Mechanics-Aware Organ-on-a-Chip Platforms for Vascular and Inflammatory Diseases: From Hemodynamic Modeling and AI-Driven Phenotyping to Therapeutic Screening

BackgroundVascular diseases such as atherosclerosis, thrombosis, and intracranial aneurysms, together with systemic inflammatory conditions like sepsis, share a common pathological core: dysfunction of endothelial and epithelial barriers under simultaneous mechanical and inflammatory stress. Endothelium in arterial trees senses pathological shear, while epithelial barriers in lung and gut face injury from pathogen-associated molecular patterns (PAMPs, e.g., LPS) and cytokines. Traditional two-dimensional cultures and animal models cannot faithfully reproduce this coupled mechanical-inflammatory microenvironment, leaving major bottlenecks in mechanism dissection and drug development, and resulting in high attrition rate in clinical trials. To address these challenges, organoid and organ-on-a-chip technologies, as key components of New Approach Methodologies (NAMs), have emerged as human-relevant alternatives to animal testing by emulating physiological microenvironments and overcoming these limitations. Nevertheless, bioactive compounds identified through in silico approaches rarely undergo functional validation under physiologically relevant flow and barrier conditions, and quantitative biomechanical and morphological readouts on three-dimensional in vitro models remain underdeveloped, limiting the throughput and information content of organ-on-a-chip drug evaluation pipelines.GoalThis Research Topic aims to consolidate an emerging multimodal paradigm in which mechanics-aware organ-on-a-chip platforms serve as the central testing bed for vascular and inflammatory disease research, as well as for natural products evaluation. We particularly welcome contributions that bridge two or more of the following directions: vessel-, endothelium-, epidermis-, lung, and gut-on-a-chip system development for studying barrier dysfunction under shear and LPS-driven stress; patient-specific or chip-scale computational hemodynamic and fluid-structure interaction modelling that supports the design and operational validation of thrombosis, plaque, and aneurysm chips; quantitative mechanical readouts on chip such as traction force microscopy, optical coherence elastography, and digital image and volume correlation; deep-learning-driven phenotypic profiling of organoid and organ-on-a-chip drug responses; and identification and mechanism elucidation of natural-product and food-derived anti-inflammatory leads targeting PAMPs and TLR signaling, with functional validation on organ-on-a-chip or other three-dimensional in vitro models. The goal is to demonstrate how mechanical, computational, and AI-driven tools together advance the design, validation, and pharmacological evaluation of organ-on-a-chip systems for vascular and inflammatory diseases.Scope and Information for AuthorsWelcomed contributions cover: (1) design and validation of vessel-, endothelium-, epidermis-, lung, and gut-on-a-chip systems for vascular and inflammatory disease, including endothelial and epithelial barrier models under mechanical and inflammatory stress; (2) chip-scale computational hemodynamics and fluid-structure interaction modelling that supports the design and operational validation of thrombosis, plaque, and aneurysm chips; (3) mechanical and image-based drug-response readouts including traction force microscopy, optical coherence elastography, and digital image and volume correlation; (4) deep-learning phenotypic profiling on three-dimensional in vitro models; and (5) identification and mechanism elucidation of natural-product and food-derived anti-inflammatory leads against PAMPs and TLR signaling, with functional validation on organ-on-a-chip, organoid, or other physiologically relevant in vitro models. Accepted article types: Original Research, Review, Mini Review, Methods, and Brief Research Report. Studies confined to 2D cultures, animal models, biomaterials, or pure computational work without an organ-on-a-chip or 3D in vitro component are outside the scope. Topic editors: Xinchuan Zheng, Jiaqiu Wang, Qiwei Li Source: https://www.frontiersin.org/research-topics/82352/mechanics-aware-organ-on-a-chip-platforms-for-vascular-and-inflammatory-diseases-from-hemodynamic-modeling-and-ai-driven-phenotyping-to-therapeutic-screening