scholarly journals Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank

2021 ◽  
Vol 11 ◽  
Author(s):  
Zilong Zhou ◽  
Lele Cong ◽  
Xianling Cong
Keyword(s):  
Three Dimensional ◽  
Patient Specific ◽  
Medical Decisions ◽  
Future Directions ◽  
Self Assembling ◽  
Key Characteristics ◽  
Recent Developments ◽  
Cancer Types ◽  
Parental Tumor

Organoids are in vitro self-assembling, organ-like, three-dimensional cellular structures that stably retain key characteristics of the respective organs. Organoids can be generated from healthy or pathological tissues derived from patients. Cancer organoid culture platforms have several advantages, including conservation of the cellular composition that captures the heterogeneity and pharmacotypic signatures of the parental tumor. This platform has provided new opportunities to fill the gap between cancer research and clinical outcomes. Clinical trials have been performed using patient-derived organoids (PDO) as a tool for personalized medical decisions to predict patients’ responses to therapeutic regimens and potentially improve treatment outcomes. Living organoid biobanks encompassing several cancer types have been established, providing a representative collection of well-characterized models that will facilitate drug development. In this review, we highlight recent developments in the generation of organoid cultures and PDO biobanks, in preclinical drug discovery, and methods to design a functional organoid-on-a-chip combined with microfluidic. In addition, we discuss the advantages as well as limitations of human organoids in patient-specific therapy and highlight possible future directions.

scholarly journals The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5499
Author(s):  
Hannah L. Smith ◽  
Stephen A. Beers ◽  
Juliet C. Gray ◽  
Janos M. Kanczler
Keyword(s):  
Three Dimensional ◽  
Chorioallantoic Membrane ◽  
3D Models ◽  
In Ovo ◽  
Future Directions ◽  
3 Dimensional ◽  
In Vivo Animal Models

Treatment for osteosarcoma (OS) has been largely unchanged for several decades, with typical therapies being a mixture of chemotherapy and surgery. Although therapeutic targets and products against cancer are being continually developed, only a limited number have proved therapeutically active in OS. Thus, the understanding of the OS microenvironment and its interactions are becoming more important in developing new therapies. Three-dimensional (3D) models are important tools in increasing our understanding of complex mechanisms and interactions, such as in OS. In this review, in vivo animal models, in vitro 3D models and in ovo chorioallantoic membrane (CAM) models, are evaluated and discussed as to their contribution in understanding the progressive nature of OS, and cancer research. We aim to provide insight and prospective future directions into the potential translation of 3D models in OS.

Impact of image reconstruction parameters when using 3D DSA reconstructions to measure intracranial aneurysms

2017 ◽  
Vol 10 (3) ◽  
pp. 285-289 ◽  
Author(s):  
Katrina L Ruedinger ◽  
David R Rutkowski ◽  
Sebastian Schafer ◽  
Alejandro Roldán-Alzate ◽  
Erick L Oberstar ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Hounsfield Unit ◽  
Ground Truth ◽  
Individual Case ◽  
Dome Height ◽  
Patient Specific ◽  
Analysis Tool ◽  
Accuracy Of Measurements ◽  
Image Characteristic

Background and purposeSafe and effective use of newly developed devices for aneurysm treatment requires the ability to make accurate measurements in the angiographic suite. Our purpose was to determine the parameters that optimize the geometric accuracy of three-dimensional (3D) vascular reconstructions.MethodsAn in vitro flow model consisting of a peristaltic pump, plastic tubing, and 3D printed patient-specific aneurysm models was used to simulate blood flow in an intracranial aneurysm. Flow rates were adjusted to match values reported in the literature for the internal carotid artery. 3D digital subtraction angiography acquisitions were obtained using a commercially available biplane angiographic system. Reconstructions were done using Edge Enhancement (EE) or Hounsfield Unit (HU) kernels and a Normal or Smooth image characteristic. Reconstructed images were analyzed using the vendor's aneurysm analysis tool. Ground truth measurements were derived from metrological scans of the models with a microCT. Aneurysm volume, surface area, dome height, minimum and maximum ostium diameter were determined for the five models.ResultsIn all cases, measurements made with the EE kernel most closely matched ground truth values. Differences in values derived from reconstructions displayed with Smooth or Normal image characteristics were small and had only little impact on the geometric parameters considered.ConclusionsReconstruction parameters impact the accuracy of measurements made using the aneurysm analysis tool of a commercially available angiographic system. Absolute differences between measurements made using reconstruction parameters determined as optimal in this study were, overall, very small. The significance of these differences, if any, will depend on the details of each individual case.

scholarly journals 3D printed patient-specific aortic root models with internal sensors for minimally invasive applications

2020 ◽  
Vol 6 (35) ◽  
pp. eabb4641 ◽  
Author(s):  
Ghazaleh Haghiashtiani ◽  
Kaiyan Qiu ◽  
Jorge D. Zhingre Sanchez ◽  
Zachary J. Fuenning ◽  
Priya Nair ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Aortic Root ◽  
Three Dimensional ◽  
Sensor Arrays ◽  
Invasive Procedure ◽  
Patient Specific ◽  
Anatomical Site ◽  
Transcatheter Aortic Valve ◽  
Critical Regions

Minimally invasive surgeries have numerous advantages, yet complications may arise from limited knowledge about the anatomical site targeted for the delivery of therapy. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure for treating aortic stenosis. Here, we demonstrate multimaterial three-dimensional printing of patient-specific soft aortic root models with internally integrated electronic sensor arrays that can augment testing for TAVR preprocedural planning. We evaluated the efficacies of the models by comparing their geometric fidelities with postoperative data from patients, as well as their in vitro hemodynamic performances in cases with and without leaflet calcifications. Furthermore, we demonstrated that internal sensor arrays can facilitate the optimization of bioprosthetic valve selections and in vitro placements via mapping of the pressures applied on the critical regions of the aortic anatomies. These models may pave exciting avenues for mitigating the risks of postoperative complications and facilitating the development of next-generation medical devices.

Peptide α-helices for synthetic nanostructures

2007 ◽  
Vol 35 (3) ◽  
pp. 487-491 ◽  
Author(s):  
M.G. Ryadnov
Keyword(s):  
Self Assembly ◽  
De Novo ◽  
Three Dimensional ◽  
Functional Materials ◽  
Protein Assemblies ◽  
Helical Peptides ◽  
Design Rules ◽  
Natural Protein ◽  
Self Assembling ◽  
Recent Developments

Supramolecular structures arising from a broad range of chemical archetypes are of great technological promise. Defining such structures at the nanoscale is crucial to access principally new types of functional materials for applications in bionanotechnology. In this vein, biomolecular self-assembly has emerged as an efficient approach for building synthetic nanostructures from the bottom up. The approach predominantly employs the spontaneous folding of biopolymers to monodisperse three-dimensional shapes that assemble into hierarchically defined mesoscale composites. An immediate interest here is the extraction of reliable rules that link the chemistry of biopolymers to the mechanisms of their assembly. Once established these can be further harnessed in designing supramolecular objects de novo. Different biopolymer classes compile a rich repertoire of assembly motifs to facilitate the synthesis of otherwise inaccessible nanostructures. Among those are peptide α-helices, ubiquitous folding elements of natural protein assemblies. These are particularly appealing candidates for prescriptive supramolecular engineering, as their well-established and conservative design rules give unmatched predictability and rationale. Recent developments of self-assembling systems based on helical peptides, including fibrous systems, nanoscale linkers and reactors will be highlighted herein.

scholarly journals An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations

2022 ◽  
Vol 2 (1) ◽  
pp. 10-27
Author(s):  
Deepankar Chakroborty ◽  
Veera K. Ojala ◽  
Anna M. Knittle ◽  
Jasmin Drexler ◽  
Mahlet Z. Tamirat ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Cellular Growth ◽  
Expression Library ◽  
Functional Genetics ◽  
Mutational Hotspots ◽  
Cancer Types

Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional screen to identify potential activating ERBB4 mutations from a randomly mutated ERBB4 expression library. Ten potentially activating ERBB4 mutations were identified and subjected to validation by functional and structural analyses. Two of the 10 ERBB4 mutants, E715K and R687K, demonstrated hyperactivity in all tested cell models and promoted cellular growth under two-dimensional and three-dimensional culture conditions. ERBB4 E715K also promoted tumor growth in in vivo Ba/F3 cell mouse allografts. Importantly, all tested ERBB4 mutants were sensitive to the pan-ERBB tyrosine kinase inhibitors afatinib, neratinib, and dacomitinib. Our data indicate that rare ERBB4 mutations are potential candidates for ERBB4-targeted therapy with pan-ERBB inhibitors. Statement of Significance: ERBB4 is a member of the ERBB family of oncogenes that is frequently mutated in different cancer types but the functional impact of its somatic mutations remains unknown. Here, we have analyzed the function of over 8,000 randomly mutated ERBB4 variants in an unbiased functional genetics screen. The data indicate the presence of rare activating ERBB4 mutations in cancer, with potential to be targeted with clinically approved pan-ERBB inhibitors.

scholarly journals In vitro 3D Model of Female Reproductive Tract: An Overview and Future Aspect

2021 ◽  
Author(s):  
Arnaud Martino Capuzzo
Keyword(s):  
Reproductive Tract ◽  
Three Dimensional ◽  
Reproductive Organs ◽  
Experimental Models ◽  
Female Reproductive Tract ◽  
Complex Interactions ◽  
Current State ◽  
Pregnancy And Delivery ◽  
Recent Developments

Hormones must be balanced and dynamically controlled for the Female Reproductive Tract (FRT) to function correctly during the menstrual cycle, pregnancy, and delivery. Gamete selection and successful transfer to the uterus, where it implants and pregnancy occurs, is supported by the mucosal epithelial lining of the FRT ovaries, uterus, cervix, fallopian tubes, and vagina. Successful implantation and placentation in humans and other animals rely on complex interactions between the embryo and a receptive female reproductive system. The FRT's recent breakthroughs in three-dimensional (3D) organoid systems now provide critical experimental models that match the organ's physiological, functional, and anatomical characteristics in vitro. This article summarizes the current state of the art on organoids generated from various parts of the FRT. The current analysis examines recent developments in the creation of organoid models of reproductive organs, as well as their future directions.

scholarly journals Patient-Specific Aortic Phantom With Tunable Compliance

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Antonio Gallarello ◽  
Andrea Palombi ◽  
Giacomo Annio ◽  
Shervanthi Homer-Vanniasinkam ◽  
Elena De Momi ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Computational Models ◽  
Three Dimensional ◽  
Complex Interventions ◽  
Patient Specific ◽  
Arch Model ◽  
Magnetic Resonance Imaging Mri ◽  
Variable Wall ◽  
Silicone Model

Abstract Validation of computational models using in vitro phantoms is a nontrivial task, especially in the replication of the mechanical properties of the vessel walls, which varies with age and pathophysiological state. In this paper, we present a novel aortic phantom reconstructed from patient-specific data with variable wall compliance that can be tuned without recreating the phantom. The three-dimensional (3D) geometry of an aortic arch was retrieved from a computed tomography angiography scan. A rubber-like silicone phantom was manufactured and connected to a compliance chamber in order to tune its compliance. A lumped resistance was also coupled with the system. The compliance of the aortic arch model was validated using the Young's modulus and characterized further with respect to clinically relevant indicators. The silicone model demonstrates that compliance can be finely tuned with this system under pulsatile flow conditions. The phantom replicated values of compliance in the physiological range. Both, the pressure curves and the asymmetrical behavior of the expansion, are in agreement with the literature. This novel design approach allows obtaining for the first time a phantom with tunable compliance. Vascular phantoms designed and developed with the methodology proposed in this paper have high potential to be used in diverse conditions. Applications include training of physicians, pre-operative trials for complex interventions, testing of medical devices for cardiovascular diseases (CVDs), and comparative Magnetic-resonance-imaging (MRI)-based computational studies.

Investigations for Wax Coated 3D Printed Hybrid Patterns for Partial Dentures

2019 ◽  
Author(s):  
Kamaljit Singh Boparai ◽  
Gurpartap Singh ◽  
Rupinder Singh ◽  
Sarabjit Singh
Keyword(s):  
Fused Deposition Modeling ◽  
Three Dimensional ◽  
Surface Hardness ◽  
Dimensional Accuracy ◽  
Acrylonitrile Butadiene Styrene ◽  
Processing Technique ◽  
Patient Specific ◽  
Fused Deposition ◽  
3D Printed

Abstract In this work, 3D printed master patterns of acrylonitrile butadiene styrene (ABS) thermoplastic material have been used for the preparation of Ni-Cr based functional prototypes as partial dentures (PD). The study started with patient specific three dimensional (3D), CAD data (fetched through scanning). This data was used for preparation of .STL file for printing of master patterns on fused deposition modeling (FDM) setup. The 3D printed master patterns were further wax coated to reduce the surface irregularities (as cost effective post processing technique). The hybrid patterns were subjected to investment casting for the preparation of Ni-Cr based PD. The finally prepared functional prototypes as PD were optimized for dimensional accuracy, surface finish and surface hardness as responses. The results are visualized and supported by photomicrographs and in-vitro analysis.

Living the heart in three dimensions: applications of 3D printing in CHD

2019 ◽  
Vol 29 (06) ◽  
pp. 733-743 ◽  
Author(s):  
Mari Nieves Velasco Forte ◽  
Tarique Hussain ◽  
Arno Roest ◽  
Gorka Gomez ◽  
Monique Jongbloed ◽  
...  
Keyword(s):  
3D Printing ◽  
Heart Surgery ◽  
Wide Spectrum ◽  
Three Dimensional ◽  
Structural Heart Disease ◽  
Medical Personnel ◽  
Three Dimensions ◽  
Patient Specific ◽  
3D Printed

AbstractAdvances in biomedical engineering have led to three-dimensional (3D)-printed models being used for a broad range of different applications. Teaching medical personnel, communicating with patients and relatives, planning complex heart surgery, or designing new techniques for repair of CHD via cardiac catheterisation are now options available using patient-specific 3D-printed models. The management of CHD can be challenging owing to the wide spectrum of morphological conditions and the differences between patients. Direct visualisation and manipulation of the patients’ individual anatomy has opened new horizons in personalised treatment, providing the possibility of performing the whole procedure in vitro beforehand, thus anticipating complications and possible outcomes. In this review, we discuss the workflow to implement 3D printing in clinical practice, the imaging modalities used for anatomical segmentation, the applications of this emerging technique in patients with structural heart disease, and its limitations and future directions.

Dexamethasone loaded bilayered 3D tubular scaffold reduces restenosis at the anastomotic site of tracheal replacement: in vitro and in vivo assessments

Nanoscale ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 4846-4858 ◽  
Author(s):  
Sang Jin Lee ◽  
Ji Suk Choi ◽  
Min Rye Eom ◽  
Ha Hyeon Jo ◽  
Il Keun Kwon ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Patient Specific ◽  
Anastomotic Site ◽  
Tubular Scaffold ◽  
Recent Developments ◽  
Tracheal Tissue ◽  
The Creation ◽  
Tracheal Replacement

Despite recent developments in the tracheal tissue engineering field, the creation of a patient specific substitute possessing both appropriate mechanical and biointerfacial properties remains challenging.

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