Annual Review of Biomedical Engineering最新文献

The rise in popularity of two-photon polymerization (TPP) as an additive manufacturing technique has impacted many areas of science and engineering, particularly those related to biomedical applications. Compared with other fabrication methods used for biomedical applications, TPP offers 3D, nanometer-scale fabrication dexterity (free-form). Moreover, the existence of turnkey commercial systems has increased accessibility. In this review, we discuss the diversity of biomedical applications that have benefited from the unique features of TPP. We also present the state of the art in approaches for patterning and reading 3D TPP-fabricated structures. The reading process influences the fidelity for both in situ and ex situ characterization methods. We also review efforts to leverage machine learning to facilitate process control for TPP. Finally, we conclude with a discussion of both the current challenges and exciting opportunities for biomedical applications that lie ahead for this intriguing and emerging technology.

Preclinical modeling of human circulation has been instrumental in advancing cardiovascular medicine. Alongside clinical research, the armamentarium of computational (e.g., lumped parameter or computational fluid dynamics) and experimental (e.g., benchtop or animal) models have substantially enhanced our understanding of risk factors and root causes for circulatory diseases. Recent innovations are further disrupting the boundaries of these preclinical models toward patient-specific simulations, surgical planning, and postoperative outcome prediction. This fast-paced progress empowers preclinical modeling to increasingly delve into the intricacies of single ventricle physiology, a rare and heterogeneous congenital heart disease that remains inadequately understood. Here, we review the current landscape of preclinical modeling (computational and experimental) proposed to advance clinical management of a prominent yet complex subset of single ventricle physiology: patients who have undergone Fontan-type surgical corrections. Further, we explore recent innovations and emerging technologies that are poised to bridge the gap between preclinical Fontan modeling and clinical implementation.

Questions in cancer have engaged systems biologists for decades. During that time, the quantity of molecular data has exploded, but the need for abstractions, formal models, and simplifying insights has remained the same. This review brings together classic breakthroughs and recent findings in the field of cancer systems biology, focusing on cancer cell pathways for tumorigenesis and therapeutic response. Cancer cells mutate and transduce information from their environment to alter gene expression, metabolism, and phenotypic states. Understanding the molecular architectures that make each of these steps possible is a long-term goal of cancer systems biology pursued by iterating between quantitative models and experiments. We argue that such iteration is the best path to deploying targeted therapies intelligently so that each patient receives the maximum benefit for their cancer.

Organ-on-a-chip (OOC) and organoid technologies are at the forefront of developing sophisticated in vitro systems that replicate complex host-microbiome interactions, including those associated with vaginal health and lung infection. We explore how these technologies provide insights into host-microbiome and host-pathogen interactions and the associated immune responses. Integrating omics data and high-resolution imaging in analyzing these models enhances our understanding of host-microbiome interactions' temporal and spatial aspects, paving the way for new diagnostic and treatment strategies. This review underscores the potential of OOC and organoid technologies in elucidating the complexities of vaginal health and lung disease, which have received less attention than other organ systems in recent organoid and OCC studies. Yet, each system presents notable characteristics, rendering them ideal candidates for these designs. Additionally, this review describes the key factors associated with each organ system and how to choose the technology setup to replicate human physiology.

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant. EVMP has the potential to enhance genetic engineering efficiency, improve graft survival, and reduce posttransplant complications. This will enable genetic modifications with a vast variety of applications, while raising questions on the ethics and regulation of this emerging technology. This review provides an in-depth discussion of current methodologies for delivering genetic vectors to transplantable organs, particularly focusing on the enabling role of EVMP. Organ-by-organ analysis and key characteristics of various vector and treatment options are assessed. We offer a road map for research and clinical translation, arguing that achieving scientific benchmarks while creating anticipatory governance is necessary to secure societal benefit from this technology.

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.

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.