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3D Printing and Biomaterials for Biological and Medical Application

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 106140

Special Issue Editors


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Guest Editor
Department Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
Interests: tissue engineering; regenerative medicine; 3D printing; stem cells; exosomes; biomaterials
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Neurosciences, Dentistry Section, University of Padova, 35122 Padova, Italy
Interests: dentistry; 3D printing; tissue regeneration
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Institute of Polymers, Composites and Biomaterials, National Research Council, 80125 Naples, Italy
Interests: biomaterials; 3D printing; multifunctional scaffolds; biomimetic design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the past decade, 3D printing has emerged as a versatile technology platform for the rapid manufacturing for application on medicine. 3D printing is advantageous in terms of design freedom, automation, production speed, great accuracy, customization, and limited waste generation. By reducing the complexity of manufacturing system, designers can produce entire systems using fewer subcomponents with more complex geometries. Moreover, 3D printing has the potential to approach zero-waste manufacturing by maximizing material utilization. This novel production method enables the efficient creation and modification of physical models for validation purposes during the production process. Any design errors can be identified in advance, and the resulting changes can be introduced in the early stages of product development, eliminating the need for expensive corrections at later stages of the process. In addition, 3D printing is less wasteful in terms of both construction materials and replacement tools.

Although the direct costs of production with new methods and materials are usually higher, the flexibility offered by 3D printing substantially lowers the total cost. 3D printing is overtaking traditional machining and casting techniques for designing and manufacturing various biomedical devices. The benefits of 3D printing include not only the customization of medical products, equipment, and drugs but also increased productivity, specificity, and cost-effectiveness.

In the biomedical field, 3D printing technologies are applied in:

(1) the creation of personalized prosthetics, implants, and anatomical models;

(2) the reconstruction of organs and tissues;

(3) the manufacturing of medical instruments.

Moreover, 3D printing can be harnessed for pharmaceutical research on the dosage forms, production, and delivery of drugs and for innovative medical device manufacturing. Commercially available 3D-printed medical devices include implants (e.g., cranial plates or hip joints), external prostheses (e.g., hands), and instrumentations (e.g., guides to assist with proper surgical placement of a device).

Prof. Dr. Barbara Zavan
Prof. Stefano Sivolella
Dr. Alfredo Ronca
Guest Editors

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Keywords

  • 3D printing
  • biomaterials
  • tissue engineering
  • regenerative medicine
  • bioprinting
  • bio-ink
  • cell-laden hydrogels
  • chemically modified polymers
  • cells
  • exosomes

Published Papers (29 papers)

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15 pages, 4519 KiB  
Article
Theoretical and Experimental Assay of Shock Experienced by Yeast Cells during Laser Bioprinting
by Erika V. Grosfeld, Vyacheslav S. Zhigarkov, Alexander I. Alexandrov, Nikita V. Minaev and Vladimir I. Yusupov
Int. J. Mol. Sci. 2022, 23(17), 9823; https://doi.org/10.3390/ijms23179823 - 29 Aug 2022
Cited by 7 | Viewed by 1714
Abstract
Laser-induced forward transfer (LIFT) is a useful technique for bioprinting using gel-embedded cells. However, little is known about the stresses experienced by cells during LIFT. This paper theoretically and experimentally explores the levels of laser pulse irradiation and pulsed heating experienced by yeast [...] Read more.
Laser-induced forward transfer (LIFT) is a useful technique for bioprinting using gel-embedded cells. However, little is known about the stresses experienced by cells during LIFT. This paper theoretically and experimentally explores the levels of laser pulse irradiation and pulsed heating experienced by yeast cells during LIFT. It has been found that only 5% of the cells in the gel layer adjacent to the absorbing Ti film should be significantly heated for fractions of microseconds, which was confirmed by the fact that a corresponding population of cells died during LIFT. This was accompanied by the near-complete dimming of intracellular green fluorescent protein, also observed in response to heat shock. It is shown that microorganisms in the gel layer experience laser irradiation with an energy density of ~0.1–6 J/cm2. This level of irradiation had no effect on yeast on its own. We conclude that in a wide range of laser fluences, bioprinting kills only a minority of the cell population. Importantly, we detected a previously unobserved change in membrane permeability in viable cells. Our data provide a wider perspective on the effects of LIFT-based bioprinting on living organisms and might provide new uses for the procedure based on its effects on cell permeability. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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16 pages, 3640 KiB  
Article
Functionalized 3D-Printed ST2/Gelatin Methacryloyl/Polcaprolactone Scaffolds for Enhancing Bone Regeneration with Vascularization
by Guangliang Liu, Jie Chen, Xiaofang Wang, Yujiao Liu, Yufei Ma and Xiaolin Tu
Int. J. Mol. Sci. 2022, 23(15), 8347; https://doi.org/10.3390/ijms23158347 - 28 Jul 2022
Cited by 6 | Viewed by 2156
Abstract
Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, [...] Read more.
Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, swelling of soft tissue in the neck, etc. Therefore, safely and effectively applying growth factors in bone repair biomaterials comes to be an urgent problem that needs to be addressed. In this study, an appropriate concentration (50 ng/mL) of Wnt3a was used to pretreat the 3D-bioprinting gelatin methacryloyl(GelMA)/polycaprolactone(PCL) scaffold loaded with bone marrow stromal cell line ST2 for 24 h. This pretreatment promoted the cell proliferation, osteogenic differentiation, and mineralization of ST2 in the scaffold in vitro, and enhanced angiogenesis and osteogenesis after being implanted in critical-sized mouse calvarial defects. On the contrary, the inhibition of Wnt/β-catenin signaling in ST2 cells reduced the bone repair effect of this scaffold. These results suggested that ST2/GelMA/PCL scaffolds pretreated with an appropriate concentration of Wnt3a in culture medium could effectively enhance the osteogenic and angiogenic activity of bone repair biomaterials both in vitro and in vivo. Moreover, it would avoid the side effects caused by the supraphysiological concentrations of growth factors. This functionalized scaffold with osteogenic and angiogenic activity might be used as an outstanding bone substitute for bone regeneration and repair. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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23 pages, 3958 KiB  
Article
Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells
by Vadym Burchak, Fritz Koch, Leonard Siebler, Sonja Haase, Verena K. Horner, Xenia Kempter, G. Björn Stark, Ute Schepers, Alisa Grimm, Stefan Zimmermann, Peter Koltay, Sandra Strassburg, Günter Finkenzeller, Filip Simunovic and Florian Lampert
Int. J. Mol. Sci. 2022, 23(14), 7939; https://doi.org/10.3390/ijms23147939 - 19 Jul 2022
Cited by 7 | Viewed by 2315
Abstract
Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that [...] Read more.
Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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13 pages, 4035 KiB  
Article
Improving Printability of Digital-Light-Processing 3D Bioprinting via Photoabsorber Pigment Adjustment
by Jeong Wook Seo, Gyu Min Kim, Yejin Choi, Jae Min Cha and Hojae Bae
Int. J. Mol. Sci. 2022, 23(10), 5428; https://doi.org/10.3390/ijms23105428 - 12 May 2022
Cited by 16 | Viewed by 2957
Abstract
Digital-light-processing (DLP) three-dimensional (3D) bioprinting, which has a rapid printing speed and high precision, requires optimized biomaterial ink to ensure photocrosslinking for successful printing. However, optimization studies on DLP bioprinting have yet to sufficiently explore the measurement of light exposure energy and biomaterial [...] Read more.
Digital-light-processing (DLP) three-dimensional (3D) bioprinting, which has a rapid printing speed and high precision, requires optimized biomaterial ink to ensure photocrosslinking for successful printing. However, optimization studies on DLP bioprinting have yet to sufficiently explore the measurement of light exposure energy and biomaterial ink absorbance controls to improve the printability. In this study, we synchronized the light wavelength of the projection base printer with the absorption wavelength of the biomaterial ink. In this paper, we provide a stepwise explanation of the challenges associated with unsynchronized absorption wavelengths and provide appropriate examples. In addition to biomaterial ink wavelength synchronization, we introduce photorheological measurements, which can provide optimized light exposure conditions. The photorheological measurements provide precise numerical data on light exposure time and, therefore, are an effective alternative to the expendable and inaccurate conventional measurement methods for light exposure energy. Using both photorheological measurements and bioink wavelength synchronization, we identified essential printability optimization conditions for DLP bioprinting that can be applied to various fields of biological sciences. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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16 pages, 8235 KiB  
Article
Patients’ Stem Cells Differentiation in a 3D Environment as a Promising Experimental Tool for the Study of Amyotrophic Lateral Sclerosis
by Eveljn Scarian, Matteo Bordoni, Valentina Fantini, Emanuela Jacchetti, Manuela Teresa Raimondi, Luca Diamanti, Stephana Carelli, Cristina Cereda and Orietta Pansarasa
Int. J. Mol. Sci. 2022, 23(10), 5344; https://doi.org/10.3390/ijms23105344 - 11 May 2022
Cited by 6 | Viewed by 3051
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease (NDD) that affects motor neurons, causing weakness, muscle atrophy and spasticity. Unfortunately, there are only symptomatic treatments available. Two important innovations in recent years are three-dimensional (3D) bioprinting and induced pluripotent stem cells (iPSCs). The [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease (NDD) that affects motor neurons, causing weakness, muscle atrophy and spasticity. Unfortunately, there are only symptomatic treatments available. Two important innovations in recent years are three-dimensional (3D) bioprinting and induced pluripotent stem cells (iPSCs). The aim of this work was to demonstrate the robustness of 3D cultures for the differentiation of stem cells for the study of ALS. We reprogrammed healthy and sALS peripheral blood mononuclear cells (PBMCs) in iPSCs and differentiated them in neural stem cells (NSCs) in 2D. NSCs were printed in 3D hydrogel-based constructs and subsequently differentiated first in motor neuron progenitors and finally in motor neurons. Every step of differentiation was tested for cell viability and characterized by confocal microscopy and RT-qPCR. Finally, we tested the electrophysiological characteristics of included NSC34. We found that NSCs maintained good viability during the 3D differentiation. Our results suggest that the hydrogel does not interfere with the correct differentiation process or with the electrophysiological features of the included cells. Such evidence confirmed that 3D bioprinting can be considered a good model for the study of ALS pathogenesis. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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26 pages, 8141 KiB  
Article
Improved 3D Printing and Cell Biology Characterization of Inorganic-Filler Containing Alginate-Based Composites for Bone Regeneration: Particle Shape and Effective Surface Area Are the Dominant Factors for Printing Performance
by Vera Bednarzig, Stefan Schrüfer, Tom C. Schneider, Dirk W. Schubert, Rainer Detsch and Aldo R. Boccaccini
Int. J. Mol. Sci. 2022, 23(9), 4750; https://doi.org/10.3390/ijms23094750 - 26 Apr 2022
Cited by 12 | Viewed by 3176
Abstract
The use of organic–inorganic 3D printed composites with enhanced properties in biomedical applications continues to increase. The present study focuses on the development of 3D printed alginate-based composites incorporating inorganic fillers with different shapes (angular and round), for bone regeneration. Reactive fillers (bioactive [...] Read more.
The use of organic–inorganic 3D printed composites with enhanced properties in biomedical applications continues to increase. The present study focuses on the development of 3D printed alginate-based composites incorporating inorganic fillers with different shapes (angular and round), for bone regeneration. Reactive fillers (bioactive glass 13–93 and hydroxyapatite) and non-reactive fillers (inert soda–lime glass) were investigated. Rheological studies and the characterization of various extrusion-based parameters, including material throughput, printability, shape fidelity and filament fusion, were carried out to identify the parameters dominating the printing process. It was shown that the effective surface area of the filler particle has the highest impact on the printing behavior, while the filler reactivity presents a side aspect. Composites with angular particle morphologies showed the same high resolution during the printing process, almost independent from their reactivity, while composites with comparable amounts of round filler particles lacked stackability after printing. Further, it could be shown that a higher effective surface area of the particles can circumvent the need for a higher filler content for obtaining convincing printing results. In addition, it was proven that, by changing the particle shape, the critical filler content for the obtained adequate printability can be altered. Preliminary in vitro biocompatibility investigations were carried out with the bioactive glass containing ink. The 3D printed ink, forming an interconnected porous scaffold, was analyzed regarding its biocompatibility in direct or indirect contact with the pre-osteoblast cell line MC3T3-E1. Both kinds of cell tests showed increased viability and a high rate of proliferation, with complete coverage of the 3D scaffolds’ surface already after 7 d post cell-seeding. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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13 pages, 3118 KiB  
Article
Effects of Sterilization Methods on Different 3D Printable Materials for Templates of Physician-Modified Aortic Stent Grafts Used in Vascular Surgery—A Preliminary Study
by Paweł Rynio, Katarzyna Galant, Łukasz Wójcik, Bartłomiej Grygorcewicz, Arkadiusz Kazimierczak, Aleksander Falkowski, Piotr Gutowski, Barbara Dołęgowska and Miłosz Kawa
Int. J. Mol. Sci. 2022, 23(7), 3539; https://doi.org/10.3390/ijms23073539 - 24 Mar 2022
Cited by 14 | Viewed by 3215
Abstract
Three-dimensionally-printed aortic templates are increasingly being used to aid in the modification of stent grafts in the treatment of urgent, complex aortic disorders, often of an emergency nature. The direct contact between the aortic template and the stent graft implies the necessity of [...] Read more.
Three-dimensionally-printed aortic templates are increasingly being used to aid in the modification of stent grafts in the treatment of urgent, complex aortic disorders, often of an emergency nature. The direct contact between the aortic template and the stent graft implies the necessity of complete sterility. Currently, the efficacy of sterilizing aortic templates and the effect of sterilization on the geometry of tubular aortic models are unknown. A complex case of aortic arch dissection was selected to prepare a 3D-printed aortic arch template, which was then manufactured in six popular printing materials: polylactic acid (PLA), nylon, polypropylene (PP), polyethylene terephthalate glycol (PETG), and a rigid and flexible photopolymer resin using fused deposition modeling (FDM) and stereolithography (SLA). The 3D models were contaminated with Geobacillus stearothermophilus broth and Bacillus atrophaeus. The sterilization was performed using three different methods: heat (105 °C and 121 °C), hydrogen peroxide plasma, and ethylene oxide gas. Before and after sterilization, the aortic templates were scanned using computed tomography to detect any changes in their morphology by comparing the dimensions. All sterilization methods were effective in the elimination of microorganisms. Steam sterilization in an autoclave at 121 °C caused significant deformation of the aortic templates made of PLA, PETG, and PP. The other materials had stable geometries, and changes during mesh comparisons were found to be submillimeter. Similarly, plasma, gas, and heat at 105 °C did not change the shapes of aortic templates observed macroscopically and using mesh analysis. All mean geometry differences were smaller than 0.5 mm. All sterilization protocols tested in our study were equally effective in destroying microorganisms; however, differences occurred in the ability to induce 3D object deformation. Sterilization at high temperatures deformed aortic templates composed of PLA, PETG, and PP. This method was suitable for nylon, flexible, and rigid resin-based models. Importantly, plasma and gas sterilization were appropriate for all tested printing materials, including PLA, PETG, PP, nylon, flexible and rigid resins. Moreover, sterilization of all the printed models using our novel protocol for steam autoclaving at 105 °C was also 100% effective, which could represent a significant advantage for health centers, which can therefore use one of the most popular and cheap methods of medical equipment disinfection for the sterilization of 3D models as well. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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21 pages, 28857 KiB  
Article
Cartilage Formation In Vivo Using High Concentration Collagen-Based Bioink with MSC and Decellularized ECM Granules
by Elena V. Isaeva, Evgeny E. Beketov, Grigory A. Demyashkin, Nina D. Yakovleva, Nadezhda V. Arguchinskaya, Anastas A. Kisel, Tatiana S. Lagoda, Egor P. Malakhov, Anna N. Smirnova, Vasiliy M. Petriev, Petr S. Eremin, Egor O. Osidak, Sergey P. Domogatsky, Sergey A. Ivanov, Petr V. Shegay and Andrey D. Kaprin
Int. J. Mol. Sci. 2022, 23(5), 2703; https://doi.org/10.3390/ijms23052703 - 28 Feb 2022
Cited by 12 | Viewed by 3446
Abstract
The aim of this study was to verify the applicability of high-concentration collagen-based bioink with MSC (ADSC) and decellularized ECM granules for the formation of cartilage tissue de novo after subcutaneous implantation of the scaffolds in rats. The printability of the bioink (4% [...] Read more.
The aim of this study was to verify the applicability of high-concentration collagen-based bioink with MSC (ADSC) and decellularized ECM granules for the formation of cartilage tissue de novo after subcutaneous implantation of the scaffolds in rats. The printability of the bioink (4% collagen, 2.5% decellularized ECM granules, derived via 280 μm sieve) was shown. Three collagen-based compositions were studied: (1) with ECM; (2) with MSC; (3) with ECM and MSC. It has been established that decellularized ECM granules are able to stimulate chondrogenesis both in cell-free and MSC-laden scaffolds. Undesirable effects have been identified: bone formation as well as cartilage formation outside of the scaffold area. The key perspectives and limitations of ECM granules (powder) application have been discussed. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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36 pages, 16756 KiB  
Article
Dynamics of Endothelial Engagement and Filopodia Formation in Complex 3D Microscaffolds
by Pierre Ucla, Xingming Ju, Melisa Demircioglu, Sarah Baiz, Laurent Muller, Stéphane Germain, Catherine Monnot, Vincent Semetey and Sylvie Coscoy
Int. J. Mol. Sci. 2022, 23(5), 2415; https://doi.org/10.3390/ijms23052415 - 22 Feb 2022
Cited by 3 | Viewed by 2850
Abstract
The understanding of endothelium–extracellular matrix interactions during the initiation of new blood vessels is of great medical importance; however, the mechanobiological principles governing endothelial protrusive behaviours in 3D microtopographies remain imperfectly understood. In blood capillaries submitted to angiogenic factors (such as vascular endothelial [...] Read more.
The understanding of endothelium–extracellular matrix interactions during the initiation of new blood vessels is of great medical importance; however, the mechanobiological principles governing endothelial protrusive behaviours in 3D microtopographies remain imperfectly understood. In blood capillaries submitted to angiogenic factors (such as vascular endothelial growth factor, VEGF), endothelial cells can transiently transdifferentiate in filopodia-rich cells, named tip cells, from which angiogenesis processes are locally initiated. This protrusive state based on filopodia dynamics contrasts with the lamellipodia-based endothelial cell migration on 2D substrates. Using two-photon polymerization, we generated 3D microstructures triggering endothelial phenotypes evocative of tip cell behaviour. Hexagonal lattices on pillars (“open”), but not “closed” hexagonal lattices, induced engagement from the endothelial monolayer with the generation of numerous filopodia. The development of image analysis tools for filopodia tracking allowed to probe the influence of the microtopography (pore size, regular vs. elongated structures, role of the pillars) on orientations, engagement and filopodia dynamics, and to identify MLCK (myosin light-chain kinase) as a key player for filopodia-based protrusive mode. Importantly, these events occurred independently of VEGF treatment, suggesting that the observed phenotype was induced through microtopography. These microstructures are proposed as a model research tool for understanding endothelial cell behaviour in 3D fibrillary networks. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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12 pages, 5173 KiB  
Article
Effect of Different Filler Contents and Printing Directions on the Mechanical Properties for Photopolymer Resins
by Tamaki Hada, Manabu Kanazawa, Nanako Miyamoto, Hengyi Liu, Maiko Iwaki, Yuriko Komagamine and Shunsuke Minakuchi
Int. J. Mol. Sci. 2022, 23(4), 2296; https://doi.org/10.3390/ijms23042296 - 18 Feb 2022
Cited by 17 | Viewed by 2332
Abstract
Photopolymer resins are widely used in the production of dental prostheses, but their mechanical properties require improvement. We evaluated the effects of different zirconia filler contents and printing directions on the mechanical properties of photopolymer resin. Three-dimensional (3D) printing was used to fabricate [...] Read more.
Photopolymer resins are widely used in the production of dental prostheses, but their mechanical properties require improvement. We evaluated the effects of different zirconia filler contents and printing directions on the mechanical properties of photopolymer resin. Three-dimensional (3D) printing was used to fabricate specimens using composite photopolymers with 0 (control), 3, 5, and 10 wt.% zirconia filler. Two printing directions for fabricating rectangular specimens (25 mm × 2 mm × 2 mm) and disk-shaped specimens (φ10 mm × 2 mm) were used, 0° and 90°. Three-point bending tests were performed to determine the flexural strengths and moduli of the specimens. The Vickers hardness test was performed to determine the hardness of the specimens. Tukey’s multiple comparison tests were performed on the average values of the flexural strengths, elastic moduli, and Vickers hardness after one-way ANOVA (α = 0.05). The flexural strengths and elastic moduli at 0° from high to low were in the order of 0, 3, 10, and 5 wt.%, and those at 90° were in the order of 3, 0, 10, and 5 wt.% (p < 0.05). For 5 and 10 wt.%, no significant differences were observed in mechanical properties at 0° and 90° (p < 0.05). The Vickers hardness values at 0° and 90° from low to high were in the order of 0, 3, 5, and 10 wt.% (p < 0.05). Within the limits of this study, the optimal zirconia filler content in the photopolymer resin for 3D printing was 0 wt.% at 0° and 3 wt.% at 90°. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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14 pages, 3455 KiB  
Article
Modified Industrial Three-Dimensional Polylactic Acid Scaffold Cell Chip Promotes the Proliferation and Differentiation of Human Neural Stem Cells
by Gyeong-Ji Kim, Kwon-Jai Lee, Jeong-Woo Choi and Jeung Hee An
Int. J. Mol. Sci. 2022, 23(4), 2204; https://doi.org/10.3390/ijms23042204 - 17 Feb 2022
Cited by 5 | Viewed by 2673
Abstract
In this study, we fabricated a three-dimensional (3D) scaffold using industrial polylactic acid (PLA), which promoted the proliferation and differentiation of human neural stem cells. An industrial PLA 3D scaffold (IPTS) cell chip with a square-shaped pattern was fabricated via computer-aided design and [...] Read more.
In this study, we fabricated a three-dimensional (3D) scaffold using industrial polylactic acid (PLA), which promoted the proliferation and differentiation of human neural stem cells. An industrial PLA 3D scaffold (IPTS) cell chip with a square-shaped pattern was fabricated via computer-aided design and printed using a fused deposition modeling technique. To improve cell adhesion and cell differentiation, we coated the IPTS cell chip with gold nanoparticles (Au-NPs), nerve growth factor (NGF) protein, an NGF peptide fragment, and sonic hedgehog (SHH) protein. The proliferation of F3.Olig2 neural stem cells was increased in the IPTS cell chips coated with Au-NPs and NGF peptide fragments when compared with that of the cells cultured on non-coated IPTS cell chips. Cells cultured on the IPTS-SHH cell chip also showed high expression of motor neuron cell-specific markers, such as HB9 and TUJ-1. Therefore, we suggest that the newly engineered industrial PLA scaffold is an innovative tool for cell proliferation and motor neuron differentiation. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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14 pages, 3343 KiB  
Article
Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride
by Giovanni Falcone, Juan P. Real, Santiago D. Palma, Rita P. Aquino, Pasquale Del Gaudio, Emilia Garofalo and Paola Russo
Int. J. Mol. Sci. 2022, 23(3), 1280; https://doi.org/10.3390/ijms23031280 - 24 Jan 2022
Cited by 13 | Viewed by 3667
Abstract
At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of [...] Read more.
At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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17 pages, 9142 KiB  
Article
Biodegradable Poly-ε-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves
by Georg Lutter, Thomas Puehler, Lukas Cyganek, Jette Seiler, Anita Rogler, Tanja Herberth, Philipp Knueppel, Stanislav N. Gorb, Janarthanan Sathananthan, Stephanie Sellers, Oliver J. Müller, Derk Frank and Irma Haben
Int. J. Mol. Sci. 2022, 23(1), 527; https://doi.org/10.3390/ijms23010527 - 4 Jan 2022
Cited by 12 | Viewed by 2640
Abstract
Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. [...] Read more.
Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young’s modulus and mean elongation at Fmax of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 ± 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 ± 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of Fmax (ECFCs: 0.6 ± 0.1 N; iMSCs: 0.7 ± 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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18 pages, 4184 KiB  
Article
Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform
by Dongwei Wu, Johanna Berg, Birte Arlt, Viola Röhrs, Munir A. Al-Zeer, Hedwig E. Deubzer and Jens Kurreck
Int. J. Mol. Sci. 2022, 23(1), 122; https://doi.org/10.3390/ijms23010122 - 23 Dec 2021
Cited by 18 | Viewed by 5592
Abstract
Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance [...] Read more.
Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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14 pages, 3398 KiB  
Article
3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells
by Yuejiao Yang, Apoorv Kulkarni, Gian Domenico Soraru, Joshua M. Pearce and Antonella Motta
Int. J. Mol. Sci. 2021, 22(24), 13676; https://doi.org/10.3390/ijms222413676 - 20 Dec 2021
Cited by 13 | Viewed by 4535
Abstract
Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. [...] Read more.
Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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23 pages, 85975 KiB  
Article
3D Bio-Printability of Hybrid Pre-Crosslinked Hydrogels
by Cartwright Nelson, Slesha Tuladhar, Loren Launen and Ahasan Habib
Int. J. Mol. Sci. 2021, 22(24), 13481; https://doi.org/10.3390/ijms222413481 - 15 Dec 2021
Cited by 20 | Viewed by 4265
Abstract
Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing [...] Read more.
Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing shape fidelity of the scaffolds, various percentages of Carboxymethyl Cellulose (CMC) (viscosity enhancer) and different calcium salts (CaCl2 and CaSO4, physical cross-linkers) were mixed into alginate before extrusion to realize shape fidelity. The overall solid content of Alginate-Carboxymethyl Cellulose (CMC) was limited to 6%. A set of rheological tests, e.g., flow curves, amplitude tests, and three interval thixotropic tests, were performed to identify and compare the shear-thinning capacity, gelation points, and recovery rate of various compositions. The geometrical fidelity of the fabricated scaffolds was defined by printability and collapse tests. The effect of using multiple cross-linkers simultaneously was assessed. Various large-scale scaffolds were fabricated (up to 5.0 cm) using a pre-crosslinked hybrid. Scaffolds were assessed for the ability to support the growth of Escherichia coli using the Most Probable Number technique to quantify bacteria immediately after inoculation and 24 h later. This pre-crosslinking-based rheological property controlling technique can open a new avenue for 3D bio-fabrication of scaffolds, ensuring proper geometry. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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16 pages, 3528 KiB  
Article
Biological and Corrosion Evaluation of In Situ Alloyed NiTi Fabricated through Laser Powder Bed Fusion (LPBF)
by Agnieszka Chmielewska, Anna Dobkowska, Ewa Kijeńska-Gawrońska, Michał Jakubczak, Agnieszka Krawczyńska, Emilia Choińska, Agnieszka Jastrzębska, David Dean, Bartłomiej Wysocki and Wojciech Święszkowski
Int. J. Mol. Sci. 2021, 22(24), 13209; https://doi.org/10.3390/ijms222413209 - 8 Dec 2021
Cited by 7 | Viewed by 2868
Abstract
In this work, NiTi alloy parts were fabricated using laser powder bed fusion (LBPF) from pre-alloyed NiTi powder and in situ alloyed pure Ni and Ti powders. Comparative research on the corrosive and biological properties of both studied materials was performed. Electrochemical corrosion [...] Read more.
In this work, NiTi alloy parts were fabricated using laser powder bed fusion (LBPF) from pre-alloyed NiTi powder and in situ alloyed pure Ni and Ti powders. Comparative research on the corrosive and biological properties of both studied materials was performed. Electrochemical corrosion tests were carried out in phosphate buffered saline at 37 °C, and the degradation rate of the materials was described based on Ni ion release measurements. Cytotoxicity, bacterial growth, and adhesion to the surface of the fabricated coupons were evaluated using L929 cells and spherical Escherichia coli (E. coli) bacteria, respectively. The in situ alloyed NiTi parts exhibit slightly lower corrosion resistance in phosphate buffered saline solution than pre-alloyed NiTi. Moreover, the passive layer formed on in situ alloyed NiTi is weaker than the one formed on the NiTi fabricated from pre-alloyed NiTi powder. Furthermore, in situ alloyed NiTi and NiTi made from pre-alloyed powders have comparable cytotoxicity and biological properties. Overall, the research has shown that nitinol sintered using in situ alloyed pure Ni and Ti is potentially useful for biomedical applications. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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16 pages, 2009 KiB  
Article
Evaluation of the Usability of a Low-Cost 3D Printer in a Tissue Engineering Approach for External Ear Reconstruction
by Constanze Kuhlmann, Jana C. Blum, Thilo L. Schenck, Riccardo E. Giunta and Paul Severin Wiggenhauser
Int. J. Mol. Sci. 2021, 22(21), 11667; https://doi.org/10.3390/ijms222111667 - 28 Oct 2021
Cited by 8 | Viewed by 2980
Abstract
The use of alloplastic materials instead of autologous cartilage grafts offers a new perspective in craniofacial reconstructive surgery. Particularly for regenerative approaches, customized implants enable the surgeon to restore the cartilaginous framework of the ear without donor site morbidity. However, high development and [...] Read more.
The use of alloplastic materials instead of autologous cartilage grafts offers a new perspective in craniofacial reconstructive surgery. Particularly for regenerative approaches, customized implants enable the surgeon to restore the cartilaginous framework of the ear without donor site morbidity. However, high development and production costs of commercially available implants impede clinical translation. For this reason, the usability of a low-cost 3D printer (Ultimaker 2+) as an inhouse-production tool for cheap surgical implants was investigated. The open software architecture of the 3D printer was modified in order to enable printing of biocompatible and biologically degradable polycaprolactone (PCL). Firstly, the printing accuracy and limitations of a PCL implant were compared to reference materials acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). Then the self-made PCL-scaffold was seeded with adipose-tissue derived stem cells (ASCs), and biocompatibility was compared to a commercially available PCL-scaffold using a cell viability staining (FDA/PI) and a dsDNA quantification assay (PicoGreen). Secondly, porous and solid patient-customized ear constructs were manufactured from mirrored CT-imagining data using a computer-assisted design (CAD) and computer-assisted manufacturing (CAM) approach to evaluate printing accuracy and reproducibility. The results show that printing of a porous PCL scaffolds was possible, with an accuracy equivalent to the reference materials at an edge length of 10 mm and a pore size of 0.67 mm. Cell viability, adhesion, and proliferation of the ASCs were equivalent on self-made and the commercially available PCL-scaffolds. Patient-customized ear constructs could be produced well in solid form and with limited accuracy in porous form from all three thermoplastic materials. Printing dimensions and quality of the modified low-cost 3D printer are sufficient for selected tissue engineering applications, and the manufacturing of personalized ear models for surgical simulation at manufacturing costs of EUR 0.04 per cell culture scaffold and EUR 0.90 (0.56) per solid (porous) ear construct made from PCL. Therefore, in-house production of PCL-based tissue engineering scaffolds and surgical implants should be further investigated to facilitate the use of new materials and 3D printing in daily clinical routine. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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21 pages, 8982 KiB  
Article
Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering
by Dong Jin Choi, Kyoung Choi, Sang Jun Park, Young-Jin Kim, Seok Chung and Chun-Ho Kim
Int. J. Mol. Sci. 2021, 22(21), 11600; https://doi.org/10.3390/ijms222111600 - 27 Oct 2021
Cited by 6 | Viewed by 3284
Abstract
Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and [...] Read more.
Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (−10 °C cryogenic plate, 40–80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts’ proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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13 pages, 4445 KiB  
Article
Bioprinting of Cartilage with Bioink Based on High-Concentration Collagen and Chondrocytes
by Evgeny E. Beketov, Elena V. Isaeva, Nina D. Yakovleva, Grigory A. Demyashkin, Nadezhda V. Arguchinskaya, Anastas A. Kisel, Tatiana S. Lagoda, Egor P. Malakhov, Valentin I. Kharlov, Egor O. Osidak, Sergey P. Domogatsky, Sergey A. Ivanov, Petr V. Shegay and Andrey D. Kaprin
Int. J. Mol. Sci. 2021, 22(21), 11351; https://doi.org/10.3390/ijms222111351 - 21 Oct 2021
Cited by 24 | Viewed by 2875
Abstract
The study was aimed at the applicability of a bioink based on 4% collagen and chondrocytes for de novo cartilage formation. Extrusion-based bioprinting was used for the biofabrication. The printing parameters were tuned to obtain stable material flow. In vivo data proved the [...] Read more.
The study was aimed at the applicability of a bioink based on 4% collagen and chondrocytes for de novo cartilage formation. Extrusion-based bioprinting was used for the biofabrication. The printing parameters were tuned to obtain stable material flow. In vivo data proved the ability of the tested bioink to form a cartilage within five to six weeks after the subcutaneous scaffold implantation. Certain areas of cartilage formation were detected as early as in one week. The resulting cartilage tissue had a distinctive structure with groups of isogenic cells as well as a high content of glycosaminoglycans and type II collagen. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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10 pages, 1894 KiB  
Article
Bone Fracture-Treatment Method: Fixing 3D-Printed Polycaprolactone Scaffolds with Hydrogel Type Bone-Derived Extracellular Matrix and β-Tricalcium Phosphate as an Osteogenic Promoter
by Seokhwan Yun, Dami Choi, Dong-Jin Choi, Songwan Jin, Won-Soo Yun, Jung-Bo Huh and Jin-Hyung Shim
Int. J. Mol. Sci. 2021, 22(16), 9084; https://doi.org/10.3390/ijms22169084 - 23 Aug 2021
Cited by 14 | Viewed by 2622
Abstract
Bone formation and growth are crucial for treating bone fractures. Improving bone-reconstruction methods using autologous bone and synthetic implants can reduce the recovery time. Here, we investigated three treatments using two different materials, a bone-derived decellularized extracellular matrix (bdECM) and β-tricalcium phosphate (β-TCP), [...] Read more.
Bone formation and growth are crucial for treating bone fractures. Improving bone-reconstruction methods using autologous bone and synthetic implants can reduce the recovery time. Here, we investigated three treatments using two different materials, a bone-derived decellularized extracellular matrix (bdECM) and β-tricalcium phosphate (β-TCP), individually and in combination, as osteogenic promoter between bone and 3D-printed polycaprolactone scaffold (6-mm diameter) in rat calvarial defects (8-mm critical diameter). The materials were tested with a human pre-osteoblast cell line (MG63) to determine the effects of the osteogenic promoter on bone formation in vitro. A polycaprolactone (PCL) scaffold with a porous structure was placed at the center of the in vivo rat calvarial defects. The gap between the defective bone and PCL scaffold was filled with each material. Animals were sacrificed four weeks post-implantation, and skull samples were preserved for analysis. The preserved samples were scanned by micro-computed tomography and analyzed histologically to examine the clinical benefits of the materials. The bdECM–β-TCP mixture showed faster bone formation and a lower inflammatory response in the rats. Therefore, our results imply that a bdECM–β-TCP mixture is an ideal osteogenic promoter for treating fractures. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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19 pages, 1974 KiB  
Article
Quantitative Assessment of Point-of-Care 3D-Printed Patient-Specific Polyetheretherketone (PEEK) Cranial Implants
by Neha Sharma, Soheila Aghlmandi, Federico Dalcanale, Daniel Seiler, Hans-Florian Zeilhofer, Philipp Honigmann and Florian M. Thieringer
Int. J. Mol. Sci. 2021, 22(16), 8521; https://doi.org/10.3390/ijms22168521 - 7 Aug 2021
Cited by 49 | Viewed by 5873
Abstract
Recent advancements in medical imaging, virtual surgical planning (VSP), and three-dimensional (3D) printing have potentially changed how today’s craniomaxillofacial surgeons use patient information for customized treatments. Over the years, polyetheretherketone (PEEK) has emerged as the biomaterial of choice to reconstruct craniofacial defects. With [...] Read more.
Recent advancements in medical imaging, virtual surgical planning (VSP), and three-dimensional (3D) printing have potentially changed how today’s craniomaxillofacial surgeons use patient information for customized treatments. Over the years, polyetheretherketone (PEEK) has emerged as the biomaterial of choice to reconstruct craniofacial defects. With advancements in additive manufacturing (AM) systems, prospects for the point-of-care (POC) 3D printing of PEEK patient-specific implants (PSIs) have emerged. Consequently, investigating the clinical reliability of POC-manufactured PEEK implants has become a necessary endeavor. Therefore, this paper aims to provide a quantitative assessment of POC-manufactured, 3D-printed PEEK PSIs for cranial reconstruction through characterization of the geometrical, morphological, and biomechanical aspects of the in-hospital 3D-printed PEEK cranial implants. The study results revealed that the printed customized cranial implants had high dimensional accuracy and repeatability, displaying clinically acceptable morphologic similarity concerning fit and contours continuity. From a biomechanical standpoint, it was noticed that the tested implants had variable peak load values with discrete fracture patterns and failed at a mean (SD) peak load of 798.38 ± 211.45 N. In conclusion, the results of this preclinical study are in line with cranial implant expectations; however, specific attributes have scope for further improvements. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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10 pages, 2079 KiB  
Article
3D-Printed Collagen-Based Waveform Microfibrous Scaffold for Periodontal Ligament Reconstruction
by Hsu-Hsiang Lin, Pen-Hsiu Grace Chao, Wei-Chiu Tai and Po-Chun Chang
Int. J. Mol. Sci. 2021, 22(14), 7725; https://doi.org/10.3390/ijms22147725 - 20 Jul 2021
Cited by 15 | Viewed by 4017
Abstract
Reconstruction of the periodontal ligament (PDL) to fulfill functional requirement remains a challenge. This study sought to develop a biomimetic microfibrous system capable of withstanding the functional load to assist PDL regeneration. Collagen-based straight and waveform microfibers to guide PDL cell growth were [...] Read more.
Reconstruction of the periodontal ligament (PDL) to fulfill functional requirement remains a challenge. This study sought to develop a biomimetic microfibrous system capable of withstanding the functional load to assist PDL regeneration. Collagen-based straight and waveform microfibers to guide PDL cell growth were prepared using an extrusion-based bioprinter, and a laminar flow-based bioreactor was used to generate fluidic shear stress. PDL cells were seeded on the respective microfibers with 0 or 6 dynes/cm2 fluidic shear stress for 1–4 h. The viability, morphology, adhesion pattern, and gene expression levels of PDL cells were assessed. The results revealed that upon bioprinting optimization, collagen-based microfibers were successfully fabricated. The straight microfibers were 189.9 ± 11.44 μm wide and the waveform microfibers were 235.9 ± 11.22 μm wide. Under 6 dynes/cm2 shear stress, PDL cells were successfully seeded, and cytoskeleton expansion, adhesion, and viability were greater. Cyclin D, E-cadherin, and periostin were upregulated on the waveform microfibers. In conclusion, 3D-printed collagen-based waveform microfibers preserved PDL cell viability and exhibited an enhanced tendency to promote healing and regeneration under shear stress. This approach is promising for the development of a guiding scaffold for PDL regeneration. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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19 pages, 9879 KiB  
Article
Biocompatibility and Biological Performance Evaluation of Additive-Manufactured Bioabsorbable Iron-Based Porous Suture Anchor in a Rabbit Model
by Chien-Cheng Tai, Hon-Lok Lo, Chen-Kun Liaw, Yu-Min Huang, Yen-Hua Huang, Kuo-Yi Yang, Chih-Chieh Huang, Shin-I Huang, Hsin-Hsin Shen, Tzu-Hung Lin, Chun-Kuan Lu, Wen-Chih Liu, Jui-Sheng Sun, Pei-I Tsai and Chih-Yu Chen
Int. J. Mol. Sci. 2021, 22(14), 7368; https://doi.org/10.3390/ijms22147368 - 8 Jul 2021
Cited by 9 | Viewed by 3433
Abstract
This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in [...] Read more.
This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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Jump to: Research

46 pages, 3118 KiB  
Review
A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications
by Maria C. Teixeira, Nicole S. Lameirinhas, João P. F. Carvalho, Armando J. D. Silvestre, Carla Vilela and Carmen S. R. Freire
Int. J. Mol. Sci. 2022, 23(12), 6564; https://doi.org/10.3390/ijms23126564 - 12 Jun 2022
Cited by 42 | Viewed by 6008
Abstract
Three-dimensional (3D) bioprinting is an innovative technology in the biomedical field, allowing the fabrication of living constructs through an approach of layer-by-layer deposition of cell-laden inks, the so-called bioinks. An ideal bioink should possess proper mechanical, rheological, chemical, and biological characteristics to ensure [...] Read more.
Three-dimensional (3D) bioprinting is an innovative technology in the biomedical field, allowing the fabrication of living constructs through an approach of layer-by-layer deposition of cell-laden inks, the so-called bioinks. An ideal bioink should possess proper mechanical, rheological, chemical, and biological characteristics to ensure high cell viability and the production of tissue constructs with dimensional stability and shape fidelity. Among the several types of bioinks, hydrogels are extremely appealing as they have many similarities with the extracellular matrix, providing a highly hydrated environment for cell proliferation and tunability in terms of mechanical and rheological properties. Hydrogels derived from natural polymers, and polysaccharides, in particular, are an excellent platform to mimic the extracellular matrix, given their low cytotoxicity, high hydrophilicity, and diversity of structures. In fact, polysaccharide-based hydrogels are trendy materials for 3D bioprinting since they are abundant and combine adequate physicochemical and biomimetic features for the development of novel bioinks. Thus, this review portrays the most relevant advances in polysaccharide-based hydrogel bioinks for 3D bioprinting, focusing on the last five years, with emphasis on their properties, advantages, and limitations, considering polysaccharide families classified according to their source, namely from seaweed, higher plants, microbial, and animal (particularly crustaceans) origin. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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15 pages, 3249 KiB  
Review
Application of 3D-Printed, PLGA-Based Scaffolds in Bone Tissue Engineering
by Fengbo Sun, Xiaodan Sun, Hetong Wang, Chunxu Li, Yu Zhao, Jingjing Tian and Yuanhua Lin
Int. J. Mol. Sci. 2022, 23(10), 5831; https://doi.org/10.3390/ijms23105831 - 23 May 2022
Cited by 35 | Viewed by 5161
Abstract
Polylactic acid–glycolic acid (PLGA) has been widely used in bone tissue engineering due to its favorable biocompatibility and adjustable biodegradation. 3D printing technology can prepare scaffolds with rich structure and function, and is one of the best methods to obtain scaffolds for bone [...] Read more.
Polylactic acid–glycolic acid (PLGA) has been widely used in bone tissue engineering due to its favorable biocompatibility and adjustable biodegradation. 3D printing technology can prepare scaffolds with rich structure and function, and is one of the best methods to obtain scaffolds for bone tissue repair. This review systematically summarizes the research progress of 3D-printed, PLGA-based scaffolds. The properties of the modified components of scaffolds are introduced in detail. The influence of structure and printing method change in printing process is analyzed. The advantages and disadvantages of their applications are illustrated by several examples. Finally, we briefly discuss the limitations and future development direction of current 3D-printed, PLGA-based materials for bone tissue repair. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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25 pages, 1447 KiB  
Review
Active Materials for 3D Printing in Small Animals: Current Modalities and Future Directions for Orthopedic Applications
by Parastoo Memarian, Elham Pishavar, Federica Zanotti, Martina Trentini, Francesca Camponogara, Elisa Soliani, Paolo Gargiulo, Maurizio Isola and Barbara Zavan
Int. J. Mol. Sci. 2022, 23(3), 1045; https://doi.org/10.3390/ijms23031045 - 18 Jan 2022
Cited by 17 | Viewed by 5021
Abstract
The successful clinical application of bone tissue engineering requires customized implants based on the receiver’s bone anatomy and defect characteristics. Three-dimensional (3D) printing in small animal orthopedics has recently emerged as a valuable approach in fabricating individualized implants for receiver-specific needs. In veterinary [...] Read more.
The successful clinical application of bone tissue engineering requires customized implants based on the receiver’s bone anatomy and defect characteristics. Three-dimensional (3D) printing in small animal orthopedics has recently emerged as a valuable approach in fabricating individualized implants for receiver-specific needs. In veterinary medicine, because of the wide range of dimensions and anatomical variances, receiver-specific diagnosis and therapy are even more critical. The ability to generate 3D anatomical models and customize orthopedic instruments, implants, and scaffolds are advantages of 3D printing in small animal orthopedics. Furthermore, this technology provides veterinary medicine with a powerful tool that improves performance, precision, and cost-effectiveness. Nonetheless, the individualized 3D-printed implants have benefited several complex orthopedic procedures in small animals, including joint replacement surgeries, critical size bone defects, tibial tuberosity advancement, patellar groove replacement, limb-sparing surgeries, and other complex orthopedic procedures. The main purpose of this review is to discuss the application of 3D printing in small animal orthopedics based on already published papers as well as the techniques and materials used to fabricate 3D-printed objects. Finally, the advantages, current limitations, and future directions of 3D printing in small animal orthopedics have been addressed. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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19 pages, 1285 KiB  
Review
Tissue Engineered Transcatheter Pulmonary Valved Stent Implantation: Current State and Future Prospect
by Xiling Zhang, Thomas Puehler, Jette Seiler, Stanislav N. Gorb, Janarthanan Sathananthan, Stephanie Sellers, Assad Haneya, Jan-Hinnerk Hansen, Anselm Uebing, Oliver J. Müller, Derk Frank and Georg Lutter
Int. J. Mol. Sci. 2022, 23(2), 723; https://doi.org/10.3390/ijms23020723 - 10 Jan 2022
Cited by 5 | Viewed by 2763
Abstract
Patients with the complex congenital heart disease (CHD) are usually associated with right ventricular outflow tract dysfunction and typically require multiple surgical interventions during their lives to relieve the right ventricular outflow tract abnormality. Transcatheter pulmonary valve replacement was used as a non-surgical, [...] Read more.
Patients with the complex congenital heart disease (CHD) are usually associated with right ventricular outflow tract dysfunction and typically require multiple surgical interventions during their lives to relieve the right ventricular outflow tract abnormality. Transcatheter pulmonary valve replacement was used as a non-surgical, less invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly developing over the past years. Despite the current favorable results of transcatheter pulmonary valve replacement, many patients eligible for pulmonary valve replacement are still not candidates for transcatheter pulmonary valve replacement. Therefore, one of the significant future challenges is to expand transcatheter pulmonary valve replacement to a broader patient population. This review describes the limitations and problems of existing techniques and focuses on decellularized tissue engineering for pulmonary valve stenting. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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30 pages, 5757 KiB  
Review
3D Printed Multiphasic Scaffolds for Osteochondral Repair: Challenges and Opportunities
by Stephanie E. Doyle, Finn Snow, Serena Duchi, Cathal D. O’Connell, Carmine Onofrillo, Claudia Di Bella and Elena Pirogova
Int. J. Mol. Sci. 2021, 22(22), 12420; https://doi.org/10.3390/ijms222212420 - 17 Nov 2021
Cited by 20 | Viewed by 4712
Abstract
Osteochondral (OC) defects are debilitating joint injuries characterized by the loss of full thickness articular cartilage along with the underlying calcified cartilage through to the subchondral bone. While current surgical treatments can provide some relief from pain, none can fully repair all the [...] Read more.
Osteochondral (OC) defects are debilitating joint injuries characterized by the loss of full thickness articular cartilage along with the underlying calcified cartilage through to the subchondral bone. While current surgical treatments can provide some relief from pain, none can fully repair all the components of the OC unit and restore its native function. Engineering OC tissue is challenging due to the presence of the three distinct tissue regions. Recent advances in additive manufacturing provide unprecedented control over the internal microstructure of bioscaffolds, the patterning of growth factors and the encapsulation of potentially regenerative cells. These developments are ushering in a new paradigm of ‘multiphasic’ scaffold designs in which the optimal micro-environment for each tissue region is individually crafted. Although the adoption of these techniques provides new opportunities in OC research, it also introduces challenges, such as creating tissue interfaces, integrating multiple fabrication techniques and co-culturing different cells within the same construct. This review captures the considerations and capabilities in developing 3D printed OC scaffolds, including materials, fabrication techniques, mechanical function, biological components and design. Full article
(This article belongs to the Special Issue 3D Printing and Biomaterials for Biological and Medical Application)
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