Low-Cost Fabrication of Polyvinyl Alcohol-Based Personalized Vascular Phantoms for In Vitro Hemodynamic Studies: Three Applications

2020 ◽  
Vol 3 (3) ◽  
Author(s):  
Giacomo Annio ◽  
Gaia Franzetti ◽  
Mirko Bonfanti ◽  
Antonio Gallarello ◽  
Andrea Palombi ◽  
...  
Keyword(s):  
Polyvinyl Alcohol ◽  
Aortic Arch ◽  
Low Cost ◽  
Three Dimensional ◽  
Patient Specific ◽  
Imaging Research ◽  
Parametric Studies ◽  
Manufacturing Techniques

Abstract Vascular phantoms mimicking human vessels are commonly used to perform in vitro hemodynamic studies for a number of bioengineering applications, such as medical device testing, clinical simulators, and medical imaging research. Simplified geometries are useful to perform parametric studies, but accurate representations of the complexity of the in vivo system are essential in several applications as personalized features have been found to play a crucial role in the management and treatment of many vascular pathologies. Despite numerous studies employing vascular phantoms produced through different manufacturing techniques, an economically viable technique, able to generate large complex patient-specific vascular anatomies, accessible to nonspecialist laboratories, still needs to be identified. In this work, a manufacturing framework to create personalized and complex phantoms with easily accessible and affordable materials and equipment is presented. In particular, three-dimensional (3D) printing with polyvinyl alcohol (PVA) is employed to create the mold, and lost core casting is performed to create the physical model. The applicability and flexibility of the proposed fabrication protocol is demonstrated through three phantom case studies—an idealized aortic arch, a patient-specific aortic arch, and a patient-specific aortic dissection model. The phantoms were successfully manufactured in a rigid silicone, a compliant silicone, and a rigid epoxy resin, respectively; using two different 3D printers and two casting techniques, without the need of specialist equipment.

scholarly journals Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1186
Author(s):  
Bárbara Pinto ◽  
Ana C. Henriques ◽  
Patrícia M. A. Silva ◽  
Hassan Bousbaa
Keyword(s):  
Cancer Research ◽  
Low Cost ◽  
Three Dimensional ◽  
3D Culture ◽  
Comprehensive Overview ◽  
Culture Techniques ◽  
Drug Candidates ◽  
In Vivo Testing

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell–cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.

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.

Patient-derived organoids for personalized drug screening in intrahepatic cholangiocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 581-581
Author(s):  
Ricardo J. Antonia ◽  
Kan Toriguchi ◽  
Eveliina Karelehto ◽  
Dania Annuar ◽  
Luika Timmerman ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Intrahepatic Cholangiocarcinoma ◽  
Three Dimensional ◽  
Small Samples ◽  
Patient Specific ◽  
Mtor Inhibition ◽  
Drug Responses

581 Background: Despite standard treatment with gemcitabine and cisplatin, median survival for unresectable Intrahepatic Cholangiocarcinoma (ICC) is < 1 year. Clearly, novel therapeutic strategies are urgently needed. The paucity of targetable mutations in ICC and the as yet unproven benefit of genetically targeted drugs led us to ask whether a reliable clinical benefit may be revealed by patient-specific therapeutic testing in novel models of ICC. Here we describe our ability to establish patient-derived three-dimensional organoid cultures (PDO) that enable individualized identification of active single agents or drug combinations in surrogate models of ICC. Methods: To model patient-specific drug responses, we used the freshly resected ICCs from small samples of single patient tumors to generate PDXs and PDOs, small spheroidal clusters of tumor cells grown in vitro. We have employed a high-throughput drug screening platform using AI-enhanced robotics (Yamaha Motor Corporation) to identify and distribute single, uniformly sized PDOs into 384-well ultra-low adherent plates. This is coupled with a TECAN D300e drug dispenser that rapidly delivers nanoliter volumes of a 34-drug panel, thereby facilitating rapid, reliable drug response analyses. Results: Our data show that PDOs retain characteristic genomic and histological features of the patients’ tumors. Drug responses were specific to each patient tumor, but PDOs from all patients responded to a greater or lesser degree to mTOR inhibition, suggesting that this pathway is important in ICC. The responses of PDO to the mTOR inhibitor Sapanisertib (INK128), was recapitulated in the same patient’s PDX. Further, INK128 was synergistic with gemcitabine in patient 970 PDOs as well as in vivo in PDX also from patient 970. Conclusions: As it is believed that PDX can predict patient responses to drugs, our results suggest that PDO may also predict patient drug responses. The establishment of PDO may allow economical patient-specific, high throughput drug screens that could ultimately inform clinical practice. [Table: see text]

scholarly journals Low-cost, rapidly-developed, 3D printed in vitro corpus callosum model for mucopolysaccharidosis type I

F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2811 ◽  
Author(s):  
Anthony Tabet ◽  
Matthew Gardner ◽  
Sebastian Swanson ◽  
Sydney Crump ◽  
Austin McMeekin ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Release ◽  
Corpus Callosum ◽  
Low Cost ◽  
Patient Specific ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I

The rising prevalence of high throughput screening and the general inability of (1) two dimensional (2D) cell culture and (2)in vitrorelease studies to predictin vivoneurobiological and pharmacokinetic responses in humans has led to greater interest in more realistic three dimensional (3D) benchtop platforms. Advantages of 3D human cell culture over its 2D analogue, or even animal models, include taking the effects of microgeometry and long-range topological features into consideration. In the era of personalized medicine, it has become increasingly valuable to screen candidate molecules and synergistic therapeutics at a patient-specific level, in particular for diseases that manifest in highly variable ways. The lack of established standards and the relatively arbitrary choice of probing conditions has limitedin vitrodrug release to a largely qualitative assessment as opposed to a predictive, quantitative measure of pharmacokinetics and pharmacodynamics in tissue. Here we report the methods used in the rapid, low-cost development of a 3D model of a mucopolysaccharidosis type I patient’s corpus callosum, which may be used for cell culture and drug release. The CAD model is developed fromin vivobrain MRI tracing of the corpus callosum using open-source software, printed with poly (lactic-acid) on a Makerbot Replicator 5X, UV-sterilized, and coated with poly (lysine) for cellular adhesion. Adaptations of material and 3D printer for expanded applications are also discussed.

Abstract 15923: A Combined In Silico and In Vitr o Approach for Surgical Planning of Pediatric Coarctation Repair

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Fanette Chassagne ◽  
Sujatha Buddhe ◽  
Lester C Permut ◽  
David MCMULLAN ◽  
Stephen P Seslar ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Aortic Arch ◽  
In Silico ◽  
Cfd Simulation ◽  
Patch Repair ◽  
Recirculation Region ◽  
Patient Specific ◽  
Congenital Cardiac Malformation

Introduction: Coarctation of the aorta is a congenital malformation of the proximal descending aorta that results in severe narrowing of the vessel lumen. It causes significant changes in the aortic hemodynamics, including reduced blood flow and an increased pressure gradient in this area of the vasculature. When this congenital cardiac malformation is associated with aortic arch hypoplasia, a two step-surgery is proposed: first, an end-to-end anastomosis in performed to remove all the ductal tissue surrounding the coarctation, and then the aorta is longitudinally incised and patched to increase its diameter. The design of the patch, based on the surgeon’s experience, is done in the OR. A combined in silico and in vitro approach is proposed to test the possibility of a priori design of the patch. This approach would also open the door to optimization of the patch to restore physiological hemodynamics in the aorta. Methods & Results: CFD simulations of the hemodynamics in the pre-treatment aortic arch were created from the segmentation of patients’ images who received surgical treatment at Seattle Children’s Hospital. In vivo hemodynamics data were used as boundary conditions for the simulation. The design of the patch was created via an in-house code and was based on surgeons’ input: the locations of the start and the end of the lumen enlargement and the length of the aortic segment to be resected. The optimization of the patch design was performed by comparing the simulated hemodynamics (pressure drop, endothelial shear stress, size of the recirculation region, ...) before and after the patch repair. The optimized patch design was then used by the surgeon to perform the in vitro surgical treatment on a physical model of the patient’s anatomy, made in a translucent silicon rubber. The repaired anatomical model was scanned by X-ray microtomography and cast in an optically clear silicone. Time-resolved particle image velocimetry measurements were performed to characterize the post-treatment hemodynamics, and compared to the results of the CFD simulation. Conclusions: This unique in silico and in vitro approach allows surgeons to perform different repairs on patient-specific physical in vitro models and to optimize the design of the patch prior to starting the surgery.

scholarly journals Biocompatibility of Bespoke 3D-Printed Titanium Alloy Plates for Treating Acetabular Fractures

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xuezhi Lin ◽  
Xingling Xiao ◽  
Yimeng Wang ◽  
Cheng Gu ◽  
Canbin Wang ◽  
...  
Keyword(s):  
Titanium Alloy ◽  
Culture Medium ◽  
Three Dimensional ◽  
Acetabular Fractures ◽  
Three Dimensional Printing ◽  
3D Printed ◽  
Manufacturing Techniques ◽  
Dimensional Printing

Treatment of acetabular fractures is challenging, not only because of its complicated anatomy but also because of the lack of fitting plates. Personalized titanium alloy plates can be fabricated by selective laser melting (SLM) but the biocompatibility of these three-dimensional printing (3D-printed) plates remains unknown. Plates were manufactured by SLM and their cytocompatibility was assessed by observing the metabolism of L929 fibroblasts incubated with culture medium extracts using a CCK-8 assay and their morphology by light microscopy. Allergenicity was tested using a guinea pig maximization test. In addition, acute systemic toxicity of the 3D-printed plates was determined by injecting extracts from the implants into the tail veins of mice. Finally, the histocompatibility of the plates was investigated by implanting them into the dorsal muscles of rabbits. The in vitro results suggested that cytocompatibility of the 3D-printed plates was similar to that of conventional plates. The in vivo data also demonstrated histocompatibility that was comparable between the two manufacturing techniques. In conclusion, both in vivo and in vitro experiments suggested favorable biocompatibility of 3D-printed titanium alloy plates, indicating that it is a promising option for treatment of acetabular fractures.

A review of biomaterials scaffold fabrication in additive manufacturing for tissue engineering

2019 ◽  
Vol 34 (6) ◽  
pp. 415-435 ◽  
Author(s):  
Tang Mei Shick ◽  
Aini Zuhra Abdul Kadir ◽  
Nor Hasrul Akhmal Ngadiman ◽  
Azanizawati Ma’aram
Keyword(s):  
Tissue Engineering ◽  
Additive Manufacturing ◽  
Material Properties ◽  
Computer Aided Design ◽  
Three Dimensional ◽  
Scaffold Fabrication ◽  
Manufacturing Techniques ◽  
Manufacturing Technologies

The current developments in three-dimensional printing also referred as “additive manufacturing” have transformed the scenarios for modern manufacturing and engineering design processes which show greatest advantages for the fabrication of complex structures such as scaffold for tissue engineering. This review aims to introduce additive manufacturing techniques in tissue engineering, types of biomaterials used in scaffold fabrication, as well as in vitro and in vivo evaluations. Biomaterials and fabrication methods could critically affect the outcomes of scaffold mechanical properties, design architectures, and cell proliferations. In addition, an ideal scaffold aids the efficiency of cell proliferation and allows the movements of cell nutrient inside the human body with their specific material properties. This article provides comprehensive review that covers broad range of all the biomaterial types using various additive manufacturing technologies. The data were extracted from 2008 to 2018 mostly from Google Scholar, ScienceDirect, and Scopus using keywords such as “Additive Manufacturing,” “3D Printing,” “Tissue Engineering,” “Biomaterial” and “Scaffold.” A 10 years research in this area was found to be mostly focused toward obtaining an ideal scaffold by investigating the fabrication strategies, biomaterials compatibility, scaffold design effectiveness through computer-aided design modeling, and optimum printing machine parameters identification. As a conclusion, this ideal scaffold fabrication can be obtained with the combination of different materials that could enhance the material properties which performed well in optimum additive manufacturing condition. Yet, there are still many challenges from the printing methods, bioprinting and cell culturing that needs to be discovered and investigated in the future.

scholarly journals Low-cost, rapidly-developed, 3D printed in vitro corpus callosum model for mucopolysaccharidosis type I

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2811
Author(s):  
Anthony Tabet ◽  
Matthew Gardner ◽  
Sebastian Swanson ◽  
Sydney Crump ◽  
Austin McMeekin ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Release ◽  
Corpus Callosum ◽  
Low Cost ◽  
Patient Specific ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I

The rising prevalence of high throughput screening and the general inability of (1) two dimensional (2D) cell culture and (2)in vitrorelease studies to predictin vivoneurobiological and pharmacokinetic responses in humans has led to greater interest in more realistic three dimensional (3D) benchtop platforms. Advantages of 3D human cell culture over its 2D analogue, or even animal models, include taking the effects of microgeometry and long-range topological features into consideration. In the era of personalized medicine, it has become increasingly valuable to screen candidate molecules and synergistic therapeutics at a patient-specific level, in particular for diseases that manifest in highly variable ways. The lack of established standards and the relatively arbitrary choice of probing conditions has limitedin vitrodrug release to a largely qualitative assessment as opposed to a predictive, quantitative measure of pharmacokinetics and pharmacodynamics in tissue. Here we report the methods used in the rapid, low-cost development of a 3D model of a mucopolysaccharidosis type I patient’s corpus callosum, which may be used for cell culture and drug release. The CAD model is developed fromin vivobrain MRI tracing of the corpus callosum using open-source software, printed with poly (lactic-acid) on a Makerbot Replicator 5X, UV-sterilized, and coated with poly (lysine) for cellular adhesion. Adaptations of material and 3D printer for expanded applications are also discussed.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

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