimuli such as pulsed electromagnetic fields, mechanical vibration, and others. This review summarizes what is currently known about how human bone adapts to various types of external stimuli. We highlight how studies on sports-specific athletes and other exercise interventions have clarified the role of mechanical loading on bone structure. We also discuss clinical scenarios, such as spinal cord injury, where mechanical loading is drastically reduced, leading to rapid bone loss and permanent alterations to bone structure. Finally, we highlight areas of emerging research and unmet clinical need.

