3D Printing for Tissue Engineering and Regenerative Medicine

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B:Biology and Biomedicine".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 53820

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Guest Editor
Departments of Biomedical Engineering and Pediatrics, Georgia Institute of Technology & Emory University School of Medicine, Atlanta, GA 30332, USA
Interests: biomanufacturing; 3D bioprinting; cardiovascular tissue engineering; nano-biomaterials
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Special Issue Information

Dear colleagues,

Three-dimensional (3D) printing enables the fabrication of tissue-engineered constructs and devices from a patient’s own medical data, leading to creation of anatomically-matched and patient-specific constructs. There is a growing interest in applying 3D printing technologies in the fields of tissue engineering and regenerative medicine. The main printing methods include extrusion-based, vat photopolymerization, droplet-based, and powder-based printing. A variety of materials have been used for printing, from metal alloys and ceramics to polymers, elastomers, and hydrogels to extracellular matrix proteins. More recently, bioprinting, a subcategory of 3D printing, has enabled the precise assembly of cell-laden biomaterials (i.e., bio-inks) for the construction of complex 3D functional living tissues or artificial organs.

In this Special Issue, we aim to capture state-of-the-art research papers and the most current review papers focusing on 3D printing for tissue engineering and regenerative medicine. In particular, we seek novel studies on the development of 3D printing and bioprinting approaches, developing printable materials (inks and bio-inks), and utilizing 3D-printed scaffolds for tissue engineering and regenerative medicine applications. These applications are not limited to but include scaffolds for in vivo tissue regeneration and tissue analogues for in vitro disease modeling and/or drug screening.

Dr. Murat Guvendiren
Dr. Vahid Serpooshan
Guest Editors

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Keywords

  • Additive manufacturing
  • 3D printing
  • 3D bioprinting
  • Biofabrication
  • Bio-ink
  • Tissue engineering
  • Regenerative medicine
  • Microfabrication technologies
  • Scaffold design

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Published Papers (9 papers)

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Editorial

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4 pages, 184 KiB  
Editorial
Editorial for the Special Issue on 3D Printing for Tissue Engineering and Regenerative Medicine
by Vahid Serpooshan and Murat Guvendiren
Micromachines 2020, 11(4), 366; https://doi.org/10.3390/mi11040366 - 31 Mar 2020
Cited by 11 | Viewed by 2503
Abstract
Three-dimensional (3D) bioprinting uses additive manufacturing techniques to fabricate 3D structures consisting of heterogenous selections of living cells, biomaterials, and active biomolecules [...] Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)

Research

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12 pages, 2583 KiB  
Article
The Influence of Electron Beam Sterilization on In Vivo Degradation of β-TCP/PCL of Different Composite Ratios for Bone Tissue Engineering
by Jin-Ho Kang, Janelle Kaneda, Jae-Gon Jang, Kumaresan Sakthiabirami, Elaine Lui, Carolyn Kim, Aijun Wang, Sang-Won Park and Yunzhi Peter Yang
Micromachines 2020, 11(3), 273; https://doi.org/10.3390/mi11030273 - 6 Mar 2020
Cited by 9 | Viewed by 5192
Abstract
We evaluated the effect of electron beam (E-beam) sterilization (25 kGy, ISO 11137) on the degradation of β-tricalcium phosphate/polycaprolactone (β-TCP/PCL) composite filaments of various ratios (0:100, 20:80, 40:60, and 60:40 TCP:PCL by mass) in a rat subcutaneous model for 24 weeks. Volumes of [...] Read more.
We evaluated the effect of electron beam (E-beam) sterilization (25 kGy, ISO 11137) on the degradation of β-tricalcium phosphate/polycaprolactone (β-TCP/PCL) composite filaments of various ratios (0:100, 20:80, 40:60, and 60:40 TCP:PCL by mass) in a rat subcutaneous model for 24 weeks. Volumes of the samples before implantation and after explantation were measured using micro-computed tomography (micro-CT). The filament volume changes before sacrifice were also measured using a live micro-CT. In our micro-CT analyses, there was no significant difference in volume change between the E-beam treated groups and non-E-beam treated groups of the same β-TCP to PCL ratios, except for the 0% β-TCP group. However, the average volume reduction differences between the E-beam and non-E-beam groups in the same-ratio samples were 0.76% (0% TCP), 3.30% (20% TCP), 4.65% (40% TCP), and 3.67% (60% TCP). The E-beam samples generally had more volume reduction in all experimental groups. Therefore, E-beam treatment may accelerate degradation. In our live micro-CT analyses, most volume reduction arose in the first four weeks after implantation and slowed between 4 and 20 weeks in all groups. E-beam groups showed greater volume reduction at every time point, which is consistent with the results by micro-CT analysis. Histology results suggest the biocompatibility of TCP/PCL composite filaments. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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15 pages, 5168 KiB  
Article
3D Printed Wavy Scaffolds Enhance Mesenchymal Stem Cell Osteogenesis
by Shen Ji and Murat Guvendiren
Micromachines 2020, 11(1), 31; https://doi.org/10.3390/mi11010031 - 25 Dec 2019
Cited by 33 | Viewed by 6028
Abstract
There is a growing interest in developing 3D porous scaffolds with tunable architectures for bone tissue engineering. Surface topography has been shown to control stem cell behavior including differentiation. In this study, we printed 3D porous scaffolds with wavy or linear patterns to [...] Read more.
There is a growing interest in developing 3D porous scaffolds with tunable architectures for bone tissue engineering. Surface topography has been shown to control stem cell behavior including differentiation. In this study, we printed 3D porous scaffolds with wavy or linear patterns to investigate the effect of wavy scaffold architecture on human mesenchymal stem cell (hMSC) osteogenesis. Five distinct wavy scaffolds were designed using sinusoidal waveforms with varying wavelengths and amplitudes, and orthogonal scaffolds were designed using linear patterns. We found that hMSCs attached to wavy patterns, spread by taking the shape of the curvatures presented by the wavy patterns, exhibited an elongated shape and mature focal adhesion points, and differentiated into the osteogenic lineage. When compared to orthogonal scaffolds, hMSCs on wavy scaffolds showed significantly enhanced osteogenesis, indicated by higher calcium deposition, alkaline phosphatase activity, and osteocalcin staining. This study aids in the development of 3D scaffolds with novel architectures to direct stem osteogenesis for bone tissue engineering. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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13 pages, 4080 KiB  
Article
Scaffold-Free Bioprinter Utilizing Layer-By-Layer Printing of Cellular Spheroids
by Wesley LaBarge, Andrés Morales, Daniëlle Pretorius, Asher M. Kahn-Krell, Ramaswamy Kannappan and Jianyi Zhang
Micromachines 2019, 10(9), 570; https://doi.org/10.3390/mi10090570 - 29 Aug 2019
Cited by 25 | Viewed by 5354
Abstract
Free from the limitations posed by exogenous scaffolds or extracellular matrix-based materials, scaffold-free engineered tissues have immense clinical potential. Biomaterials may produce adverse responses, interfere with cell–cell interaction, or affect the extracellular matrix integrity of cells. The scaffold-free Kenzan method can generate complex [...] Read more.
Free from the limitations posed by exogenous scaffolds or extracellular matrix-based materials, scaffold-free engineered tissues have immense clinical potential. Biomaterials may produce adverse responses, interfere with cell–cell interaction, or affect the extracellular matrix integrity of cells. The scaffold-free Kenzan method can generate complex tissues using spheroids on an array of needles but could be inefficient in terms of time, as it moves and places only a single spheroid at a time. We aimed to design and construct a novel scaffold-free bioprinter that can print an entire layer of spheroids at once, effectively reducing the printing time. The bioprinter was designed using computer-aided design software and constructed from machined, 3D printed, and commercially available parts. The printing efficiency and the operating precision were examined using Zirconia and alginate beads, which mimic spheroids. In less than a minute, the printer could efficiently pick and transfer the beads to the printing surface and assemble them onto the 4 × 4 needles. The average overlap coefficient between layers was measured and found to be 0.997. As a proof of concept using human induced pluripotent stem cell-derived spheroids, we confirmed the ability of the bioprinter to place cellular spheroids onto the needles efficiently to print an entire layer of tissue. This novel layer-by-layer, scaffold-free bioprinter is efficient and precise in operation and can be easily scaled to print large tissues. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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15 pages, 6140 KiB  
Article
A Novel Biodegradable Multilayered Bioengineered Vascular Construct with a Curved Structure and Multi-Branches
by Yuanyuan Liu, Yi Zhang, Weijian Jiang, Yan Peng, Jun Luo, Shaorong Xie, Songyi Zhong, Huayan Pu, Na Liu and Tao Yue
Micromachines 2019, 10(4), 275; https://doi.org/10.3390/mi10040275 - 24 Apr 2019
Cited by 12 | Viewed by 3769
Abstract
Constructing tissue engineered vascular grafts (TEVG) is of great significance for cardiovascular research. However, most of the fabrication techniques are unable to construct TEVG with a bifurcated and curved structure. This paper presents multilayered biodegradable TEVGs with a curved structure and multi-branches. The [...] Read more.
Constructing tissue engineered vascular grafts (TEVG) is of great significance for cardiovascular research. However, most of the fabrication techniques are unable to construct TEVG with a bifurcated and curved structure. This paper presents multilayered biodegradable TEVGs with a curved structure and multi-branches. The technique combined 3D printed molds and casting hydrogel and sacrificial material to create vessel-mimicking constructs with customizable structural parameters. Compared with other fabrication methods, the proposed technique can create more native-like 3D geometries. The diameter and wall thickness of the fabricated constructs can be independently controlled, providing a feasible approach for TEVG construction. Enzymatically-crosslinked gelatin was used as the material of the constructs. The mechanical properties and thermostability of the constructs were evaluated. Fluid-structure interaction simulations were conducted to examine the displacement of the construct’s wall when blood flows through it. Human umbilical vein endothelial cells (HUVECs) were seeded on the inner channel of the constructs and cultured for 72 h. The cell morphology was assessed. The results showed that the proposed technique had good application potentials, and will hopefully provide a novel technological approach for constructing integrated vasculature for tissue engineering. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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Review

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25 pages, 4507 KiB  
Review
Advanced Polymers for Three-Dimensional (3D) Organ Bioprinting
by Xiaohong Wang
Micromachines 2019, 10(12), 814; https://doi.org/10.3390/mi10120814 - 25 Nov 2019
Cited by 58 | Viewed by 7961
Abstract
Three-dimensional (3D) organ bioprinting is an attractive scientific area with huge commercial profit, which could solve all the serious bottleneck problems for allograft transplantation, high-throughput drug screening, and pathological analysis. Integrating multiple heterogeneous adult cell types and/or stem cells along with other biomaterials [...] Read more.
Three-dimensional (3D) organ bioprinting is an attractive scientific area with huge commercial profit, which could solve all the serious bottleneck problems for allograft transplantation, high-throughput drug screening, and pathological analysis. Integrating multiple heterogeneous adult cell types and/or stem cells along with other biomaterials (e.g., polymers, bioactive agents, or biomolecules) to make 3D constructs functional is one of the core issues for 3D bioprinting of bioartificial organs. Both natural and synthetic polymers play essential and ubiquitous roles for hierarchical vascular and neural network formation in 3D printed constructs based on their specific physical, chemical, biological, and physiological properties. In this article, several advanced polymers with excellent biocompatibility, biodegradability, 3D printability, and structural stability are reviewed. The challenges and perspectives of polymers for rapid manufacturing of complex organs, such as the liver, heart, kidney, lung, breast, and brain, are outlined. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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30 pages, 21601 KiB  
Review
Chitosans for Tissue Repair and Organ Three-Dimensional (3D) Bioprinting
by Shenglong Li, Xiaohong Tian, Jun Fan, Hao Tong, Qiang Ao and Xiaohong Wang
Micromachines 2019, 10(11), 765; https://doi.org/10.3390/mi10110765 - 11 Nov 2019
Cited by 67 | Viewed by 6387
Abstract
Chitosan is a unique natural resourced polysaccharide derived from chitin with special biocompatibility, biodegradability, and antimicrobial activity. During the past three decades, chitosan has gradually become an excellent candidate for various biomedical applications with prominent characteristics. Chitosan molecules can be chemically modified, adapting [...] Read more.
Chitosan is a unique natural resourced polysaccharide derived from chitin with special biocompatibility, biodegradability, and antimicrobial activity. During the past three decades, chitosan has gradually become an excellent candidate for various biomedical applications with prominent characteristics. Chitosan molecules can be chemically modified, adapting to all kinds of cells in the body, and endowed with specific biochemical and physiological functions. In this review, the intrinsic/extrinsic properties of chitosan molecules in skin, bone, cartilage, liver tissue repair, and organ three-dimensional (3D) bioprinting have been outlined. Several successful models for large scale-up vascularized and innervated organ 3D bioprinting have been demonstrated. Challenges and perspectives in future complex organ 3D bioprinting areas have been analyzed. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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18 pages, 2183 KiB  
Review
The Applications of 3D Printing for Craniofacial Tissue Engineering
by Owen Tao, Jacqueline Kort-Mascort, Yi Lin, Hieu M. Pham, André M. Charbonneau, Osama A. ElKashty, Joseph M. Kinsella and Simon D. Tran
Micromachines 2019, 10(7), 480; https://doi.org/10.3390/mi10070480 - 17 Jul 2019
Cited by 74 | Viewed by 9210
Abstract
Three-dimensional (3D) printing is an emerging technology in the field of dentistry. It uses a layer-by-layer manufacturing technique to create scaffolds that can be used for dental tissue engineering applications. While several 3D printing methodologies exist, such as selective laser sintering or fused [...] Read more.
Three-dimensional (3D) printing is an emerging technology in the field of dentistry. It uses a layer-by-layer manufacturing technique to create scaffolds that can be used for dental tissue engineering applications. While several 3D printing methodologies exist, such as selective laser sintering or fused deposition modeling, this paper will review the applications of 3D printing for craniofacial tissue engineering; in particular for the periodontal complex, dental pulp, alveolar bone, and cartilage. For the periodontal complex, a 3D printed scaffold was attempted to treat a periodontal defect; for dental pulp, hydrogels were created that can support an odontoblastic cell line; for bone and cartilage, a polycaprolactone scaffold with microspheres induced the formation of multiphase fibrocartilaginous tissues. While the current research highlights the development and potential of 3D printing, more research is required to fully understand this technology and for its incorporation into the dental field. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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23 pages, 4952 KiB  
Review
In Vivo Tracking of Tissue Engineered Constructs
by Carmen J. Gil, Martin L. Tomov, Andrea S. Theus, Alexander Cetnar, Morteza Mahmoudi and Vahid Serpooshan
Micromachines 2019, 10(7), 474; https://doi.org/10.3390/mi10070474 - 16 Jul 2019
Cited by 29 | Viewed by 6308
Abstract
To date, the fields of biomaterials science and tissue engineering have shown great promise in creating bioartificial tissues and organs for use in a variety of regenerative medicine applications. With the emergence of new technologies such as additive biomanufacturing and 3D bioprinting, increasingly [...] Read more.
To date, the fields of biomaterials science and tissue engineering have shown great promise in creating bioartificial tissues and organs for use in a variety of regenerative medicine applications. With the emergence of new technologies such as additive biomanufacturing and 3D bioprinting, increasingly complex tissue constructs are being fabricated to fulfill the desired patient-specific requirements. Fundamental to the further advancement of this field is the design and development of imaging modalities that can enable visualization of the bioengineered constructs following implantation, at adequate spatial and temporal resolution and high penetration depths. These in vivo tracking techniques should introduce minimum toxicity, disruption, and destruction to treated tissues, while generating clinically relevant signal-to-noise ratios. This article reviews the imaging techniques that are currently being adopted in both research and clinical studies to track tissue engineering scaffolds in vivo, with special attention to 3D bioprinted tissue constructs. Full article
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine)
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