Annual Review of Biomedical Engineering最新文献

The lymphatic vasculature plays critical roles in maintaining fluid homeostasis, transporting lipid, and facilitating immune surveillance. A growing body of work has identified lymphatic dysfunction as contributing to the severity of myriad diseases and to systemic inflammation, as well as modulating drug responses. Here, we review efforts to reconstruct lymphatic vessels in vitro toward establishing humanized, functional models to advance understanding of lymphatic biology and pathophysiology. We first review lymphatic endothelial cell biology and the biophysical lymphatic microenvironment, with a focus on features that are unique to the lymphatics and that have been used as design parameters for lymphatic-on-chip devices. We then discuss the state of the art for recapitulating lymphatic function in vitro, and we acknowledge limitations and challenges to current approaches. Finally, we discuss opportunities and the need for further development of microphysiological lymphatic systems to bridge the gap in model systems between lymphatic cell culture and animal physiology.

Physics-inspired generative models (GMs), in particular diffusion models and Poisson flow models, enhance Bayesian methods and promise great utility in medical imaging. This review examines the transformative role of such generative methods. First, a variety of physics-inspired GMs, including denoising diffusion probabilistic models, score-based diffusion models, and Poisson flow generative models (including PFGM++), are revisited, with an emphasis on their accuracy, robustness and acceleration. Then, major applications of physics-inspired GMs in medical imaging are presented, comprising image reconstruction, image generation, and image analysis. Finally, future research directions are brainstormed, including unification of physics-inspired GMs, integration with vision-language models, and potential novel applications of GMs. Since the development of generative methods has been rapid, it is hoped that this review will give peers and learners a timely snapshot of this new family of physics-driven GMs and help capitalize their enormous potential for medical imaging.

Microscale sensors and actuators have been widely explored by the scientific community to augment the functionality of conventional medical implants. However, despite the many innovative concepts proposed, a negligible fraction has successfully made the leap from concept to clinical translation. This shortfall is primarily due to the considerable disparity between academic research prototypes and market-ready products. As such, it is critically important to examine the lessons learned in successful commercialization efforts to inform early-stage translational research efforts. Here, we review the regulatory prerequisites for market approval and provide a comprehensive analysis of commercially available microimplants from a device design perspective. Our objective is to illuminate both the technological advances underlying successfully commercialized devices and the key takeaways from the commercialization process, thereby facilitating a smoother pathway from academic research to clinical impact.

Understanding interaction mechanisms within cells, tissues, and organisms is crucial for driving developments across biology and medicine. Mathematical modeling is an essential tool for simulating such biological systems. Building on experiments, mechanistic models are widely used to describe small-scale intracellular networks. The development of sequencing techniques and computational tools has recently enabled multiscale models. Combining such larger scale network modeling with mechanistic modeling provides us with an opportunity to reveal previously unknown disease mechanisms and pharmacological interventions. Here, we review systems biology models from mechanistic models to multiscale models that integrate multiple layers of cellular networks and discuss how they can be used to shed light on disease states and even wellness-related states. Additionally, we introduce several methods that increase the certainty and accuracy of model predictions. Thus, combining mechanistic models with emerging mathematical and computational techniques can provide us with increasingly powerful tools to understand disease states and inspire drug discoveries.

Despite the advances in detection, diagnosis, and treatments, cancer remains a lethal disease, claiming the lives of more than 600,000 people in the United States alone in 2024. To accelerate the development of new therapeutic strategies with improved responses, significant efforts have been made to develop microfabricated in vitro models of tumor microenvironments (TMEs) that address the limitations of animal-based cancer models. These models incorporate several advanced tissue engineering techniques to better reflect the organ- and patient-specific TMEs. Additionally, microfabricated models integrated with next-generation single-cell omics technologies provide unprecedented insights into patient's cellular and molecular heterogeneity and complexity. This review provides an overview of the recent understanding of cancer development and outlines the key TME elements that can be captured in microfabricated models to enhance their physiological relevance. We highlight the recent advances in microfabricated cancer models that reflect the unique characteristics of their organs of origin or sites of dissemination.

Cancer remains a leading cause of mortality worldwide, and the demand for improved efficacy, precision, and safety of management options has never been greater. Focused ultrasound (FUS) is a rapidly emerging strategy for nonionizing, noninvasive intervention that holds promise for the multimodal treatment of solid cancers. Owing to its versatile array of bioeffects, this technology is now being evaluated across preclinical and clinical oncology trials for tumor ablation, therapeutic delivery, radiosensitization, sonodynamic therapy, and enhancement of tumor-specific immune responses. Given the breadth of this burgeoning domain, this review places a spotlight on recent advancements in breast cancer care to exemplify the multifaceted role of FUS technology for oncology indications-outlining physical principles of FUS-mediated thermal and mechanical bioeffects, giving an overview of results from recent preclinical and clinical studies investigating FUS with and without adjunct therapeutics in primary or disseminated breast cancer settings, and offering perspectives on the future of the field.

Biochemical signals in native tissue microenvironments instruct cell behavior during many biological processes ranging from developmental morphogenesis and tissue regeneration to tumor metastasis and disease progression. The detection and characterization of these signals using spatial and highly resolved quantitative methods have revealed their existence as matricellular proteins in the matrisome, some of which are bound to the extracellular matrix while others are freely diffusing. Including these biochemical signals in engineered biomaterials can impart enhanced functionality and native-like complexity, ultimately benefiting efforts to understand, model, and treat various diseases. In this review, we discuss advances in characterizing, mimicking, and harnessing biochemical signals in developing advanced engineered biomaterials. An overview of the diverse forms in which these biochemical signals exist and their effects on intracellular signal transduction is also provided. Finally, we highlight the application of biochemically complex biomaterials in the three broadly defined areas of tissue regeneration, immunoengineering, and organoid morphogenesis.

Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.

The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas. In this review, we highlight several key factors that have contributed to the ongoing democratization of ultrasound imaging, including portable and handheld devices, recent advancements in technology, and training and education. Examples of diagnostic point-of-care ultrasound (POCUS) imaging used in emergency and critical care, gastroenterology, musculoskeletal applications, and other practices are provided for both human and veterinary medicine. Open challenges and the future of POCUS imaging are presented, including the emerging role of artificial intelligence in technology development.

Recent advances in single-cell and multicellular microfluidics technology have provided powerful tools for studying cancer biology and immunology. The ability to create controlled microenvironments, perform high-throughput screenings, and monitor cellular interactions at the single-cell level has significantly advanced our understanding of tumor biology and immune responses. We discuss cutting-edge multicellular and single-cell microfluidic technologies and methodologies utilized to investigate cancer-immune cell interactions and assess the effectiveness of immunotherapies. We explore the advantages and limitations of the wide range of 3D spheroid and single-cell microfluidic models recently developed, highlighting the various approaches in device generation and applications in immunotherapy screening for potential opportunities for point-of-care approaches.