thumb|upright=1.0|right|Ex vivo [[brainstem specimen: A. Coronal section showing the anterior aspect of the tissue. B. Sagittal section of the left side.]]
refers to biological studies involving tissues, organs, or cells maintained outside their native organism under controlled laboratory conditions. By carefully managing factors such as temperature, oxygenation, nutrient delivery, and perfusing a nutrient solution through the tissue's vasculature, researchers sustain function long enough to conduct experiments that would be difficult or unethical in a living body. Exvivo models occupy a middle ground between in vitro () models, which typically use isolated cells, and in vivo () studies conducted inside living organisms.
Ex vivo platforms support pharmacologic screening, toxicology testing, transplant evaluation, developmental biology, and investigations of disease-mechanism research across medicine and biology, from cardiology and neuroscience to dermatology and orthopedics. Because they often use human tissues obtained from clinical procedures or biobanks, they can reduce reliance on live-animal experimentation; their utility, however, is limited by finite viability, incomplete systemic integration, and post-mortem biochemical changes that accumulate over time. The earliest perfusion studies were conducted in the mid-19thcentury, and subsequent advances in sterilization, imaging, and microfluidics have facilitated broader adoption into the 20th and 21stcenturies. Regulatory oversight depends on specimen origin: human exvivo research is subject to informed consent, whereas animal-derived models fall under institutional animal care guidelines.
Principles and definition
thumb|upright=0.9|Experimental models color-coded to indicate classification as in vivo (green), ex vivo (red), or in vitro (blue), and arranged in ascending order of [[physiological relevance
Physiological relevance refers to the extent to which an experimental system replicates the structural, mechanical, and biochemical environment of a living organism. In vivo models are conducted within living organisms, therefore rank highest in terms of physiological relevance—these models preserve the full complexity of organismal physiology. In doing so, exvivo models address some of the limitations of invitro work, such as oversimplified cellular interactions, and may help mitigate the systemic variability and complexity inherent to invivo models.
thumb|left|upright=1.0|The [[preclinical development of new bone therapies often starts with in vitro studies followed by in vivo testing. Ex vivo models, such as bone explant cultures, may serve as an intermediate approach.]]
In the preclinical development of therapies for bone diseases, for example, in vitro cell studies are typically performed prior to in vivo testing in animals, as the latter approach is more costly, time-intensive, and complex, requiring large sample sizes to yield statistically meaningful results. However, in vitro findings do not always foresee in vivo responses due to the absence of native tissue architecture, including the extracellular matrix (ECM), and the lack of physiologically relevant cell–cell as well as cell–matrix interactions. Ex vivo bone explant cultures preserve these features by maintaining tissue integrity outside the organism, and reduce the complexity of in vivo testing by excluding systemic variables, enabling controlled investigation of specific biological or mechanical factors. Klein and Hutmacher (2024) propose that a model may be classified as exvivo if it meets one or more of the following criteria:
- It preserves the native structure and composition of a cell, tissue, or organ without disrupting its cellular or extracellular components.
- It is used in therapeutic contexts where cells, organs, or tissues are removed and then reimplanted.