Abstract
The Foreign body response (FBR) is a major unresolved challenge that compromises medical implant integration and function by inflammation and fibrotic encapsulation. Mice implanted with polymeric scaffolds coupled to intravital non-linear multiphoton microscopy acquisition enable multiparametric, longitudinal investigation of the FBR evolution and interference strategies. However, follow-up analyses based on visual localization and manual segmentation are extremely time-consuming, subject to human error, and do not allow for automated parameter extraction. We developed an integrated computational pipeline based on an innovative and versatile variant of the U-Net neural network to segment and quantify cellular and extracellular structures of interest, which is maintained across different objectives without impairing accuracy. This software for automatically detecting the elements of the FBR shows promise to unravel the complexity of this pathophysiological process.
Highlights
The penetration of a foreign material inside a host organism activates a cascade of events, defined as foreign body response (FBR), aimed to minimize its negative impact (Sheikh et al, 2015; Veiseh and Vegas, 2019)
We demonstrate how versatile a variant of the base U-Net architecture is across different objectives, with no hyperparameter tuning and in data-critical (30–50 samples) microscopy image segmentation tasks, addressing recent concerns in the literature
The bone marrow of lethally irradiated αSMA-red fluorescent protein (RFP) mice was reconstituted with green fluorescent protein (GFP) bone-derived cells, generating an αSMA-RFP/GFP mouse (Figure 2A)
Summary
The penetration of a foreign material inside a host organism activates a cascade of events, defined as foreign body response (FBR), aimed to minimize its negative impact (Sheikh et al, 2015; Veiseh and Vegas, 2019). This stepwise process initiates with vascular damage and absorption of plasma proteins to the object, followed by an acute inflammation led by neutrophils and a chronic phase sustained by macrophages and foreign body giant cells (Anderson et al, 2008; Dondossola et al, 2016; Witherel et al, 2018; Veiseh and Vegas, 2019; Gurevich et al, 2020; Dondossola and Friedl, 2022). In order to better understand the mechanisms underlying the FBR and further identify strategies that effectively reduce this phenomenon, relevant preclinical models need to be developed and outcome properly monitored, analyzed, and quantified
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