3D Printing in Biomedicine

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 44969

Special Issue Editors


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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,

3D printing, also known as additive manufacturing, has become in the forefront of research in biomedical fields. 3D printing enables fabrication of patient specific devices and tissue constructs, making attractive, alternative therapeutic solutions for medical applications. This manufacturing technology is currently used in a large variety of medical applications including dentistry, anatomical models, medical devices, tissue engineering scaffolds, tissue models, and drug formulation. 3D printing technologies include extrusion-based, vat photopolymerization, droplet-based, and powder-based printing, overall enabling to manufacture polymeric, metallic, and ceramic biomaterials as well as their composites. 3D bioprinting, refers to printing living cells and biomaterials, has enabled highly-controlled assembly of cell-laden hydrogels as well as cell suspensions and spheroids as “bioinks”. Bioprinting is an emerging biomanufacturing approach to fabricate functional tissues and organs. There is a growing demand to develop novel printable biomaterials and bioinks to achieve desired properties such as printability and end-use properties (biomechanics, degradation, bioactivity, etc.).  

In this special issue, we aim to capture current state-of-the-art research and review papers focusing on all aspects of 3D printing in medicine. Topics covered will include development of novel (bio)printing technologies and open source (bio)printers, design and utilization of printable biomaterials and bioinks, development of imaging technologies and software for (bio)printing, medical applications of 3D printing, regulatory issues and potential solutions.

Dr. Murat Guvendiren
Dr. Vahid Serpooshan
Guest Editors

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Keywords

  • Additive manufacturing
  • 3D printing technologies
  • 3D bioprinting
  • Biomanufacturing
  • Bioinks
  • Printable biomaterials
  • Tissue engineering
  • Biofabrication
  • Medical devices

Published Papers (8 papers)

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Research

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16 pages, 31871 KiB  
Article
Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation
by Jian Guan, Fu-zhen Yuan, Zi-mu Mao, Hai-lin Zhu, Lin Lin, Harry Huimin Chen and Jia-kuo Yu
Polymers 2021, 13(13), 2146; https://doi.org/10.3390/polym13132146 - 29 Jun 2021
Cited by 12 | Viewed by 3708
Abstract
The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we [...] Read more.
The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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19 pages, 17686 KiB  
Article
3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration
by Mohammadreza Shokouhimehr, Andrea S. Theus, Archana Kamalakar, Liqun Ning, Cong Cao, Martin L. Tomov, Jarred M. Kaiser, Steven Goudy, Nick J. Willett, Ho Won Jang, Christopher N. LaRock, Philip Hanna, Aron Lechtig, Mohamed Yousef, Janaina Da Silva Martins, Ara Nazarian, Mitchel B. Harris, Morteza Mahmoudi and Vahid Serpooshan
Polymers 2021, 13(7), 1099; https://doi.org/10.3390/polym13071099 - 30 Mar 2021
Cited by 24 | Viewed by 5272
Abstract
Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic [...] Read more.
Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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10 pages, 2098 KiB  
Article
Mechanical Properties and Biocompatibility of Urethane Acrylate-Based 3D-Printed Denture Base Resin
by Jy-Jiunn Tzeng, Tzu-Sen Yang, Wei-Fang Lee, Hsuan Chen and Hung-Ming Chang
Polymers 2021, 13(5), 822; https://doi.org/10.3390/polym13050822 - 8 Mar 2021
Cited by 24 | Viewed by 5603
Abstract
In this study, five urethane acrylates (UAs), namely aliphatic urethane hexa-acrylate (87A), aromatic urethane hexa-acrylate (88A), aliphatic UA (588), aliphatic urethane triacrylate diluted in 15% HDD (594), and high-functional aliphatic UA (5812), were selected to formulate five UA-based photopolymer resins for digital light [...] Read more.
In this study, five urethane acrylates (UAs), namely aliphatic urethane hexa-acrylate (87A), aromatic urethane hexa-acrylate (88A), aliphatic UA (588), aliphatic urethane triacrylate diluted in 15% HDD (594), and high-functional aliphatic UA (5812), were selected to formulate five UA-based photopolymer resins for digital light processing (DLP)-based 3D printing. Each UA (40 wt%) was added and blended homogenously with ethoxylated pentaerythritol tetraacrylate (40 wt%), isobornyl acrylate (12 wt%), diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (3 wt%), and a pink acrylic (5 wt%). Each UA-based resin specimen was designed using CAD software and fabricated using a DLP 3D printer to specific dimensions. Characteristics, mechanical properties, and cytotoxicity levels of these designed UA-based resins were investigated and compared with a commercial 3D printing denture base acrylic resin (BB base) control group at different UV exposure times. Shore hardness-measurement data and MTT assays were analyzed using a one-way analysis of variance with Bonferroni’s post hoc test, whereas viscosity, maximum strength, and modulus were analyzed using the Kruskal–Wallis test (α = 0.05). UA-based photopolymer resins with tunable mechanical properties were successfully prepared by replacing the UA materials and the UV exposure times. After 15 min of UV exposure, the 5812 and 594 groups exhibited higher viscosities, whereas the 88A and 87A groups exhibited lower viscosities compared with the BB base group. Maximum flexural strength, flexural modulus, and Shore hardness values also revealed significant differences among materials (p < 0.001). Based on MTT assay results, the UA-based photopolymer resins were nontoxic. In the present study, mechanical properties of the designed photopolymer resins could be adjusted by changing the UA or UV exposure time, suggesting that aliphatic urethane acrylate has good potential for use in the design of printable resins for DLP-type 3D printing in dental applications. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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21 pages, 2696 KiB  
Article
A 3D Bioprinted Material That Recapitulates the Perivascular Bone Marrow Structure for Sustained Hematopoietic and Cancer Models
by Caitlyn A. Moore, Zain Siddiqui, Griffin J. Carney, Yahaira Naaldijk, Khadidiatou Guiro, Alejandra I. Ferrer, Lauren S. Sherman, Murat Guvendiren, Vivek A. Kumar and Pranela Rameshwar
Polymers 2021, 13(4), 480; https://doi.org/10.3390/polym13040480 - 3 Feb 2021
Cited by 12 | Viewed by 3074
Abstract
Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) [...] Read more.
Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ, making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M): alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various diseases and also for drug screening. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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10 pages, 1932 KiB  
Article
Manufacturing and Characterization of Hybrid Bulk Voxelated Biomaterials Printed by Digital Anatomy 3D Printing
by Hyeonu Heo, Yuqi Jin, David Yang, Christopher Wier, Aaron Minard, Narendra B. Dahotre and Arup Neogi
Polymers 2021, 13(1), 123; https://doi.org/10.3390/polym13010123 - 30 Dec 2020
Cited by 15 | Viewed by 2910
Abstract
The advent of 3D digital printers has led to the evolution of realistic anatomical organ shaped structures that are being currently used as experimental models for rehearsing and preparing complex surgical procedures by clinicians. However, the actual material properties are still far from [...] Read more.
The advent of 3D digital printers has led to the evolution of realistic anatomical organ shaped structures that are being currently used as experimental models for rehearsing and preparing complex surgical procedures by clinicians. However, the actual material properties are still far from being ideal, which necessitates the need to develop new materials and processing techniques for the next generation of 3D printers optimized for clinical applications. Recently, the voxelated soft matter technique has been introduced to provide a much broader range of materials and a profile much more like the actual organ that can be designed and fabricated voxel by voxel with high precision. For the practical applications of 3D voxelated materials, it is crucial to develop the novel high precision material manufacturing and characterization technique to control the mechanical properties that can be difficult using the conventional methods due to the complexity and the size of the combination of materials. Here we propose the non-destructive ultrasound effective density and bulk modulus imaging to evaluate 3D voxelated materials printed by J750 Digital Anatomy 3D Printer of Stratasys. Our method provides the design map of voxelated materials and substantially broadens the applications of 3D digital printing in the clinical research area. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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14 pages, 2661 KiB  
Article
Detailed Thermal Characterization of Acrylonitrile Butadiene Styrene and Polylactic Acid Based Carbon Composites Used in Additive Manufacturing
by Zoltan Ujfalusi, Attila Pentek, Roland Told, Adam Schiffer, Miklos Nyitrai and Peter Maroti
Polymers 2020, 12(12), 2960; https://doi.org/10.3390/polym12122960 - 11 Dec 2020
Cited by 12 | Viewed by 3162
Abstract
Currently, 3D printing is an affordable technology for industry, healthcare, and individuals. Understanding the mechanical properties and thermoplastic behaviour of the composites is critical for the users. Our results give guidance for certain target groups including professionals in the field of additive manufacturing [...] Read more.
Currently, 3D printing is an affordable technology for industry, healthcare, and individuals. Understanding the mechanical properties and thermoplastic behaviour of the composites is critical for the users. Our results give guidance for certain target groups including professionals in the field of additive manufacturing for biomedical components with in-depth characterisation of the examined commercially available ABS and PLA carbon-based composites. The study aimed to characterize these materials in terms of thermal behaviour and structure. The result of the heating-cooling loops is the thermal hysteresis effect of Ohmic resistance with its accommodation property in the temperature range of 20–84 °C for ESD-ABS and 20–72 °C for ESD-PLA. DSC-TGA measurements showed that the carbon content of the examined ESD samples is ~10–20% (m/m) and there is no significant difference in the thermodynamic behaviour of the basic ABS/PLA samples and their ESD compounds within the temperature range typically used for 3D printing. The results support the detailed design process of 3D-printed electrical components and prove that ABS and PLA carbon composites are suitable for prototyping and the production of biomedical sensors. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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Review

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25 pages, 1357 KiB  
Review
Dental 3D-Printing: Transferring Art from the Laboratories to the Clinics
by Sangeeth Pillai, Akshaya Upadhyay, Parisa Khayambashi, Imran Farooq, Hisham Sabri, Maryam Tarar, Kyungjun T. Lee, Ingrid Harb, Stephanie Zhou, Yifei Wang and Simon D. Tran
Polymers 2021, 13(1), 157; https://doi.org/10.3390/polym13010157 - 4 Jan 2021
Cited by 88 | Viewed by 12462
Abstract
The rise of three-dimensional (3D) printing technology has changed the face of dentistry over the past decade. 3D printing is a versatile technique that allows the fabrication of fully automated, tailor-made treatment plans, thereby delivering personalized dental devices and aids to the patients. [...] Read more.
The rise of three-dimensional (3D) printing technology has changed the face of dentistry over the past decade. 3D printing is a versatile technique that allows the fabrication of fully automated, tailor-made treatment plans, thereby delivering personalized dental devices and aids to the patients. It is highly efficient, reproducible, and provides fast and accurate results in an affordable manner. With persistent efforts among dentists for refining their practice, dental clinics are now acclimatizing from conventional treatment methods to a fully digital workflow to treat their patients. Apart from its clinical success, 3D printing techniques are now employed in developing haptic simulators, precise models for dental education, including patient awareness. In this narrative review, we discuss the evolution and current trends in 3D printing applications among various areas of dentistry. We aim to focus on the process of the digital workflow used in the clinical diagnosis of different dental conditions and how they are transferred from laboratories to clinics. A brief outlook on the most recent manufacturing methods of 3D printed objects and their current and future implications are also discussed. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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19 pages, 2379 KiB  
Review
Bioprintability: Physiomechanical and Biological Requirements of Materials for 3D Bioprinting Processes
by Andrea S. Theus, Liqun Ning, Boeun Hwang, Carmen Gil, Shuai Chen, Allison Wombwell, Riya Mehta and Vahid Serpooshan
Polymers 2020, 12(10), 2262; https://doi.org/10.3390/polym12102262 - 1 Oct 2020
Cited by 67 | Viewed by 7486
Abstract
Three-dimensional (3D) bioprinting is an additive manufacturing process that utilizes various biomaterials that either contain or interact with living cells and biological systems with the goal of fabricating functional tissue or organ mimics, which will be referred to as bioinks. These bioinks are [...] Read more.
Three-dimensional (3D) bioprinting is an additive manufacturing process that utilizes various biomaterials that either contain or interact with living cells and biological systems with the goal of fabricating functional tissue or organ mimics, which will be referred to as bioinks. These bioinks are typically hydrogel-based hybrid systems with many specific features and requirements. The characterizing and fine tuning of bioink properties before, during, and after printing are therefore essential in developing reproducible and stable bioprinted constructs. To date, myriad computational methods, mechanical testing, and rheological evaluations have been used to predict, measure, and optimize bioinks properties and their printability, but none are properly standardized. There is a lack of robust universal guidelines in the field for the evaluation and quantification of bioprintability. In this review, we introduced the concept of bioprintability and discussed the significant roles of various physiomechanical and biological processes in bioprinting fidelity. Furthermore, different quantitative and qualitative methodologies used to assess bioprintability will be reviewed, with a focus on the processes related to pre, during, and post printing. Establishing fully characterized, functional bioink solutions would be a big step towards the effective clinical applications of bioprinted products. Full article
(This article belongs to the Special Issue 3D Printing in Biomedicine)
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