Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies

Montigaud, Yoann; Périnel, Sophie; Dubus, Jean‐Christophe; Leclerc, Lara; Suau, Marie; Goy, Clémence; Clotagatide, Anthony; Prévôt, Nathalie; Pourchez, Jérémie

doi:10.1038/s41598-019-42103-2

Cited by 9 publications

(7 citation statements)

References 52 publications

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“…Janssens et al developed the so-called Sophia Anatomical Infant Nose-throat (SAINT) model, which was derived from the CT scan of a 9-month-old girl of 10 kg [183]. Although the SAINT cast has been used as a model for premature neonates [93,186], its dimensions are markedly larger than those of these patients. Using similar approaches, Minnochieri et al developed a Premature Infant Nose Throat-Model (PrINT) from a 32-week gestational age infant of 1.75 kg [187] and Younquist et al generated a model from a head CT scan from a 26-week gestational age infant [188].…”

Section: In Vitro Modelsmentioning

confidence: 99%

“…Lastly, the regional lung distribution of aerosolized drugs cannot be investigated with in vitro models. Interestingly, however, Montigaud et al recently described an ex vivo model of BPD consisting of the 3D-printed SAINT model connected to a sealed enclosure containing a rabbit thorax [186]. In this model, rabbit lungs were ventilated with BPD breathing patterns generated by negative pressure; lung ventilation assessment was performed with 81m Krypton scintigraphy and regional aerosol deposition was determined by coupling 99m Tc-DTPA.…”

Section: In Vitro Modelsmentioning

confidence: 99%

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Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

et al. 2021

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Delivery of medications to preterm neonates receiving non-invasive ventilation (NIV) represents one of the most challenging scenarios for aerosol medicine. This challenge is highlighted by the undersized anatomy and the complex (patho)physiological characteristics of the lungs in such infants. Key physiological restraints include low lung volumes, low compliance, and irregular respiratory rates, which significantly reduce lung deposition. Such factors are inherent to premature birth and thus can be regarded to as the intrinsic factors that affect lung deposition. However, there are a number of extrinsic factors that also impact lung deposition: such factors include the choice of aerosol generator and its configuration within the ventilation circuit, the drug formulation, the aerosol particle size distribution, the choice of NIV type, and the patient interface between the delivery system and the patient. Together, these extrinsic factors provide an opportunity to optimize the lung deposition of therapeutic aerosols and, ultimately, the efficacy of the therapy.In this review, we first provide a comprehensive characterization of both the intrinsic and extrinsic factors affecting lung deposition in premature infants, followed by a revision of the clinical attempts to deliver therapeutic aerosols to premature neonates during NIV, which are almost exclusively related to the non-invasive delivery of surfactant aerosols. In this review, we provide clues to the interpretation of existing experimental and clinical data on neonatal aerosol delivery and we also describe a frame of measurable variables and available tools, including in vitro and in vivo models, that should be considered when developing a drug for inhalation in this important but under-served patient population.

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Section: In Vitro Modelsmentioning

confidence: 99%

Section: In Vitro Modelsmentioning

confidence: 99%

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

et al. 2021

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“…Table 2 shows an overview of the different types of models as well as sources from which cells and tissue are commonly derived. These include 2D cultured cells or 3D-organotypic lung co-cultures as well as ex vivo anatomical scaffolds or models derived from live tissue or 3D-printed using biomimetic materials ( Sucre et al, 2020 ; Montigaud et al, 2019 ; Möbius et al, 2018 ; Jiang et al, 2018 ; Leeman et al, 2019 ; Montemurro et al, 2006 ; Sucre et al, 2018 ; Knoll et al, 2013 ). Fetal primary epithelial cells isolated from human or rodent lung tissues can be cultured together with lung-derived fibroblasts or MSCs to study the effect of hyperoxia regarding the expression of transcription factors associated with pulmonary development.…”

Section: In Vitro Modelsmentioning

confidence: 99%

Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies

Giusto

Wanczyk

Jensen

et al. 2021

Disease Models &Amp; Mechanisms

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Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. In vitro models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of in vitro models to complement in vivo studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.

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“…Tissue equivalency is not only relevant for image quality assessment but also for accurate radiation dosimetry especially for charged particles where the tissue composition influences the particle interactions (Kostiukhina et al, 2017;Kostiukhina et al, 2019). Despite the ubiquitous existence of various thoracic pathologies and their imaging-based surgical and diagnostic procedures, more realistic models are required (Nardi et al, 2017;Huang et al, 2019;Montigaud et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Additively Manufactured Patient-Specific Anthropomorphic Thorax Phantom With Realistic Radiation Attenuation Properties

Hatamikia

Oberoi

Unger

et al. 2020

Front. Bioeng. Biotechnol.

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Conventional medical imaging phantoms are limited by simplified geometry and radiographic skeletal homogeneity, which confines their usability for image quality assessment and radiation dosimetry. These challenges can be addressed by additive manufacturing technology, colloquially called 3D printing, which provides accurate anatomical replication and flexibility in material manipulation. In this study, we used Computed Tomography (CT)-based modified PolyJet TM 3D printing technology to print a hollow thorax phantom simulating skeletal morphology of the patient. To achieve realistic heterogenous skeletal radiation attenuation, we developed a novel radiopaque amalgamate constituting of epoxy, polypropylene and bone meal powder in twelve different ratios. We performed CT analysis for quantification of material radiodensity (in Hounsfield Units, HU) and for identification of specific compositions corresponding to the various skeletal structures in the thorax. We filled the skeletal structures with their respective radiopaque amalgamates. The phantom and isolated 3D printed rib specimens were rescanned by CT for reproducibility tests regarding verification of radiodensity and geometry. Our results showed that structural densities in the range of 42-705HU could be achieved. The radiodensity of the reconstructed phantom was comparable to the three skeletal structures investigated in a real patient thorax CT: ribs, ventral vertebral body and dorsal vertebral body. Reproducibility tests based on physical dimensional comparison between the patient and phantom CT-based segmentation displayed 97% of overlap in the range of 0.00-4.57 mm embracing the anatomical accuracy. Thus, the additively manufactured anthropomorphic thorax phantom opens new vistas for imaging-and radiation-based patient care in precision medicine.

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Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies

Cited by 9 publications

References 52 publications

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies

Additively Manufactured Patient-Specific Anthropomorphic Thorax Phantom With Realistic Radiation Attenuation Properties

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