The liver performs a wide range of biological functions that are essential to body homeostasis. Damage to liver tissue can result in reduced organ function, and if chronic in nature can lead to organ scarring and progressive disease. Currently, donor liver transplantation is the only longterm treatment for end-stage liver disease. However, orthotopic organ transplantation suffers from several drawbacks that include organ scarcity and lifelong immunosuppression. Therefore, new therapeutic strategies are required. One promising strategy is the engineering of implantable and vascularized liver tissue. This resource could also be used to build the next generation of liver tissue models to better understand human health, disease and aging in vitro. This article reviews recent progress in the field of liver tissue bioengineering, including microfluidic-based systems, bio-printed vascularized tissue, liver spheroids and organoid models, and the induction of angiogenesis in vivo.
The repair of soft tissue defects remains a leading clinical challenge for patients with active lifestyles, unintentional falls and injuries, cancer, and age-related diseases. Tissue engineering and 3D printing have been developed over the last decades as strategies to create personalized tissue mimics by precisely depositing biomaterials and cells to fabricate static constructs. However, long-term clinical solutions call for increasing the complexity of engineered models to incorporate bioactive processes that mimic the dynamic nature of human tissues. 4D printing has therefore become a growing strategy for building soft tissue constructs that exert function with time. The critical challenge lies in balancing biologically relevant tissue-specific function with programmable material capabilities in response to environmental stimuli. This review highlights the technological advancements that have improved progress in soft tissue engineering to build complex skin, cardiovascular, nerve, skeletal muscle, and connective tissue constructs. We first discuss mechanisms for 4D material actuation through external stimuli, which, when combined with advanced additive manufacturing tools, can assemble and program responsive tissue mimics. We next address progress in engineering functional soft tissues, which are characterized by tissue type, and discuss their limitations. Finally, the challenges associated with the fabrication of next generation 4D printed soft tissues are defined, and emerging frontiers are highlighted. STATEMENT OF SIGNIFICANCE: Soft tissue regeneration remains a clinical reconstructive challenge due to the hierarchical nature and intricate mechanics of native tissue. While 3D printing is an effective strategy for short-term healing outcomes, most tissues in the human body rely on dynamic properties to support normal physiological function. 4D printing strategies offer improvements in complexity to embed tissue-specific function into bioprinted constructs. Many existing reviews thoroughly cover 4D printing technologies and stimuli; however, their applications in soft tissue engineering toward prototyping functional tissue mimics remain underexplored. This review explores programmable stimuli for 4D printed soft tissues, advancements and limitations in function classified by soft tissue type, and insights and strategies for future challenges to work toward 4D printed functional, engineered soft tissues.
Natural food pigments primarily originate from two sources: chemical synthesis and plant-derived production. With the rapid advancement of society and technology, there is a growing demand for environmentally friendly and healthy food options. Consequently, the demand for safe, nontoxic, and sustainable sources of natural pigments has risen sharply. Natural pigments are biosynthesized during the growth and metabolic processes of plant tissues, and compounds derived from these pigments exhibit a wide range of biological activities that are beneficial to human health and disease treatment. However, due to their inherent instability and low abundance, increasing research efforts have been directed toward the bioengineering of natural pigment production. This review classifies natural pigments into five major structural categories: pyrrole, isoprenoids, quinones, phenols, and betalains. Unlike previous reviews that focused on a single pigment component or specific application fields, this review systematically integrates the biosynthetic pathways, synthetic biology strategies, pharmacological activity mechanisms, and application progress in medicine, health care, and cosmetics of natural pigment-containing medicinal materials. It emphasizes their multiple potentials as "functional pigments" in the development of natural medicines. Additionally, the review combines emerging technologies such as metabolic engineering, artificial intelligence (AI)-assisted screening, and biosensing, proposing a cross-disciplinary development path from basic synthesis to high-value applications and demonstrating strong systematicity and a forward-looking nature. It provides a new integrated perspective for innovative research on natural pigment components.
This Immunobiology special issue commemorates the 30th International Complement Workshop, held for the first time in Australia. Reflecting the global reach of complement research, the Workshop brought together delegates from 24 countries and showcased a diverse range of topics including: Structural insight into complement function; Mechanisms of activation and regulation; Cell-autonomous and intracellular complement; Novel and non-canonical roles; Complement in infection and disease; and Biomarkers, diagnostics and therapeutics. In addition to invited reviews and an original research article, this issue includes all accepted abstracts from the Workshop. Together, these contributions provide a compelling snapshot of a rapidly evolving field, one that continues to expand in scope and deepen mechanistic understanding. They highlight the dynamic, interdisciplinary and collaborative nature of complement research, and set the stage for future discoveries that will translate into clinical benefit.
To provide an introduction to the uses of generative artificial intelligence (AI) and foundation models, including large language models, in the field of health technology assessment (HTA). We reviewed applications of generative AI in 3 areas: systematic literature reviews, real-world evidence, and health economic modeling. (1) Literature reviews: generative AI has the potential to assist in automating aspects of systematic literature reviews by proposing search terms, screening abstracts, extracting data, and generating code for meta-analyses; (2) real-world evidence: generative AI can facilitate automating processes and analyze large collections of real-world data, including unstructured clinical notes and imaging; (3) health economic modeling: generative AI can aid in the development of health economic models, from conceptualization to validation. Limitations in the use of foundation models and large language models include challenges surrounding their scientific rigor and reliability, the potential for bias, implications for equity, as well as nontrivial concerns regarding adherence to regulatory and ethical standards, particularly in terms of data privacy and security. Additionally, we survey the current policy landscape and provide suggestions for HTA agencies on responsibly integrating generative AI into their workflows, emphasizing the importance of human oversight and the fast-evolving nature of these tools. Although generative AI technology holds promise with respect to HTA applications, it is still undergoing rapid developments and improvements. Continued careful evaluation of their applications to HTA is required. Both developers and users of research incorporating these tools, should familiarize themselves with their current capabilities and limitations.
Scientific bias originates from both researchers and techniques. Evidence-based strategies to mitigate this bias include the assembly of diverse teams, development of rigorous experimental designs, and use of unbiased analytical techniques. Here, we highlight potential starting points to decrease bias in bioengineering research.
This review emphasizes significance of Vitamin C as an essential water-soluble antioxidant found in fruit juices and reviews its sensitivity to heat throughout processing. The goal of this review is to integrate current knowledge regarding the variables impacting Vitamin C stability and to assess non-thermal processing technologies as substitutes for traditional heat treatments. Heat processing, though effective in microbial safety, generally results in a 50-70% reduction in natural Vitamin C levels. Recent research shows that non-thermal technologies like pulsed electric field, high-pressure processing, pulsed light, ultrasonication, ultraviolet, and cold plasma deliver better Vitamin C yields often more than 90% without compromising the natural flavor, color, and nutritional integrity of fruit juices. For example, pineapple juice treated with pulsed light retained 71% Vit C against 41% through thermal pasteurization, and cold plasma-treated tomato juice retained up to 95%. Together, these non-thermal technologies provide a promising way to ensure the nutritional integrity and sensory properties of fruit juices. Future research should aim at optimizing hurdle technology for industrial applications, allowing for energy-efficient, safe, and nutrient-preserving processing of fruit beverages.
Mechanical forces act throughout the body across multiple scales, from organs and tissues to cells and molecules, playing a vital role in maintaining tissue integrity, regulating cellular functions and supporting physiological performance. Importantly, alterations in mechanical forces and properties can be hallmarks of tissue injury and disease, and can thus serve as valuable biomarkers for disease monitoring and diagnostics and can be harnessed to modulate biological processes for therapeutic benefit. This concept, termed mechanomedicine, offers an important strategy in disease diagnosis and therapy. In this Review, we first introduce biomechanics and mechanobiology as the underlying principles of mechanomedicine and outline the properties and measurements of key mechanical signatures in health and disease. We then explore the application of mechanomedicine across scales, from organ-level and tissue-level diagnostics to cellular and molecular mechanotherapeutics, including strategies for tissue regeneration and rehabilitation. Finally, we highlight challenges and opportunities in the clinical translation of mechanomedicine approaches, in particular with regards to the innovation of materials and devices, the manufacturing of cells and organoids, the definition and standardization of mechanical biomarkers, and the integration of artificial intelligence.
Sleep neuroimaging is a subfield of sleep science that goes beyond polysomnography by combining neuroimaging techniques with validated sleep research methods to characterize sleep-wake states and investigate sleep-related processes across the 24-hour day. In this article, we review the historical advancements and applications that grew out of somnography leading to current sleep neuroimaging methods. We highlight the power of somnoimages to help visualize sleep research results and communicate complex information about sleep processes. We also suggest several ways in which applying neuroimaging during sleep has opened new avenues to more fully capture the nature of sleep, uncovered mechanisms of sleep-wake regulation, and increased understanding of sleep-related processes. Current applications and future directions of sleep neuroimaging are also discussed. Sleep neuroimaging is an advanced area of research that combines brain imaging techniques with other validated sleep measures to better understand sleep. This article reviews how sleep research has evolved from basic monitoring techniques like polysomnography to modern multimodal sleep neuroimaging methods. It highlights how these new approaches provide clearer insights into sleep processes and have led to discoveries about sleep that were previously inaccessible. The article also discusses future directions for using neuroimaging to further explore sleep and its related neuronal, behavioral, and experiential processes.
Neuromorphic electronics are inspired by the human brain's compact, energy-efficient nature and its parallel-processing capabilities. Beyond the brain, the entire human nervous system, with its hierarchical structure, efficiently preprocesses complex sensory information to support high-level neural functions such as perception and memory. Emulating these biological processes, artificial nerve electronics have been developed to replicate the energy-efficient preprocessing observed in human nerves. These systems integrate sensors, artificial neurons, artificial synapses, and actuators to mimic sensory and motor functions, surpassing conventional circuits in sensor-integrated electronics. Organic synaptic transistors (OSTs) are key components in constructing artificial nerves, offering tunable synaptic plasticity for complex sensory processing and the mechanical flexibility required for applications in soft robotics and bioelectronics. Compared to traditional sensor-integrated electronics, early implementations of organic artificial nerves (OANs) incorporating OSTs have demonstrated a higher signal-to-noise ratio, lower power consumption, and simpler circuit designs along with on-device processing capabilities and precise control of actuators and biological limbs, driving progress in neuromorphic robotics and bioelectronics. This paper reviews the materials, device engineering, and system integration of the OAN design, highlights recent advancements in neuromorphic robotics and bioelectronics utilizing the OANs, and discusses current challenges and future research directions.
Artificial intelligence (AI) systems are now prevalent in our daily lives and hold promise for transforming high-stakes fields such as healthcare. Medical AI systems are showing significant potential to support diagnostics and treatment recommendations. As these systems play an increasingly significant role in clinical decision-making, ensuring transparency in their design, operation, and outcomes is essential for building trust among key stakeholders, including patients, providers, developers, and regulators. However, many systems still function as "black boxes," making it challenging for users-such as clinicians, patients, and other stakeholders-to interpret and verify their inner workings. Here, we examine the current state of transparency in medical AIs, identifying key challenges and risks these opaque systems pose. After motivating the need for transparency in all aspects of the machine learning pipeline, from training data to model development to model deployment, we explore a range of techniques that promote explainability throughout the pipeline while highlighting the importance of continual monitoring and system updates to ensure that AI systems remain reliable over time. Finally, we address the need to overcome barriers that inhibit the integration of transparency tools into clinical settings and review regulatory frameworks that prioritize transparency in emerging AI systems. Through this survey, we aim to increase awareness of current challenges and offer actionable insights for stakeholders, such as researchers, clinicians, and regulators, on how to build trustworthy and ethically responsible AI healthcare solutions.
Living bacteria can serve as biosensors for the detection of DNA in vitro and in vivo, capitalizing on their inherent ability to take up and process foreign DNA. Such bactosensors can be engineered to analyze environmental DNA, down to the single base level, from unprocessed samples, and provide a detectable output, such as fluorescence, antibiotic resistance or therapeutic release. In this Review, we first outline design strategies for bactosensors, including genetic toolkits, such as clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems, and applications in biomedicine, agriculture, food and water safety. Moreover, we examine chassis species, DNA uptake mechanisms, signal transduction and output strategies for bacterial biosensors intended for DNA analysis. We then consider performance metrics, including limit of detection, specificity and multiplexing, and provide a comparison between living and in vitro DNA biosensors for various applications, highlighting differences in sample processing, equipment, DNA integrity, theranostics and biocontainment.
Plastic is one of the threats to the environment and human health, though it has contributed to the development of society in the past 150 years. Due to its diverse properties, lightweight, strong, heat resistant, highly convenient, waterproof, corrosion-resistant, non-biodegradable, and economical, it is popular in many applications. However, its non-biodegradable nature makes it a hazardous substance, and thus, it should be eliminated. The researchers have tried to convert this waste into valuable products from carbon-based material. These carbon-based materials include carbon nanotubes, carbon spheres, carbon nanosheets, carbon nanorods, mesoporous carbons, porous carbon, carbon-spheres, graphene, and activated carbon with diverse applications. One of the applications is used in wastewater treatment. Based on the research gap, this article focuses on synthesizing carbon-based material from PET water bottles and its application in methylene blue (MB) dye adsorption. Two catalysts, citric acid and ferric nitrate, were used for carbon synthesis, which shows a maximum Langmuir adsorption capacity of 14.90 mg/g (CCA) and 13.22 mg/g (CFe), respectively. The adsorption kinetics follow PSO kinetics. The surface area observed was 8.06 and 2.12 m2/g for CCA and CFe, respectively. The synthesized carbon has a good potential for removing MB from aqueous solutions, but further research is required to find other applications of the CCA and CFe. PRACTITIONER POINTS: The article reviews the diverse synthesis methods of listed carbon-based materials and their possible applications Carbon was prepared from waste PET waste bottles using citric acid and ferric nitrate as catalysts Equilibrium isotherms, adsorption kinetics, and process thermodynamics were studied for the removal of methylene blue dye onto synthesized carbon The maximum Langmuir adsorption capacity of 14.90 mg/g (CCA) and 13.22 mg/g (CFe) was achieved The surface area observed was 8.06 and 2.12 m2/g for CCA and CFe, respectively.
Light has become an essential tool to make and manipulate living systems in the increasingly intertwined fields of cell biology and materials science. With the ever-expanding interdisciplinary nature of current scientific research and the ongoing hunt for orthogonal, high-precision stimuli for biomaterial synthesis and modification, light has emerged as the gold standard with its low cytotoxicity and high bioorthogonality, enabling the modulation of properties in both 3D space and time (that is, 4D). Not only can light govern when and where changes occur, dosage modulation permits control over the extent of material customization, providing a route to engineered constructs approaching the 4D complexity of native tissue. Recent technological innovations span advances in stereolithography, digital light processing, volumetric bioprinting, multiphoton lithography and grayscale fabrication. Material chemistries have matched pace with the technologies: novel photochemistries permit the building of dynamic materials with complex mechanical and biochemical functionalities, such as on-demand protein activation, rapid gel formation/degradation and immobilization/release of signalling factors. Herein, we discuss the union of rapid light-based manufacturing and photoresponsive chemistries and highlight future opportunities using photochemistry in the design and user-defined customization of hydrogel biomaterials. We anticipate that these areas will continue to evolve in tandem and be influenced by new insights from traditionally disparate disciplines (such as protein engineering and inorganic chemistry), facilitating further discoveries in cellular development and disease progression, as well as orchestrating advanced tissue construction.
Antibacterial resistance is an emerging problem in military medicine. Disruptions to the health care systems in war-torn countries that result from ongoing conflict can potentially exacerbate this problem and increase the risk to U.S. forces in the deployed environment. Therefore, novel therapies are needed to mitigate the impact of these potentially devastating infections on military operations. Bacteriophages are viruses that infect and kill bacteria. They can be delivered as therapeutic agents and offer a promising alternative to traditional antibiotic chemotherapy. There are several potential benefits to their use, including high specificity and comparative ease of use in the field setting. However, the process of engineering phages for military medical applications can be a laborious and time-consuming endeavor. This review examines available techniques and compares their efficacy. This review evaluates the scientific literature on the development and application of four methods of bacteriophage genome engineering and their consideration in the context of military applications. Preffered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for a systematic review of available literature that met criteria for analysis and inclusion. The research completed for this review article originated from the United States Military Academy's library "Scout" search engine, which compiles results from 254 available databases (including PubMed, Google Scholar, and SciFinder). Particular attention was focused on identifying useful mechanistic insight into the nature of the engineering technique, the ease of use, and the applicability of the technique to countering the problem of antimicrobial resistance in the military setting. A total of 52 studies were identified that met inclusion criteria following PRISMA guidelines. The bioengineering techniques analyzed included homologous recombination (12 articles), in vivo recombineering (9 articles), bacteriophage recombineering of electroporated DNA (7 articles), and the CRISPR-Cas system (10 articles). Rates of success and fidelity varied across each platform, and comparative benefits and drawbacks are considered. Each of the phage engineering techniques addressed herein varies in amount of effort and overall success rate. CRISPR-Cas-facilitated modification of phage genomes presents a highly efficient method that does not require a lengthy purification and screening process. It therefore appears to be the method best suited for military medical applications.
Electroceuticals are bioelectronic devices that provide or modulate electrical or electrochemical signals to regulate physiological functions. In particular, devices designed for energy conversion are capable of transforming electrical energy into alternative forms of energy, such as heat or light, or vice versa, thereby enabling the photoelectrochemical and electrochemical modulation of biological systems, for example, to control muscle movement or cardiac rhythm. Such energy conversion approaches offer remote control and enhanced precision, surpassing the limitations of direct tissue and cell stimulation with traditional electroceutical devices, such as pacemakers, including mechanical mismatch at interfaces and wired communication. In this Review, we explore the fundamental principles of photoelectrochemical and electrochemical modulation of cells and tissues, emphasizing behaviour under physiological conditions. We then examine the development and application of implantable bioelectronics that use photoelectrochemical and electrochemical processes for modulation. Finally, we discuss future directions for energy conversion devices in implantable electroceuticals.
The brain continuously receives, integrates, and responds to an influx of sensory signals emerging from the internal organs. This is mediated not only through direct neuronal connections defined by the peripheral nervous system, but also endocrine, humoral, metabolic, and immune pathways. Despite being predominantly imperceptible, the complex brain-body cross-talk is essential to maintaining physiological homeostasis. Moreover, it is increasingly recognized to play a critical role in cognitive and behavioral functions as well as in disorders of the nervous system. The functional and anatomical diversity of brain-body pathways necessitates the development of multifunctional implantable neurotechnologies that can facilitate causal studies during behavior. Although ubiquitous in studies of brain function, electrical, optical, and chemical interrogation of organ-brain circuits remains a challenge. In this review, we discuss recent developments in multifunctional implantable neurotechnologies, highlighting material selection, device architectures, integration challenges, and power and data transfer approaches necessary to establish robust bioelectronic interfaces to brain and peripheral organs suitable for long-term studies of brain-body signaling.
Gene therapy has brought hope for the treatment of previously incurable diseases, such as genetic disorders, cancers and autoimmune diseases. However, gene therapy requires efficient delivery with cell and tissue specificity, which remains challenging owing to the limited targeting and cargo-loading capacity of viral delivery vehicles, as well as immunogenicity and toxicity concerns. Extracellular vesicles can be designed as non-viral carriers for gene therapy owing to their ability to deliver multiple cargo types, including transgenes, small encoding or non-coding RNA, DNA and functional proteins. Importantly, extracellular vesicles are immunologically neutral and can cross biological barriers. In this Review, we discuss the application of extracellular vesicles in gene therapy. We outline how the inherent content of extracellular vesicles can facilitate different gene-therapy approaches and examine the design of extracellular vesicles for the loading of gene-therapy tools, targeted delivery and cargo release. Finally, we survey clinical applications of extracellular vesicles and highlight important engineering and translational challenges.
Additive manufacturing is an engineering tool that enables the creation of complex structures for biomedical use, such as for 3D scaffolds for tissue engineering and regenerative medicine and in vitro disease models for drug testing. Lithography-based techniques (e.g., digital light processing DLP, volumetric additive manufacturing VAM) have particularly advanced in recent years for the 3D processing of photoreactive resins into structured hydrogels. The aim of this review is to introduce the various light-based lithographic 3D printing methods that are being used to process hydrogels, provide a guide to lithography-based printing from bioresin selection to the optimization of print parameters, highlight examples of in vitro and/or in vivo biomedical applications of hydrogels where lithography-based approaches have been leveraged, and discuss recent advanced efforts to process hydrogels into heterogenous structures with multi-scale organization. Finally, a perspective on the challenges and opportunities ahead in this field is provided.