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Biofabrication: From Additive Bio-Manufacturing to Bioprinting

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 69087

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Prof. Dr. Amir A. Zadpoor

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Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft, The Netherlands
Interests: biofabrication and additive bio-manufacturing; mechanobiology; surface bio-functionalization; infection prevention and treatment; metamaterials
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Special Issue Information

Dear Colleagues,

Healthcare is one of the areas that has benefited the most from recent advances in advanced 3D printing (additive manufacturing) techniques. An increasing number of researchers and clinicians are therefore studying the various ways through which 3D printing could be used for advancing biomedical research and improving currently available clinical treatments. This Special Issue aims to present some of the best research currently performed in those directions. The topics of interest include (but are not limited to):

- Additively manufactured (i.e., 3D printed) medical devices including implants, medical instruments, prosthetics, and orthotics
- Tissue and organ printing
- 3D printed drugs and drug delivery systems
- Bioprinting of tissue analogues and disease models
- Additive manufacturing of biomaterials
- Pre- and post-processing of 3D printed medical devices and biomaterials including surface bio-functionalizations and coatings
- Patient-specific solutions enabled by 3D printing
- Hybrid (i.e., combined additive and subtractive) manufacturing, indirect additive manufacturing, and other novel fabrication techniques for biomedical applications.
- Evaluation of the biological and clinical performance of 3D printed biomaterials, tissues, organs, and medical devices.

Prof. Dr. Amir A. Zadpoor
Guest Editor

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Keywords

Bio-printing
3D printing in healthcare
biomaterials
medical devices
regenerative medicine
tissue equivalents and disease models
3D printed drugs

Published Papers (11 papers)

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15 pages, 4820 KiB

Open AccessArticle

A Novel Fabrication Method for Compliant Silicone Phantoms of Arterial Geometry for Use in Particle Image Velocimetry of Haemodynamics

by Sina G. Yazdi, Larissa Huetter, Paul D. Docherty, Petra N. Williamson, Don Clucas, Mark Jermy and Patrick H. Geoghegan

Appl. Sci. 2019, 9(18), 3811; https://doi.org/10.3390/app9183811 - 11 Sep 2019

Cited by 19 | Viewed by 4988

Abstract

Cardiovascular diseases (CVDs) are one of the leading causes of death globally. In-vitro measurement of blood flow in compliant arterial phantoms can provide better insight into haemodynamic states and therapeutic procedures. However, current fabrication techniques are not capable of producing thin-walled compliant phantoms of complex shapes. This study presents a new approach for the fabrication of compliant phantoms suitable for optical measurement. Two 1.5× scaled models of the ascending aorta, including the brachiocephalic artery (BCA), were fabricated from silicone elastomer Sylgard-184. The initial phantom used the existing state of the art lost core manufacturing technique with simple end supports, an acrylonitrile butadiene styrene (ABS) additive manufactured male mould and Ebalta-milled female mould. The second phantom was produced with the same method but used more rigid end supports and ABS male and female moulds. The wall thickness consistency and quality of resulting stereoscopic particle image velocimetry (SPIV) were used to verify the fidelity of the phantom for optical measurement and investigation of physiological flow fields. However, the initial phantom had a rough surface that obscured SPIV analysis and had a variable wall thickness (range = 0.815 mm). The second phantom provided clear particle images and had a less variable wall thickness (range = 0.317 mm). The manufacturing method developed is suitable for fast and cost-effective fabrication of different compliant arterial phantom geometries. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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19 pages, 11500 KiB

Open AccessArticle

Fabrication and Analysis of a Ti6Al4V Implant for Cranial Restoration

by Khaja Moiduddin, Syed Hammad Mian, Usama Umer and Hisham Alkhalefah

Appl. Sci. 2019, 9(12), 2513; https://doi.org/10.3390/app9122513 - 20 Jun 2019

Cited by 23 | Viewed by 5854

Abstract

A custom made implant is critical in cranioplasty to cushion and restore intracranial anatomy, as well as to recover the appearance and attain cognitive stability in the patient. The utilization of customized titanium alloy implants using three-dimensional (3D) reconstruction technique and fabricated using Electron Beam Melting (EBM) has gained significant recognition in recent years, owing to their convenience and effectiveness. Besides, the conventional technique or the extant practice of transforming the standard plates is unreliable, arduous and tedious. As a result, this work aims to produce a customized cranial implant using 3D reconstruction that is reliable in terms of fitting accuracy, appearance, mechanical strength, and consistent material composition. A well-defined methodology initiating from EBM fabrication to final validation has been outlined in this work. The custom design of the implant was carried out by mirror reconstruction of the skull’s defective region, acquired through computer tomography. The design of the customized implant was then analyzed for mechanical stresses by applying finite element analysis. Consequently, the 3D model of the implant was fabricated from Ti6Al4V ELI powder with a thickness of ≃1.76–2 mm. Different tests were employed to evaluate the bio-mechanical stability and strength of the fabricated customized implant design. A 3D comparison study was performed to ensure there was anatomical accuracy, as well as to maintain gratifying aesthetics. The bio-mechanical analysis results revealed that the maximum Von Mises stress (2.5 MPa), strain distribution (1.49 × 10⁻⁴) and deformation (3.26 × 10⁻⁶ mm) were significantly low in magnitude, thus proving the implant load resistance ability. The average yield and tensile strengths for the fabricated Ti6Al4V ELI EBM specimen were found to be 825 MPa and 880 MPa, respectively, which were well over the prescribed strength for Ti6Al4V ELI implant material. The hardness study also resulted in an acceptable outcome within the acceptable range of 30–35 HRC. Certainly, the chemical composition of the fabricated EBM specimen was intact as established in EDX analysis. The weight of the cranial implant (128 grams) was also in agreement with substituted defected bone portion, ruling out any stress shielding effect. With the proposed approach, the anatomy of the cranium deformities can be retrieved effectively and efficiently. The implementation of 3D reconstruction techniques can conveniently reduce tedious alterations in the implant design and subsequent errors. It can be a valuable and reliable approach to enhance implant fitting, stability, and strength. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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9 pages, 1845 KiB

Open AccessArticle

Spatial Modes of Laser-Induced Mass Transfer in Micro-Gaps

by Tobias C. Foertsch, Alex T. Davis, Roman Popov, Clemens von Bojničić-Kninski, Felix E. Held, Svetlana B. Tsogoeva, Felix F. Loeffler and Alexander Nesterov-Mueller

Appl. Sci. 2019, 9(7), 1303; https://doi.org/10.3390/app9071303 - 28 Mar 2019

Cited by 1 | Viewed by 3379

Abstract

We have observed the concentric deposition patterns of small molecules transferred by means of laser-induced forward transfer (LIFT). The patterns comprised different parts whose presence changed with the experimental constraints in a mode-like fashion. In experiments, we studied this previously unknown phenomenon and derived model assumptions for its emergence. We identified aerosol micro-flow and geometric confinement as the mechanism behind the mass transfer and the cause of the concentric patterns. We validated our model using a simulation. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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19 pages, 3366 KiB

Open AccessArticle

Peptide Mediated Antimicrobial Dental Adhesive System

by Sheng-Xue Xie, Kyle Boone, Sarah Kay VanOosten, Esra Yuca, Linyong Song, Xueping Ge, Qiang Ye, Paulette Spencer and Candan Tamerler

Appl. Sci. 2019, 9(3), 557; https://doi.org/10.3390/app9030557 - 08 Feb 2019

Cited by 28 | Viewed by 5271

Abstract

The most common cause for dental composite failures is secondary caries due to invasive bacterial colonization of the adhesive/dentin (a/d) interface. Innate material weakness often lead to an insufficient seal between the adhesive and dentin. Consequently, bacterial by-products invade the porous a/d interface leading to material degradation and dental caries. Current approaches to achieve antibacterial properties in these materials continue to raise concerns regarding hypersensitivity and antibiotic resistance. Herein, we have developed a multi-faceted, bio-functionalized approach to overcome the vulnerability of such interfaces. An antimicrobial adhesive formulation was designed using a combination of antimicrobial peptide and a ε-polylysine resin system. Effector molecules boasting innate immunity are brought together with a biopolymer offering a two-fold biomimetic design approach. The selection of ε-polylysine was inspired due to its non-toxic nature and common use as food preservative. Biomolecular characterization and functional activity of our engineered dental adhesive formulation were assessed and the combinatorial formulation demonstrated significant antimicrobial activity against Streptococcus mutans. Our antimicrobial peptide-hydrophilic adhesive hybrid system design offers advanced, biofunctional properties at the critical a/d interface. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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10 pages, 1321 KiB

Open AccessCommunication

3D Printing of Functional Assemblies with Integrated Polymer-Bonded Magnets Demonstrated with a Prototype of a Rotary Blood Pump

by Kai Von Petersdorff-Campen, Yannick Hauswirth, Julia Carpenter, Andreas Hagmann, Stefan Boës, Marianne Schmid Daners, Dirk Penner and Mirko Meboldt

Appl. Sci. 2018, 8(8), 1275; https://doi.org/10.3390/app8081275 - 01 Aug 2018

Cited by 38 | Viewed by 6651

Abstract

Conventional magnet manufacturing is a significant bottleneck in the development processes of products that use magnets, because every design adaption requires production steps with long lead times. Additive manufacturing of magnetic components delivers the opportunity to shift to agile and test-driven development in early prototyping stages, as well as new possibilities for complex designs. In an effort to simplify integration of magnetic components, the current work presents a method to directly print polymer-bonded hard magnets of arbitrary shape into thermoplastic parts by fused deposition modeling. This method was applied to an early prototype design of a rotary blood pump with magnetic bearing and magnetic drive coupling. Thermoplastics were compounded with 56 vol.% isotropic NdFeB powder to manufacture printable filament. With a powder loading of 56 vol.%, remanences of 350 mT and adequate mechanical flexibility for robust processability were achieved. This compound allowed us to print a prototype of a turbodynamic pump with integrated magnets in the impeller and housing in one piece on a low-cost, end-user 3D printer. Then, the magnetic components in the printed pump were fully magnetized in a pulsed Bitter coil. The pump impeller is driven by magnetic coupling to non-printed permanent magnets rotated by a brushless DC motor, resulting in a flow rate of 3 L/min at 1000 rpm. For the first time, an application of combined multi-material and magnet printing by fused deposition modeling was shown. The presented process significantly simplifies the prototyping of products that use magnets, such as rotary blood pumps, and opens the door for more complex and innovative designs. It will also help postpone the shift to conventional manufacturing methods to later phases of the development process. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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16 pages, 3945 KiB

Open AccessArticle

Printability Study of Bioprinted Tubular Structures Using Liquid Hydrogel Precursors in a Support Bath

by Houzhu Ding and Robert C. Chang

Appl. Sci. 2018, 8(3), 403; https://doi.org/10.3390/app8030403 - 09 Mar 2018

Cited by 80 | Viewed by 7348

Abstract

Microextrusion-based bioprinting within a support bath material is an emerging additive manufacturing paradigm for complex three-dimensional (3D) tissue construct fabrication. Although a support bath medium enables arbitrary in-process geometries to be printed, a significant challenge lies in preserving the shape fidelity upon the extraction of the support bath material. Based on the bioprinting in a support bath paradigm, this paper advances quantitative analyses to systematically determine the printability of cell-laden liquid hydrogel precursors towards filament-based tissue constructs. First, a yield stress nanoclay material is judiciously selected as the support bath medium owing to its insensitivity to temperature and ionic variations that are considered in the context of the current gelatin-alginate bio-ink material formulation. Furthermore, phenomenological observations for the rheology-mediated print outcomes enable the compositions for the bio-ink material (10% gelatin, 3% alginate), in tandem with the support bath medium (4% nanoclay, 0.5% CaCl₂), to be identified. To systematically evaluate the performance outcomes for bioprinting within a support bath, this paper advances an experimental parametric study to optimize the 3D structural shape fidelity by varying parameters such as the layer height, extrusion flowrate, printing temperature, and printhead speed, towards fabricating complex 3D structures with the stabilization of the desired shape outcome. Specifically, it is found that the layer height and printhead speed are determinant parameters for the extent of successive layer fusion. Moreover, maintenance of an optimal bath temperature is identified as a key parameter for establishing the printability for the hydrogel bio-ink. Studying this effect is enabled by the custom design of a PID temperature control system with integration with the bioprinter for real-time precision control of the support bath temperature. In order to qualify the printed construct, a surface irregularity metric, defined as the average height difference between consecutive local maximum and minimum points of the binary image contour for the printed structure, is advanced to evaluate the quality of the printed constructs. Complex one-to-four bifurcating tubular structure prints demonstrate the applicability of the optimized bioprinting parameter space to create exemplar 3D human vessel-like structures. Finally, a cell viability assay and perfusion test for a printed cell-laden tubular element demonstrates high cell survival rates and leakage-free flow, respectively. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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16 pages, 6660 KiB

Open AccessArticle

A Biomimetic Approach for Designing a Full External Breast Prosthesis: Post-Mastectomy

by Pedro Cruz, F. Josue Hernandez, Ma. Lourdes Zuñiga, Jose Maria Rodríguez, Rafael Figueroa, Antonio Vertiz and Zaira Pineda

Appl. Sci. 2018, 8(3), 357; https://doi.org/10.3390/app8030357 - 01 Mar 2018

Cited by 5 | Viewed by 8198

Abstract

This work presents the design of a new breast prosthesis using the biomimetic technique for cases of complete mastectomy to address the problem of the increasing number of women diagnosed with breast cancer in Mexico who are candidates for a mastectomy. The designed prosthesis considers the morphology of a real breast regarding its internal structure to obtain authentic mobility and feel. In order to accomplish this, a model was obtained in 3D CAD using a coordinate measuring machine (CMM) that can be scalable without losing its qualities, and which can be used in any type of patient; afterwards, a finite element model was developed and a static analysis performed with suggested load cases to evaluate the sensitivity and naturalness of the prosthesis; and finally, a modal analysis was conducted. The results obtained in displacements and in distribution of stress for the load cases assessed are consistent with those of a real breast: there were smooth contours and there was natural mobility in the prosthesis designed by means of the biomimetic technique. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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2540 KiB

Open AccessArticle

A Bibliometric Study to Assess Bioprinting Evolution

by Adrien Naveau, Rawen Smirani, Sylvain Catros, Hugo De Oliveira, Jean-Christophe Fricain and Raphael Devillard

Appl. Sci. 2017, 7(12), 1331; https://doi.org/10.3390/app7121331 - 20 Dec 2017

Cited by 21 | Viewed by 6322

Abstract

Bioprinting as a tissue engineering tool is one of the most promising technologies for overcoming organ shortage. However, the spread of populist articles among on this technology could potentially lead public opinion to idealize its readiness. This bibliometric study aimed to trace the evolution of bioprinting literature over the past decade (i.e., 2000 to 2015) using the SCI-expanded database of Web of Science^® (WoS, Thomson Reuters). The articles were analyzed by combining various bibliometric tools, such as science mapping and topic analysis, and a Technology Readiness Scale was adapted to assess the evolution of this emerging field. The number of analyzed publications was low (231), but the literature grew exceptionally fast. The “Engineering, Biomedical” was still the most represented WoS category. Some of the recent fronts were “hydrogels” and “stem cells”, while “in vitro” remained one of the most used keywords. The number of countries and journals involved in bioprinting literature grew substantially in one decade, also supporting the idea of an increasing community. Neither the United States’ leadership in bioprinting productivity nor the role of universities in publications were challenged. “Biofabrication” and “Biomaterials” journals were still the leaders of the bioprinting field. Bioprinting is a young but promising technology. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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Review

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24 pages, 3885 KiB

Open AccessFeature PaperReview

Biomimicry in Bio-Manufacturing: Developments in Melt Electrospinning Writing Technology Towards Hybrid Biomanufacturing

by Ferdows Afghah, Caner Dikyol, Mine Altunbek and Bahattin Koc

Appl. Sci. 2019, 9(17), 3540; https://doi.org/10.3390/app9173540 - 28 Aug 2019

Cited by 39 | Viewed by 9046

Abstract

Melt electrospinning writing has been emerged as a promising technique in the field of tissue engineering, with the capability of fabricating controllable and highly ordered complex three-dimensional geometries from a wide range of polymers. This three-dimensional (3D) printing method can be used to fabricate scaffolds biomimicking extracellular matrix of replaced tissue with the required mechanical properties. However, controlled and homogeneous cell attachment on melt electrospun fibers is a challenge. The combination of melt electrospinning writing with other tissue engineering approaches, called hybrid biomanufacturing, has introduced new perspectives and increased its potential applications in tissue engineering. In this review, principles and key parameters, challenges, and opportunities of melt electrospinning writing, and particularly, recent approaches and materials in this field are introduced. Subsequently, hybrid biomanufacturing strategies are presented for improved biological and mechanical properties of the manufactured porous structures. An overview of the possible hybrid setups and applications, future perspective of hybrid processes, guidelines, and opportunities in different areas of tissue/organ engineering are also highlighted. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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15 pages, 1991 KiB

Open AccessReview

Acellular Small-Diameter Tissue-Engineered Vascular Grafts

by Zhen Li, Xinda Li, Tao Xu and Lei Zhang

Appl. Sci. 2019, 9(14), 2864; https://doi.org/10.3390/app9142864 - 18 Jul 2019

Cited by 13 | Viewed by 4013

Abstract

Tissue-engineered vascular grafts (TEVGs) are considered one of the most effective means of fabricating vascular grafts. However, for small-diameter TEVGs, there are ongoing issues regarding long-term patency and limitations related to long-term in vitro culture and immune reactions. The use of acellular TEVG is a more convincing method, which can achieve in situ blood vessel regeneration and better meet clinical needs. This review focuses on the current state of acellular TEVGs based on scaffolds and gives a summary of the methodologies and in vitro/in vivo test results related to acellular TEVGs obtained in recent years. Various strategies for improving the properties of acellular TEVGs are also discussed. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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Other

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900 KiB

Open AccessFeature PaperPerspective

Fabricating High-Quality 3D-Printed Alloys for Dental Applications

by Min-Ho Hong, Bong Ki Min and Tea-Yub Kwon

Appl. Sci. 2017, 7(7), 710; https://doi.org/10.3390/app7070710 - 10 Jul 2017

Cited by 10 | Viewed by 6600

Abstract

Metal additive manufacturing (AM), especially selective laser melting (SLM), has been receiving particular attention because metallic functional structures with complicated configurations can be effectively fabricated using the technique. However, there still exist some future challenges for the fabrication of high-quality SLM products for dental applications. First, the surface quality of SLM products should be further improved by standardizing the laser process parameters or by appropriately post-treating the surface. Second, it should be guaranteed that dental SLM restorations have good dimensional accuracy and, in particular, a good marginal fit. Third, a definitive standard regarding building and scanning strategies, which affect the anisotropy, should be established to optimize the mechanical properties and fatigue resistance of SLM dental structures. Fourth, the SLM substructure’s bonding and support to veneering ceramic should be further studied to facilitate the use of esthetic dental restorations. Finally, the biocompatibility of SLM dental alloys should be carefully examined and improved to minimize the potential release of toxic metal ions from the alloys. Future research of SLM should focus on solving the above challenges, as well as on fabricating dental structures with “controlled” porosity. Full article

(This article belongs to the Special Issue Biofabrication: From Additive Bio-Manufacturing to Bioprinting)

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