Development of Custom Wall-Less Cardiovascular Flow Phantoms with Tissue-Mimicking Gel

Abstract Purpose Flow phantoms are used in experimental settings to aid in the simulation of blood flow. Custom geometries are available, but current phantom materials present issues with degradability and/or mimicking the mechanical properties of human tissue. In this study, a method of fabricating custom wall-less flow phantoms from a tissue-mimicking gel using 3D printed inserts is developed. Methods A 3D blood vessel geometry example of a bifurcated artery model was 3D printed in polyvinyl alcohol, embedded in tissue-mimicking gel, and subsequently dissolved to create a phantom. Uniaxial compression testing was performed to determine the Young’s moduli of the five gel types. Angle-independent, ultrasound-based imaging modalities, Vector Flow Imaging (VFI) and Blood Speckle Imaging (BSI), were utilized for flow visualization of a straight channel phantom. Results A wall-less phantom of the bifurcated artery was fabricated with minimal bubbles and continuous flow demonstrated. Additionally, flow was visualized through a straight channel phantom by VFI and BSI. The available gel types are suitable for mimicking a variety of tissue types, including cardiac tissue and blood vessels. Conclusion Custom, tissue-mimicking flow phantoms can be fabricated using the developed methodology and have potential for use in a variety of applications, including ultrasound-based imaging methods. This is the first reported use of BSI with an in vitro flow phantom.

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Design and characterization of 3D printed, neomycin-eluting poly-L-lactide mats for wound-healing applications

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-021-06509-7 ◽

2021 ◽

Vol 32 (4) ◽

Author(s):

Mahima Singh ◽

Sriramakamal Jonnalagadda

Keyword(s):

Release Kinetics ◽

Biological Properties ◽

In Vitro Dissolution ◽

3D Printer ◽

Topical Antibiotic ◽

Young’S Moduli ◽

Base Polymer ◽

Potential Applications ◽

3D Printed

AbstractThis study evaluates the suitability of 3D printed biodegradable mats to load and deliver the topical antibiotic, neomycin, for up to 3 weeks in vitro. A 3D printer equipped with a hot melt extruder was used to print bandage-like wound coverings with porous sizes appropriate for cellular attachment and viability. The semicrystalline polyester, poly-l-lactic acid (PLLA) was used as the base polymer, coated (post-printing) with polyethylene glycols (PEGs) of MWs 400 Da, 6 kDa, or 20 kDa to enable manipulation of physicochemical and biological properties to suit intended applications. The mats were further loaded with a topical antibiotic (neomycin sulfate), and cumulative drug-release monitored for 3 weeks in vitro. Microscopic imaging as well as Scanning Electron Microscopy (SEM) studies showed pore dimensions of 100 × 400 µm. These pore dimensions were achieved without compromising mechanical strength; because of the “tough” individual fibers constituting the mat (Young’s Moduli of 50 ± 20 MPa and Elastic Elongation of 10 ± 5%). The in vitro dissolution study showed first-order release kinetics for neomycin during the first 20 h, followed by diffusion-controlled (Fickian) release for the remaining duration of the study. The release of neomycin suggested that the ability to load neomycin on to PLLA mats increases threefold, as the MW of the applied PEG coating is lowered from 20 kDa to 400 Da. Overall, this study demonstrates a successful approach to using a 3D printer to prepare porous degradable mats for antibiotic delivery with potential applications to dermal regeneration and tissue engineering.

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Fabrication of Polycaprolactone/Nano Hydroxyapatite (PCL/nHA) 3D Scaffold with Enhanced In Vitro Cell Response via Design for Additive Manufacturing (DfAM)

Polymers ◽

10.3390/polym13091394 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1394

Author(s):

Yong Sang Cho ◽

So-Jung Gwak ◽

Young-Sam Cho

Keyword(s):

Mechanical Properties ◽

Cell Response ◽

Structural Characteristics ◽

Structure Design ◽

Compressive Modulus ◽

Control Group ◽

Design For Additive Manufacturing ◽

3D Scaffold ◽

3D Printed

In this study, we investigated the dual-pore kagome-structure design of a 3D-printed scaffold with enhanced in vitro cell response and compared the mechanical properties with 3D-printed scaffolds with conventional or offset patterns. The compressive modulus of the 3D-printed scaffold with the proposed design was found to resemble that of the 3D-printed scaffold with a conventional pattern at similar pore sizes despite higher porosity. Furthermore, the compressive modulus of the proposed scaffold surpassed that of the 3D-printed scaffold with conventional and offset patterns at similar porosities owing to the structural characteristics of the kagome structure. Regarding the in vitro cell response, cell adhesion, cell growth, and ALP concentration of the proposed scaffold for 14 days was superior to those of the control group scaffolds. Consequently, we found that the mechanical properties and in vitro cell response of the 3D-printed scaffold could be improved by kagome and dual-pore structures through DfAM. Moreover, we revealed that the dual-pore structure is effective for the in vitro cell response compared to the structures possessing conventional and offset patterns.

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Theoretical prediction of mechanical properties of 3D printed Kagome honeycombs and its experimental evaluation

Proceedings of the Institution of Mechanical Engineers Part C Journal of Mechanical Engineering Science ◽

10.1177/0954406219860538 ◽

2019 ◽

Vol 233 (18) ◽

pp. 6559-6576 ◽

Cited By ~ 2

Author(s):

Xuefeng Zhu ◽

Longkun Xu ◽

Xiaochen Liu ◽

Jinting Xu ◽

Ping Hu ◽

...

Keyword(s):

Mechanical Properties ◽

Shear Modulus ◽

Tensile Testing ◽

Elastic Moduli ◽

Uniaxial Tensile ◽

Anisotropy Ratio ◽

Young’S Moduli ◽

Analytical Formulas ◽

3D Printed ◽

Printed Materials

Kagome honeycomb structure is proved to incorporate excellent mechanical and actuation performances due to its special configuration. However, until now, the mechanical properties of 3D printed Kagome honeycomb have not been investigated. Hence, the objective of this work is to explore some mechanical properties of 3D-printed Kagome honeycomb structures such as elastic properties, buckling, and so on. In this paper, the analytical formulas of some mechanical properties of Kagome honeycombs made of 3D-printed materials are given. Effective elastic moduli such as Young's modulus, shear modulus, and Poisson's ratio of orthotropic Kagome honeycombs under in-plane compression and shear are derived in analytical forms. By these formulas, we investigate the relationship of the elastic moduli, the relative density, and the shape anisotropy–ratio of 3D-printed Kagome honeycomb. By the uniaxial tensile testing, the effective Young's moduli of 3D printed materials in the lateral and longitudinal directions are obtained. Then, by the analytical formulas and the experimental results, we can predict the maximum Young's moduli and the maximum shear modulus of 3D-printed Kagome honeycombs. The isotropic behavior of 3D-printed Kagome honeycombs is investigated. We also derived the equations of the initial yield strength surfaces and the buckling surfaces. We found that the sizes of the buckling surfaces of 3D printed material are smaller than that of isotropic material. The efficiency of the presented analytical formulas is verified through the tensile testing of 3D printed Kagome honeycomb specimens.

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Membranes for Modelling Cardiac Tissue Stiffness In Vitro Based on Poly(trimethylene carbonate) and Poly(ethylene glycol) Polymers

Membranes ◽

10.3390/membranes10100274 ◽

2020 ◽

Vol 10 (10) ◽

pp. 274 ◽

Cited By ~ 1

Author(s):

Iris Allijn ◽

Marcelo Ribeiro ◽

André Poot ◽

Robert Passier ◽

Dimitrios Stamatialis

Keyword(s):

Ethylene Glycol ◽

Human Heart ◽

Cardiac Tissue ◽

Heart Tissue ◽

Trimethylene Carbonate ◽

Tissue Stiffness ◽

Poly Ethylene Glycol ◽

Young’S Moduli ◽

Poly Ethylene

Despite the increased expenditure of the pharmaceutical industry on research and development, the number of drugs for cardiovascular diseases that reaches the market is decreasing. A major issue is the limited ability of the current in vitro and experimental animal models to accurately mimic human heart disease, which hampers testing of the efficacy of potential cardiac drugs. Moreover, many non-heart-related drugs have severe adverse cardiac effects, which is a major cause of drugs’ retraction after approval. A main hurdle of current in vitro models is their inability to mimic the stiffness of in vivo cardiac tissue. For instance, poly(styrene) petri dishes, which are often used in these models, have a Young’s modulus in the order of GPa, while the stiffness of healthy human heart tissue is <50 kPa. In pathological conditions, such as scarring and fibrosis, the stiffness of heart tissue is in the >100 kPa range. In this study, we focus on developing new membranes, with a set of properties for mimicry of cardiac tissue stiffness in vitro, based on methacrylate-functionalized macromers and triblock-copolymers of poly(trimethylene carbonate) and poly(ethylene glycol). The new membranes have Young’s moduli in the hydrated state ranging from 18 kPa (healthy tissue) to 2.5 MPa (pathological tissue), and are suitable for cell contraction studies using human pluripotent stem-cell-derived cardiomyocytes. The membranes with higher hydrophilicity have low drug adsorption and low Young’s moduli and could be suitable for drug screening applications.

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Radiopaque Chitosan Ducts Fabricated by Extrusion-Based 3D Printing to Promote Healing After Pancreaticoenterostomy

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.686207 ◽

2021 ◽

Vol 9 ◽

Author(s):

Maoen Pan ◽

Chaoqian Zhao ◽

Zeya Xu ◽

Yuanyuan Yang ◽

Tianhong Teng ◽

...

Keyword(s):

Mechanical Properties ◽

Molecular Weight ◽

Pancreatic Duct ◽

Silicone Rubber ◽

The Body ◽

Molecular Weights ◽

Pancreatic Duct Stent ◽

3D Printed

Long-term placement of non-degradable silicone rubber pancreatic duct stents in the body is likely to cause inflammation and injury. Therefore, it is necessary to develop degradable and biocompatible stents to replace silicone rubber tubes as pancreatic duct stents. The purpose of our research was to verify the feasibility and biological safety of extrusion-based 3D printed radiopaque chitosan (CS) ducts for pancreaticojejunostomy. Chitosan-barium sulfate (CS-Ba) ducts with different molecular weights (low-, medium-, and high-molecular weight CS-Ba: LCS-Ba, MCS-Ba, and HCS-Ba, respectively) were soaked in vitro in simulated pancreatic juice (SPJ) (pH 8.0) with or without pancreatin for 16 weeks. Changes in their weight, water absorption rate and mechanical properties were tested regularly. The biocompatibility, degradation and radiopaque performance were verified by in vivo and in vitro experiments. The results showed that CS-Ba ducts prepared by this method had regular compact structures and good molding effects. In addition, the lower the molecular weight of the CS-Ba ducts was, the faster the degradation rate was. Extrusion-based 3D-printed CS-Ba ducts have mechanical properties that match those of soft tissue, good biocompatibility and radioopacity. In vitro studies have also shown that CS-Ba ducts can promote the growth of fibroblasts. These stents have great potential for use in pancreatic duct stent applications in the future.

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Fabrication and In Vitro Evaluation of 3D Printed Porous Polyetherimide Scaffolds for Bone Tissue Engineering

BioMed Research International ◽

10.1155/2019/2076138 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Xiongfeng Tang ◽

Yanguo Qin ◽

Xinyu Xu ◽

Deming Guo ◽

Wenli Ye ◽

...

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Cell Proliferation ◽

Cell Adhesion ◽

3D Printing ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Porous Scaffold ◽

3D Printed

For bone tissue engineering, the porous scaffold should provide a biocompatible environment for cell adhesion, proliferation, and differentiation and match the mechanical properties of native bone tissue. In this work, we fabricated porous polyetherimide (PEI) scaffolds using a three-dimensional (3D) printing system, and the pore size was set as 800 μm. The morphology of 3D PEI scaffolds was characterized by the scanning electron microscope. To investigate the mechanical properties of the 3D PEI scaffold, the compressive mechanical test was performed via an electronic universal testing system. For the in vitro cell experiment, bone marrow stromal cells (BMSCs) were cultured on the surface of the 3D PEI scaffold and PEI slice, and cytotoxicity, cell adhesion, and cell proliferation were detected to verify their biocompatibility. Besides, the alkaline phosphatase staining and Alizarin Red staining were performed on the BMSCs of different samples to evaluate the osteogenic differentiation. Through these studies, we found that the 3D PEI scaffold showed an interconnected porous structure, which was consistent with the design. The elastic modulus of the 3D PEI scaffold (941.33 ± 65.26 MPa) falls in the range of modulus for the native cancellous bone. Moreover, the cell proliferation and morphology on the 3D PEI scaffold were better than those on the PEI slice, which revealed that the porous scaffold has good biocompatibility and that no toxic substances were produced during the progress of high-temperature 3D printing. The osteogenic differentiation level of the 3D PEI scaffold and PEI slice was equal and ordinary. All of these results suggest the 3D printed PEI scaffold would be a potential strategy for bone tissue engineering.

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Biomimetic Mineralization on 3D Printed PLA Scaffolds: On the Response of Human Primary Osteoblasts Spheroids and In Vivo Implantation

Polymers ◽

10.3390/polym13010074 ◽

2020 ◽

Vol 13 (1) ◽

pp. 74

Author(s):

Marianna O. C. Maia-Pinto ◽

Ana Carolina B. Brochado ◽

Bruna Nunes Teixeira ◽

Suelen C. Sartoretto ◽

Marcelo J. Uzeda ◽

...

Keyword(s):

Mechanical Properties ◽

Growth Factors ◽

Growth Factor ◽

Biological Response ◽

Primary Osteoblast ◽

Rat Calvaria ◽

3D Printed ◽

Human Primary Osteoblast

This study aimed to assess the response of 3D printed polylactic acid (PLA) scaffolds biomimetically coated with apatite on human primary osteoblast (HOb) spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution to promote apatite deposition, and characterized by physical-chemical, morphological, and mechanical properties. PLA-CaP scaffolds with interconnected porous and mechanical properties suitable for bone repairing were produced with reproducibility. The in vitro biological response was assessed with human primary osteoblast spheroids. Increased cell adhesion and the rise of in vitro release of growth factors (Platelet-Derived Growth Factor (PDGF), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) was observed for PLA-CaP scaffolds, when pre-treated with fetal bovine serum (FBS). This pre-treatment with FBS was done in a way to enhance the adsorption of serum proteins, increasing the number of bioactive sites on the surface of scaffolds, and to partially mimic in vivo interactions. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, coated with apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 on critical-sized defects (8 mm) of rat calvaria. PLA-CaP+rhBMP2 presented higher values of newly formed bone (NFB) than other groups at all in vivo experimental periods (p < 0.05), attaining 44.85% of NFB after six months. These findings indicated two new potential candidates as alternatives to autogenous bone grafts for long-term treatment: (i) 3D-printed PLA-CaP scaffold associated with spheroids, since it can reduce the time of repair in situ by expression of biomolecules and growth factors; and (ii) 3D-printed PLA-CaP functionalized rhBMP2 scaffold, a biocompatible, bioactive biomaterial, with osteoconductivity and osteoinductivity.

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3D Printed Model of Extrahepatic Biliary Ducts for Biliary Stent Testing

Materials ◽

10.3390/ma13214788 ◽

2020 ◽

Vol 13 (21) ◽

pp. 4788

Author(s):

Joanna Thomas ◽

Sagar Patel ◽

Leia Troop ◽

Robyn Guru ◽

Nicholas Faist ◽

...

Keyword(s):

Mechanical Properties ◽

Computer Aided Design ◽

Bile Ducts ◽

Biliary Stent ◽

Metal Stents ◽

In Vitro Testing ◽

Stent Deployment ◽

3D Print ◽

3D Printed

Several inflammatory conditions of the bile ducts cause strictures that prevent the drainage of bile into the gastrointestinal tract. Non-pharmacological treatments to re-establish bile flow include plastic or self-expanding metal stents (SEMs) that are inserted in the bile ducts during endoscopic retrograde cholangiopancreatography (ERCP) procedures. The focus of this study was to 3D print an anatomically accurate model of the extrahepatic bile ducts (EHBDs) with tissue-like mechanical properties to improve in vitro testing of stent prototypes. Following generation of an EHBD model via computer aided design (CAD), we tested the ability of Formlabs SLA 3D printers to precisely print the model with polymers selected based on the desired mechanical properties. We found the printers were reliable in printing the dimensionally accurate EHBD model with candidate polymers. Next, we evaluated the mechanical properties of Formlabs Elastic (FE), Flexible (FF), and Durable (FD) resins pre- and post-exposure to water, saline, or bile acid solution at 37 °C for up to one week. FE possessed the most bile duct-like mechanical properties based on its elastic moduli, percent elongations at break, and changes in mass under all liquid exposure conditions. EHBD models printed in FE sustained no functional damage during biliary stent deployment or when tube connectors were inserted, and provided a high level of visualization of deployed stents. These results demonstrate that our 3D printed EHBD model facilitates more realistic pre-clinical in vitro testing of biliary stent prototypes.

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