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Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

Background: Crisis resolution teams (CRTs) offer brief, intensive home treatment for people experiencing mental health crisis. CRT implementation is highly variable; positive trial outcomes have not been reproduced in scaled-up CRT care.Aims: To evaluate a 1-year programme to improve CRTs' model fidelity in a non-masked, cluster-randomised trial (part of the Crisis team Optimisation and RElapse prevention (CORE) research programme, trial registration number: ISRCTN47185233).Method: Fifteen CRTs in England received an intervention, informed by the US Implementing Evidence-Based Practice project, involving support from a CRT facilitator, online implementation resources and regular team fidelity reviews. Ten control CRTs received no additional support. The primary outcome was patient satisfaction, measured by the Client Satisfaction Questionnaire (CSQ-8), completed by 15 patients per team at CRT discharge (n = 375). Secondary outcomes: CRT model fidelity, continuity of care, staff well-being, in-patient admissions and bed use and CRT readmissions were also evaluated.Results: All CRTs were retained in the trial. Median follow-up CSQ-8 score was 28 in each group: the adjusted average in the intervention group was higher than in the control group by 0.97 (95% CI -1.02 to 2.97) but this was not significant (P = 0.34). There were fewer in-patient admissions, lower in-patient bed use and better staff psychological health in intervention teams. Model fidelity rose in most intervention teams and was significantly higher than in control teams at follow-up. There were no significant effects for other outcomes.Conclusions: The CRT service improvement programme did not achieve its primary aim of improving patient satisfaction. It showed some promise in improving CRT model fidelity and reducing acute in-patient admissions. [ABSTRACT FROM AUTHOR]