Host responses to implants revealed by intravital microscopy

Dondossola, Eleonora; Friedl, Peter

doi:10.1038/s41578-021-00369-x

Cited by 35 publications

(28 citation statements)

References 179 publications

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“…[48] Blood vessels can be analyzed in terms of the number, diameter, density, permeability, branch point number, and blood flow. [44,47,49] Despite its embryonic and nonmammalian nature, this is a perfect model to validate our device in vivo: [50] having a fast angiogenic response, like that occurring in mammalian tumors, [44] it allowed us to observe, in few days, a host response comparable to that obtainable in mice in weeks.…”

Section: Resultsmentioning

confidence: 99%

A Miniaturized Imaging Window to Quantify Intravital Tissue Regeneration within a 3D Microscaffold in Longitudinal Studies

Conci

Jacchetti

Sironi

et al. 2022

Advanced Optical Materials

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The biocompatibility assessment of biomaterials or the dynamic response of implanted constructs entails inflammatory events primary reflected in cell behavior at the microcirculatory system. Current protocols are based on histopathology which are over 40 years old and require the sacrifice of a huge number of laboratory animal with an unsustainable ethical burden of animal research. Intravital microscopy techniques are actually used to study implantation outcomes in real time. However, no device providing a specific tracking geometry to reposition the field of view of the microscope, for repeated analyses, exists yet. The synthetic photoresist SZ2080 is characterized here, allowing the development and in vivo validation of a miniaturized imaging window, the Microatlas, that, fabricated via two‐photon polymerization, is implanted in living chicken embryos and imaged by fluorescence microscopy 3 and 4 days after the implant. The characterization of their elastomechanical and fluorescence properties highlights planar raster spacing as the most important parameter in tuning the mechanical and spectroscopic features of the structures. The quantification of cell infiltration inside the Microatlas demonstrates its potential as novel scaffold for tissue regeneration and as beacon for 3D repositioning of the microscope field of view and correction of optical aberrations.

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Section: Resultsmentioning

confidence: 99%

A Miniaturized Imaging Window to Quantify Intravital Tissue Regeneration within a 3D Microscaffold in Longitudinal Studies

Conci

Jacchetti

Sironi

et al. 2022

Advanced Optical Materials

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“…SHG results from frequency doubling of photons when interacting with non-centrosymmetric molecules and materials, including coiled-coil or polymeric proteins (such as fibrillar collagen) and synthetic polymers (such as PCL). THG originates from frequency tripling of photons when interacting with interfaces that display a mismatch of the refractive index, such as aqueous/lipid rich structures (e.g., lipid droplets and adipocytes) or polymers, including PCL, and water or air ( Dondossola et al, 2016 ; Dondossola and Friedl, 2021 ). Although autofluorescence emitted from NAD(P) H, flavins, aromatic amino acids, and lysosomes can partially overlap with the emission of GFP, this limited background signal was not detected due to the relatively high levels of GPF expression, which required minimal laser power for excitation and consequent detection.…”

Section: Resultsmentioning

confidence: 99%

“…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 parallel, resident stromal cells, such as fibroblasts, are recruited and activated, leading to the formation of a fibrotic capsule that shields the host from the material ( Veiseh and Vegas, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although informative, this strategy lacks sensitivity and time resolution to characterize dynamic disease progression. Intravital multiphoton microscopy recently emerged as a powerful tool to complement ex vivo analyses by providing mechanistic, three-dimensional (3D), and time-resolved multiparametric insights about implant integration and failure ( Dondossola and Friedl, 2021 ). This application generates high-content biological images, which are mostly analyzed manually, including individual cell counting by eye inspection, manual measurement of distances, and qualitative identification of cellular subtypes, which imply several disadvantages.…”

Section: Introductionmentioning

confidence: 99%

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Deep Learning for Automated Analysis of Cellular and Extracellular Components of the Foreign Body Response in Multiphoton Microscopy Images

Sarti

Parlani

Díaz-Gómez

et al. 2022

Front. Bioeng. Biotechnol.

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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.

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“…[ 6 ] The varied biomaterials were applied in the fields of angiogenesis, neurogenesis, wound healing, bone regeneration, and antimicrobial therapies. [ 7 ] At present, the interaction of biomaterials and surrounding tissue after implantation still needed to further reveal (such as different components of biological materials could make active different degrees of cell adhesion, proliferation, differentiation, inflammatory response, [ 8 ] and tissue microenvironment). It restricts the selection of suitable biomaterials for tissue repair from the perspective of the symbiotic microenvironment composed of material and organism.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Revealed the Symbiosis Niche of 3D Scaffolds to Accelerate Bone Defect Healing

Qiu

Ruan

et al. 2022

Advanced Science

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Three dimension (3D) printed scaffolds have been shown to be superior in promoting tissue repair, but the cell-level specific regulatory network activated by 3D printing scaffolds with different material components to form a symbiosis niche have not been systematically revealed. Here, three typical 3D printed scaffolds, including natural polymer hydrogel (gelatin-methacryloyl, GelMA), synthetic polymer material (polycaprolactone, PCL), and bioceramic (𝜷-tricalcium phosphate, 𝜷-TCP), are fabricated to explore the regulating effect of the symbiotic microenvironment during bone healing. Enrichment analysis show that hydrogel promotes tissue regeneration and reconstruction by improving blood vessel generation by enhancing oxygen transport and red blood cell development. The PCL scaffold regulates cell proliferation and differentiation by promoting cellular senescence, cell cycle and deoxyribonucleic acid (DNA) replication pathways, accelerating the process of endochondral ossification, and the formation of callus. The 𝜷-TCP scaffold can specifically enhance the expression of osteoclast differentiation and extracellular space pathway genes to promote the differentiation of osteoclasts and promote the process of bone remodeling. In these processes, specific biomaterial properties can be used to guide cell behavior and regulate molecular network in the symbiotic microenvironment to reduce the barriers of regeneration and repair.

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Host responses to implants revealed by intravital microscopy

Cited by 35 publications

References 179 publications

A Miniaturized Imaging Window to Quantify Intravital Tissue Regeneration within a 3D Microscaffold in Longitudinal Studies

A Miniaturized Imaging Window to Quantify Intravital Tissue Regeneration within a 3D Microscaffold in Longitudinal Studies

Deep Learning for Automated Analysis of Cellular and Extracellular Components of the Foreign Body Response in Multiphoton Microscopy Images

Transcriptome Analysis Revealed the Symbiosis Niche of 3D Scaffolds to Accelerate Bone Defect Healing

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