A 3D printed in vitro bone model for the assessment of molecular and cellular cues in metastatic neuroblastoma

2021 ◽  
Author(s):  
Sanja Aveic ◽  
Simon Janßen ◽  
Ramin Nasehi ◽  
Max Seidelmann ◽  
Michael Vogt ◽  
...  
Keyword(s):  
Metastatic Niche ◽  
Bone Model ◽  
Tumor Microenvironments ◽  
3D Printed ◽  
Heterogeneous Tumor

From PSc to CSc: modeling heterogeneous tumor microenvironments of the neuroblastoma bone metastatic niche.

Development of a Novel 3D Bioprinted In Vitro Nano Bone Model for Breast Cancer Bone Metastasis Study

2014 ◽  
Vol 1724 ◽  
Author(s):  
Benjamin Holmes ◽  
Wei Zhu ◽  
Lijie Grace Zhang
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Metastatic Breast ◽  
Bone Microstructure ◽  
Bone Model ◽  
Skeletal Complications ◽  
3D Printed ◽  
Breast Cancer Bone Metastasis

ABSTRACTBreast cancer (BrCa) is the second commonest cause of cancer-related deaths in women. The metastatic breast cancer exhibits a high affinity to bone, leading to debilitating skeletal complications associated with significant morbidity and poor prognosis. Traditional in vitro and in vivo BrCa bone metastasis models contain many inherent limitations with regards to controllability, reproducibility, and flexibility of design. Thus, the objective of this research is to use a 3D bioprinting system and nanomaterials to recreate a biomimetic and tunable bone model suitable for the effective simulation and study of metastatic BrCa invading and colonizing a bone environment. For this purpose, we designed and 3D printed a series of scaffolds, comprised of a bone microstructure and nano hydroxyapatites (nHA, inorganic nano components in bone). The size and geometry of the bone microstructure was varied with 250 and 150 µm pores, in repeating square and hexagon patterns, for a total of four different pore geometries. 3D bioprinted scaffolds were subsequently conjugated with nHA, using an acetylation chemical functionalization process and then characterized by scanning electron microscope (SEM). SEM imaging showed that our designed microfeatures were printable with the predesigned resolutions described above. Imaging further confirmed that acetylation effectively attached nHA to the surface of scaffolds and induced a nanoroughness. Metastatic BrCa cell 4 h adhesion and 1, 3 and 5 day proliferation were investigated in the bone model in vitro. The cell adhesion and proliferation results showed that all scaffolds are cytocompatible for BrCa cell growth; in particular the nHA scaffolds with small hexagonal pores had the highest cell density. Given this data, it can be stipulated that our 3D printed nHA scaffolds may make effective biomimetic environments for studying BrCa bone metastasis.

scholarly journals Recycled algae-based carbon materials as electroconductive 3D printed skeletal muscle tissue engineering scaffolds

2021 ◽  
Vol 32 (7) ◽  
Author(s):  
Selva Bilge ◽  
Emre Ergene ◽  
Ebru Talak ◽  
Seyda Gokyer ◽  
Yusuf Osman Donar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Electrical Stimulation ◽  
Muscle Tissue ◽  
Carbonaceous Material ◽  
Hydrothermal Carbonization ◽  
Skeletal Muscle Tissue ◽  
Myotube Formation ◽  
3D Printed

AbstractSkeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical conductivity was provided by carbonaceous material (CM) derived from algae-based biomass. The synthesis of this conductive and functional CM consisted of eco-friendly synthesis procedure such as pre-carbonization and multi-walled carbon nanotube (MWCNT) catalysis. CM obtained from biomass via hydrothermal carbonization (CM-03) and its ash form (CM-03K) were doped within poly(ɛ-caprolactone) (PCL) matrix and 3D printed to form scaffolds with aligned fibers for structural biomimicry. Scaffolds were seeded with C2C12 mouse myoblasts and subjected to electrical stimulation during the in vitro culture. Enhanced myotube formation was observed in electroactive groups compared to their non-conductive counterparts and it was observed that myotube formation and myotube maturity were significantly increased for CM-03 group after electrical stimulation. The results have therefore showed that the CM obtained from macroalgae biomass is a promising novel source for the production of the electrically conductive scaffolds for skeletal muscle tissue engineering.

scholarly journals 3D Printed Clamps for In Vitro Tensile Tests of Human Gracilis and the Superficial Third of Quadriceps Tendons

2021 ◽  
Vol 11 (6) ◽  
pp. 2563
Author(s):  
Ivan Grgić ◽  
Vjekoslav Wertheimer ◽  
Mirko Karakašić ◽  
Željko Ivandić
Keyword(s):  
3D Printing ◽  
Fused Deposition Modeling ◽  
Tensile Tests ◽  
Biomechanical Properties ◽  
Testing Procedure ◽  
Laboratory Equipment ◽  
Fused Deposition ◽  
Custom Made ◽  
3D Printed

Recent soft tissue studies have reported issues that occur during experimentation, such as the tissue slipping and rupturing during tensile loads, the lack of standard testing procedure and equipment, the necessity for existing laboratory equipment adaptation, etc. To overcome such issues and fulfil the need for the determination of the biomechanical properties of the human gracilis and the superficial third of the quadriceps tendons, 3D printed clamps with metric thread profile-based geometry were developed. The clamps’ geometry consists of a truncated pyramid pattern, which prevents the tendons from slipping and rupturing. The use of the thread application in the design of the clamp could be used in standard clamping development procedures, unlike in previously custom-made clamps. Fused deposition modeling (FDM) was used as a 3D printing technique, together with polylactic acid (PLA), which was used as a material for clamp printing. The design was confirmed and the experiments were conducted by using porcine and human tendons. The findings justify the usage of 3D printing technology for parts manufacturing in the case of tissue testing and establish independence from the existing machine clamp system, since it was possible to print clamps for each prepared specimen and thus reduce the time for experiment setup.

scholarly journals Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2146
Author(s):  
Jian Guan ◽  
Fu-zhen Yuan ◽  
Zi-mu Mao ◽  
Hai-lin Zhu ◽  
Lin Lin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Elastic Modulus ◽  
Chondrogenic Differentiation ◽  
Marker Genes ◽  
Self Healing ◽  
Polyethylene Glycol Diacrylate ◽  
3D Microenvironment ◽  
3D Printed

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

scholarly journals Accuracy of Guided Implant Surgery in the Edentulous Jaw Using Desktop 3D-Printed Mucosal Supported Guides

2021 ◽  
Vol 10 (3) ◽  
pp. 391
Author(s):  
Rani D’haese ◽  
Tom Vrombaut ◽  
Geert Hommez ◽  
Hugo De Bruyn ◽  
Stefan Vandeweghe
Keyword(s):  
In Vitro Study ◽  
Angular Deviation ◽  
Implant Surgery ◽  
Implant Position ◽  
Surgical Guides ◽  
Negative Effect ◽  
Bone Level ◽  
3D Printed ◽  
Implant Alignment

Purpose: The aim of this in vitro study is to evaluate the accuracy of implant position using mucosal supported surgical guides, produced by a desktop 3D printer. Methods: Ninety implants (Bone Level Roxolid, 4.1 mm × 10 mm, Straumann, Villerat, Switzerland) were placed in fifteen mandibular casts (Bonemodels, Castellón de la Plana, Spain). A mucosa-supported guide was designed and printed for each of the fifteen casts. After placement of the implants, the location was assessed by scanning the cast and scan bodies with an intra-oral scanner (Primescan®, Dentsply Sirona, York, PA, USA). Two comparisons were performed: one with the mucosa as a reference, and one where only the implants were aligned. Angular, coronal and apical deviations were measured. Results: The mean implant angular deviation for tissue and implant alignment were 3.25° (SD 1.69°) and 2.39° (SD 1.42°) respectively, the coronal deviation 0.82 mm (SD 0.43 mm) and 0.45 mm (SD 0.31 mm) and the apical deviation 0.99 mm (SD 0.45 mm) and 0.71 mm (SD 0.43 mm). All three variables were significantly different between the tissue and implant alignment (p < 0.001). Conclusion: Based on the results of this study, we conclude that guided implant surgery using desktop 3D printed mucosa-supported guides has a clinically acceptable level of accuracy. The resilience of the mucosa has a negative effect on the guide stability and increases the deviation in implant position.

scholarly journals 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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

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.

scholarly journals Three-dimensionally printed polycaprolactone/multicomponent bioactive glass scaffolds for potential application in bone tissue engineering

2020 ◽  
Vol 6 (1) ◽  
pp. 57-69
Author(s):  
Amirhosein Fathi ◽  
Farzad Kermani ◽  
Aliasghar Behnamghader ◽  
Sara Banijamali ◽  
Masoud Mozafari ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
3D Printing ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Layer By Layer ◽  
Composite Scaffolds ◽  
3D Printed ◽  
Co Doped

AbstractOver the last years, three-dimensional (3D) printing has been successfully applied to produce suitable substitutes for treating bone defects. In this work, 3D printed composite scaffolds of polycaprolactone (PCL) and strontium (Sr)- and cobalt (Co)-doped multi-component melt-derived bioactive glasses (BGs) were prepared for bone tissue engineering strategies. For this purpose, 30% of as-prepared BG particles (size <38 μm) were incorporated into PCL, and then the obtained composite mix was introduced into a 3D printing machine to fabricate layer-by-layer porous structures with the size of 12 × 12 × 2 mm3.The scaffolds were fully characterized through a series of physico-chemical and biological assays. Adding the BGs to PCL led to an improvement in the compressive strength of the fabricated scaffolds and increased their hydrophilicity. Furthermore, the PCL/BG scaffolds showed apatite-forming ability (i.e., bioactivity behavior) after being immersed in simulated body fluid (SBF). The in vitro cellular examinations revealed the cytocompatibility of the scaffolds and confirmed them as suitable substrates for the adhesion and proliferation of MG-63 osteosarcoma cells. In conclusion, 3D printed composite scaffolds made of PCL and Sr- and Co-doped BGs might be potentially-beneficial bone replacements, and the achieved results motivate further research on these materials.

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

Polymers ◽  
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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