scholarly journals Bioprinting the Tumor Microenvironment with an Upgraded Consumer Stereolithographic 3D Printer

2021 ◽  
Author(s):  
Louise Breideband ◽  
Kaja Nicole Wächtershäuser ◽  
Levin Hafa ◽  
Konstantin Wieland ◽  
Achilleas Frangakis ◽  
...  

A widespread application of three-dimensional (3D) bioprinting in basic and translational research requires the accessibility to affordable printers able to produce physiologically relevant tissue models. To facilitate the use of bioprinting as a standard technique in biology, an open-source device based on a consumer-grade 3D stereolithographic (SL) printer was developed. This SL bioprinter can produce complex constructs that preserve cell viability and recapitulate the physiology of tissues. The detailed documentation of the modifications apported to the printer as well as a throughout performance analysis allow for a straightforward adoption of the device in other labs and its customization for specific applications. Given the low cost, several modified bioprinters could be simultaneously operated for a highly parallelized tissue production. To showcase the capability of the bioprinter, we produced constructs consisting of patient-derived cholangiocarcinoma organoids encapsulated in a gelatin methacrylate (GelMA)/polyethylene glycol diacrylate (PEGDA) hydrogel. A thorough characterization of different GelMA/PEGDA ratios revealed that the mechanical properties of the bioprinted tumor model can be accurately fine-tuned to mimic a specific tumor micro-environment. Immunofluorescence and gene expression analyses of tumor markers confirmed that the bioprinted synthetic hydrogel provides a flexible and adequate replacement of animal-derived reconstituted extracellular matrix.

2020 ◽  
Vol 11 (1) ◽  
pp. 12 ◽  
Author(s):  
Leila Samara S. M. Magalhães ◽  
Francisco Eroni Paz Santos ◽  
Conceição de Maria Vaz Elias ◽  
Samson Afewerki ◽  
Gustavo F. Sousa ◽  
...  

Stereolithography technology associated with the employment of photocrosslinkable, biocompatible, and bioactive hydrogels have been widely used. This method enables 3D microfabrication from images created by computer programs and allows researchers to design various complex models for tissue engineering applications. This study presents a simple and fast home-made stereolithography system developed to print layer-by-layer structures. Polyethylene glycol diacrylate (PEGDA) and gelatin methacryloyl (GelMA) hydrogels were employed as the photocrosslinkable polymers in various concentrations. Three-dimensional (3D) constructions were obtained by using the stereolithography technique assembled from a commercial projector, which emphasizes the low cost and efficiency of the technique. Lithium phenyl-2,4,6-trimethylbenzoyl phosphonate (LAP) was used as a photoinitiator, and a 404 nm laser source was used to promote the crosslinking. Three-dimensional and vascularized structures with more than 5 layers and resolutions between 42 and 83 µm were printed. The 3D printed complex structures highlight the potential of this low-cost stereolithography technique as a great tool in tissue engineering studies, as an alternative to bioprint miniaturized models, simulate vital and pathological functions, and even for analyzing the actions of drugs in the human body.


2020 ◽  
Vol 9 (12) ◽  
pp. 3937
Author(s):  
Nikolaos Gkantidis ◽  
Konstantinos Dritsas ◽  
Christos Katsaros ◽  
Demetrios Halazonetis ◽  
Yijin Ren

Early diagnosis and timely management of tooth or dental material wear is imperative to avoid extensive restorations. Previous studies suggested different methods for tooth wear assessment, but no study has developed a three-dimensional (3D) superimposition technique applicable in cases where tooth surfaces, other than the occlusal, undergo extensive morphological changes. Here, we manually grinded plaster incisors and canines to simulate occlusal tooth wear of varying severity in teeth that received a wire retainer bonded on their lingual surfaces, during the assessment period. The corresponding dental casts were scanned using a surface scanner. The modified tooth crowns were best-fit approximated to the original crowns using seven 3D superimposition techniques (two reference areas with varying settings) and the gold standard technique (GS: intact adjacent teeth and alveolar processes as superimposition reference), which provided the true value. Only a specific technique (complete crown with 20% estimated overlap of meshes), which is applicable in actual clinical data, showed perfect agreement with the GS technique in all cases (median difference: −0.002, max absolute difference: 0.178 mm3). The outcomes of the suggested and the GS technique were highly reproducible (max difference < 0.040 mm3). The presented technique offers low cost, convenient, accurate, and risk-free tooth wear assessment.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1717
Author(s):  
Lei Xu ◽  
Qingliang Yang ◽  
Wei Qiang ◽  
Huijie Li ◽  
Weizhen Zhong ◽  
...  

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.


2010 ◽  
Vol 105-106 ◽  
pp. 569-571
Author(s):  
Guo Xin Tan ◽  
Cheng Yun Ning ◽  
Shu Jiang Zhang

Nanobacteria is a tiny structure with size varying 80 to 500nm, commonly occurring in clusters and producing a biofilm which contains carbonate or hydroxyl apatite. In this study, the bioactive synthetic hydrogel materials were prepared with polyethylene glycol diacrylate (PEGDA) and 2-hydroxyethyl mathacrylate (HEMA) by UV photo-polymerization. Bone marrow mesenchymal stem cells (BMSCs) were seeded onto hydrogel surface for five days. The BMSCs cell adhesion on hydrogels was confirmed by SEM to evaluate the biocompatibility of the materials. It was found groups of nanoparticles on the hydrogel surface and the particles were analyzed by SEM. The particles were analyzed for its inorganic chemical constituents using energy dispersive X-ray microanalysis (EDS). The predominant components were found to be calcium (24.40%) and phosphorus (13.98%). The most likely source of cell culture contamination by such organisms is bovine serum albumin (BSA) used as supplement in culture media. Nanobacteria in BSA may be the important factor which accelerated hydroxyapatite crystal growth on hydrogels. It is important to study the biomineralization in biological system and has potential application in biomaterials science and biotechnology.


2008 ◽  
Vol 368-372 ◽  
pp. 1175-1177 ◽  
Author(s):  
Guo Xin Tan ◽  
Ying Jun Wang ◽  
Yan Xia Guang

The bioactive synthetic hydrogel materials were prepared with polyethylene glycol diacrylate (PEGDA) and 2-hydroxyethyl mathacrylate (HEMA) by UV photo-polymerization. The aim of this study was to prepare a scaffold material by combining HEMA into a composite polymeric PEGDA-based hydrogel, which were used as bioactive artificial cartilage. The structure and properties of the synthetic hydrogels were investigated in details using FTIR techniques. The swelling data indicated that the equilibrium water content depended on the precursor feed ratio. It was found that adding the HEMA into the PEGDA-based hydrogels was very helpful to improve the swelling properties.


2017 ◽  
Vol 3 (2) ◽  
pp. 135-138 ◽  
Author(s):  
Christian Polley ◽  
Robert Mau ◽  
Clemens Lieberwirth ◽  
Jan Stenzel ◽  
Brigitte Vollmar ◽  
...  

AbstractThe deep understanding of cancer and tumor genesis, as well as the development of new therapy strategies still remains one of the emerging challenges in modern medicine. To meet these challenges it seems to be absolutely necessary to overcome the drawbacks of the established 2D in vitro models. Especially the missing microenvironment of the tumor, which means the absence of stroma and immune cells, results in a missing cell-cell and cell-stroma interaction as well as disrupted functional communication pathways. Modern 3D culture systems and 3D printing or rather bioprinting technologies attempt to solve this issue and aim to closely mimic natural tumor microenvironment. In this preliminary work we are going to present the first steps of establishing an artificial 3D tumor model utilising a low cost 3D printer. Therefore the printer had been modified with an open-source syringe pump to become a functional bioprinter using viscosity modulated alginate hydrogel. In the first attempts L929 mouse fibroblasts, which are an integral component of natural stroma, had been incorporated into the hydrogel matrix and printed into scaffolds. Subsequent to the printing process the scaffolds got ionically crosslinked with a 5% w/v aqueous solution of CaCl2 to become mechanically stable. After three days of cultivation viability testing had been performed by utilising FDG staining and PET CT to obtain a volumetric viability measurement. The viability imaging showed vital cells homogeneously distributed in the scaffold and therefore stands as an evidence for a working low cost bioprinting process and a successful first step for the development of an artificial 3D tumor model.


2013 ◽  
Vol 305 (1) ◽  
pp. C100-C110 ◽  
Author(s):  
W. J. Richardson ◽  
E. Wilson ◽  
J. E. Moore

Disease-related phenotype modulation of many cell types has been shown to be closely related to mechanical loading conditions; for example, vascular smooth muscle cell (SMC) phenotype shift from a mature, contractile state to a proliferative, synthetic state contributes to the formation of neointimal tissue during atherosclerosis and restenosis development and is related to SMC mechanical loading in vivo. The majority of past in vitro cell-stretching experiments have employed simplistic (uniform, uniaxial or biaxial) stretching environments to elucidate mechanobiological pathways involved in phenotypic shifts. However, the in vivo mechanics of the vascular wall consists of highly nonuniform stretch. Here we subjected 10T1/2 murine mesenchymal cells (an SMC precursor) to two- and three-dimensional nonuniform stretch environments. After 24 h of stretch, cells on an elastomeric membrane demonstrated varied proliferation [assessed by 5-bromo-2′-deoxyuridine (BrdU) incorporation] depending on location upon the membrane, with maximal proliferation occurring in a region of high, uniaxial stretch. Cells subjected to a nonuniform stretching regimen within three-dimensional polyethylene glycol diacrylate (PEGDA) hydrogel constructs demonstrated marked changes in mRNA expression of several phenotype-related proteins, indicating a sort of “hybrid” phenotype with contractile and synthetic markers being both upregulated and downregulated. Furthermore, expression levels of mRNAs were significantly different between various locations within the stretched gel. With the proliferation results, these data exhibit the capability of nonuniform stretching devices to induce heterogeneous cell responses, potentially indicative of spatial distributions of disease-related behaviors in vivo.


2021 ◽  
Author(s):  
RUI ZHANG ◽  
Sajjad Muhammad

Abstract BackgroundIn recent years, due to increased cranial imaging more and more small sized (diameter <2.5cm) meningiomas are diagnosed. If symptomatic then most of them need surgical removal. Exact location of the lesion is extremely important to tailor the craniotomy especially if the neuro-navigation system is not available. Many under developed countries cannot afford high costs of neuro-navigation. Hence, is relevant to discover low cost associated and effective methods to exactly locate the lesions for the surgery.MethodsBy using localization markers, we can acquire preoperative CT images of the patients, reconstruct these images into Three Dimensional (3D) virtual graphs using a computer, measure the spatial distance of the tumor from the markers, and in turn calculate the projection location of the tumor on the scalp by the Triangle Pythagorean theorem. Thereby achieving preoperative precise localization of intracranial microlesions.ResultsThe location of the tumor was consistent with that of the preoperative virtual image, and the craniotomy was exact. The patient was discharged 3 days later without any neurological deficits.ConclusionThis method is simple and reliable, inexpensive, and accurate in location of small sized lesion, which can partially compensate lack of neuro-navigationand is suitable for widespread application in hospitals in third world countries.


2018 ◽  
Vol 9 ◽  
pp. 204173141879985 ◽  
Author(s):  
Ilida Ortega Asencio ◽  
Shweta Mittar ◽  
Colin Sherborne ◽  
Ahtasham Raza ◽  
Frederik Claeyssens ◽  
...  

The continual renewal of the epidermis is thought to be related to the presence of populations of epidermal stem cells residing in physically protected microenvironments (rete ridges) directly influenced by the presence of mesenchymal fibroblasts. Current skin in vitro models do acknowledge the influence of stromal fibroblasts in skin reorganisation but the study of the effect of the rete ridge-microenvironment on epidermal renewal still remains a rich topic for exploration. We suggest there is a need for the development of new in vitro models in which to study epithelial stem cell behaviour prior to translating these models into the design of new cell-free biomaterial devices for skin reconstruction. In this study, we aimed to develop new prototype epidermal-like layers containing pseudo-rete ridge structures for studying the effect of topographical cues on epithelial cell behaviour. The models were designed using a range of three-dimensional electrospun microfabricated scaffolds. This was achieved via the utilisation of polyethylene glycol diacrylate to produce a reusable template over which poly(3-hydrroxybutyrate- co-3-hydroxyvalerate) was electrospun. Initial investigations studied the behaviour of keratinocytes cultured on models using plain scaffolds (without the presence of intricate topography) versus keratinocytes cultured on scaffolds containing microfeatures.


2020 ◽  
Vol 64 (5) ◽  
pp. 50405-1-50405-5
Author(s):  
Young-Woo Park ◽  
Myounggyu Noh

Abstract Recently, the three-dimensional (3D) printing technique has attracted much attention for creating objects of arbitrary shape and manufacturing. For the first time, in this work, we present the fabrication of an inkjet printed low-cost 3D temperature sensor on a 3D-shaped thermoplastic substrate suitable for packaging, flexible electronics, and other printed applications. The design, fabrication, and testing of a 3D printed temperature sensor are presented. The sensor pattern is designed using a computer-aided design program and fabricated by drop-on-demand inkjet printing using a magnetostrictive inkjet printhead at room temperature. The sensor pattern is printed using commercially available conductive silver nanoparticle ink. A moving speed of 90 mm/min is chosen to print the sensor pattern. The inkjet printed temperature sensor is demonstrated, and it is characterized by good electrical properties, exhibiting good sensitivity and linearity. The results indicate that 3D inkjet printing technology may have great potential for applications in sensor fabrication.


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