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3D Printing for Biomedical Engineering

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Manufacturing Processes and Systems".

Deadline for manuscript submissions: closed (15 January 2017) | Viewed by 145595

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Special Issue Editors

Prof. Dr. Chee Kai Chua

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Guest Editor

Singapore Centre for 3D Printing, School of Mechanical & Aerospace Engineering, Nanyang Technological University, N3.1-B2c-03b, 50 Nanyang Avenue, Singapore 639798, Singapore
Interests: geometric modelling; rapid prototyping; additive manufacturing; 3D printing; reverse engineering; biomedical engineering design; tissue engineering; biomaterials; bioprinting
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Wai Yee Yeong

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Guest Editor

Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore
Interests: additive manufacturing; 3D printing; 3D bioprinting
Special Issues, Collections and Topics in MDPI journals

Dr. Jia An

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Guest Editor

Singapore Centre for 3D Printing, School of Mechanical & Aerospace Engineering, Nanyang Technological University, N3.1-B2c-03b, 50 Nanyang Avenue, Singapore 639798, Singapore
Interests: 3D printing; bioprinting; biomaterials; polymer processing; polymer microfibers; polymer membranes; tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In biomedical engineering, 3D printing (also known as additive manufacturing or rapid prototyping) offers a number of distinct advantages over conventional fabrication, for instance freeform fabrication, high customization, and cost effectiveness with multifunctional potentials.

This Special Issue focuses on recent developments of various 3D printing technologies and their new applications in biomedical engineering. A wide range of topics are covered, including (but not limited to) new biomaterials for 3D printing, biomechanical analysis of 3D printed parts, 3D printed devices for medical/cancer imaging and diagnostics, 3D printed auxiliary devices for genetic engineering and cell biology, 3D printing of novel medical devices (e.g., prostheses/implants/scaffolds), sterilization and quality inspection of 3D printed medical devices, bioprinting of living tissues/organs, 3D printed bionic devices, 3D printing of pharmaceuticals and drug delivery devices, 3D printing for clinical and rehabilitation engineering, food printing, 4D printing, regulations and legal aspects of 3D printed biomedical products, 3D printing in medical education and training; and case studies in which 3D printing provides a unique solution to biomedical challenges.

In summary, we encourage all manuscript submissions that involve 3D printing and a subject of matter in biomedical engineering as within the scope of this Special Issue.

Prof. Dr. Chee Kai Chua
Asst. Prof. Wai Yee Yeong
Dr. Jia An
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Materials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

biomanufacturing
biofabrication
biomaterials in 3D printing
biomechanical analysis of 3D printed parts
bioimaging for printed 3D construct
3D printed diagnostics and lab-on-chips
printed medical implants
complex 3D printed scaffolds for tissue engineering
tissue engineering and drug delivery
bioprinting and food printing
4D printing and 4D bioprinting
visualization in 3D printing for biomedical applications
sterilization and quality inspection of 3D printed medical devices
case study

Published Papers (14 papers)

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Editorial

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157 KiB

Open AccessEditorial

Special Issue: 3D Printing for Biomedical Engineering

by Chee Kai Chua, Wai Yee Yeong and Jia An

Materials 2017, 10(3), 243; https://doi.org/10.3390/ma10030243 - 28 Feb 2017

Cited by 19 | Viewed by 6692

Abstract

Three-dimensional (3D) printing has a long history of applications in biomedical engineering. The development and expansion of traditional biomedical applications are being advanced and enriched by new printing technologies. New biomedical applications such as bioprinting are highly attractive and trendy. This Special Issue [...] Read more.

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

Research

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2751 KiB

Open AccessArticle

Polyvinylpyrrolidone-Based Bio-Ink Improves Cell Viability and Homogeneity during Drop-On-Demand Printing

by Wei Long Ng, Wai Yee Yeong and May Win Naing

Materials 2017, 10(2), 190; https://doi.org/10.3390/ma10020190 - 16 Feb 2017

Cited by 80 | Viewed by 7821

Abstract

Drop-on-demand (DOD) bioprinting has attracted huge attention for numerous biological applications due to its precise control over material volume and deposition pattern in a contactless printing approach. 3D bioprinting is still an emerging field and more work is required to improve the viability and homogeneity of printed cells during the printing process. Here, a general purpose bio-ink was developed using polyvinylpyrrolidone (PVP) macromolecules. Different PVP-based bio-inks (0%–3% w/v) were prepared and evaluated for their printability; the short-term and long-term viability of the printed cells were first investigated. The Z value of a bio-ink determines its printability; it is the inverse of the Ohnesorge number (Oh), which is the ratio between the Reynolds number and a square root of the Weber number, and is independent of the bio-ink velocity. The viability of printed cells is dependent on the Z values of the bio-inks; the results indicated that the cells can be printed without any significant impairment using a bio-ink with a threshold Z value of ≤9.30 (2% and 2.5% w/v). Next, the cell output was evaluated over a period of 30 min. The results indicated that PVP molecules mitigate the cell adhesion and sedimentation during the printing process; the 2.5% w/v PVP bio-ink demonstrated the most consistent cell output over a period of 30 min. Hence, PVP macromolecules can play a critical role in improving the cell viability and homogeneity during the bioprinting process. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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Open AccessArticle

3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications

by Ming-You Shie, Wen-Ching Chang, Li-Ju Wei, Yu-Hsin Huang, Chien-Han Chen, Cheng-Ting Shih, Yi-Wen Chen and Yu-Fang Shen

Materials 2017, 10(2), 136; https://doi.org/10.3390/ma10020136 - 8 Feb 2017

Cited by 118 | Viewed by 9497

Abstract

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton’s jelly mesenchymal stem cells (hWJMSCs) and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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6397 KiB

Open AccessArticle

Laser Sintered Magnesium-Calcium Silicate/Poly-ε-Caprolactone Scaffold for Bone Tissue Engineering

by Kuo-Yang Tsai, Hung-Yang Lin, Yi-Wen Chen, Cheng-Yao Lin, Tuan-Ti Hsu and Chia-Tze Kao

Materials 2017, 10(1), 65; https://doi.org/10.3390/ma10010065 - 13 Jan 2017

Cited by 61 | Viewed by 7305

Abstract

In this study, we manufacture and analyze bioactive magnesium–calcium silicate/poly-ε-caprolactone (Mg–CS/PCL) 3D scaffolds for bone tissue engineering. Mg–CS powder was incorporated into PCL, and we fabricated the 3D scaffolds using laser sintering technology. These scaffolds had high porosity and interconnected-design macropores and structures. As compared to pure PCL scaffolds without an Mg–CS powder, the hydrophilic properties and degradation rate are also improved. For scaffolds with more than 20% Mg–CS content, the specimens become completely covered by a dense bone-like apatite layer after soaking in simulated body fluid for 1 day. In vitro analyses were directed using human mesenchymal stem cells (hMSCs) on all scaffolds that were shown to be biocompatible and supported cell adhesion and proliferation. Increased focal adhesion kinase and promoted cell adhesion behavior were observed after an increase in Mg–CS content. In addition, the results indicate that the Mg–CS quantity in the composite is higher than 10%, and the quantity of cells and osteogenesis-related protein of hMSCs is stimulated by the Si ions released from the Mg–CS/PCL scaffolds when compared to PCL scaffolds. Our results proved that 3D Mg–CS/PCL scaffolds with such a specific ionic release and good degradability possessed the ability to promote osteogenetic differentiation of hMSCs, indicating that they might be promising biomaterials with potential for next-generation bone tissue engineering scaffolds. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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Open AccessArticle

Customized a Ti6Al4V Bone Plate for Complex Pelvic Fracture by Selective Laser Melting

by Di Wang, Yimeng Wang, Shibiao Wu, Hui Lin, Yongqiang Yang, Shicai Fan, Cheng Gu, Jianhua Wang and Changhui Song

Materials 2017, 10(1), 35; https://doi.org/10.3390/ma10010035 - 4 Jan 2017

Cited by 60 | Viewed by 10724

Abstract

In pelvic fracture operations, bone plate shaping is challenging and the operation time is long. To address this issue, a customized bone plate was designed and produced using selective laser melting (SLM) technology. The key steps of this study included designing the customized bone plate, metal 3D printing, vacuum heat treatment, surface post-processing, operation rehearsal, and clinical application and evaluation. The joint surface of the bone plate was placed upwards with respect to the build platform to keep it away from the support and to improve the quality of the joint surface. Heat conduction was enhanced by adding a cone-type support beneath the bone plate to prevent low-quality fabrication due to poor heat conductivity of the Ti-6Al-4V powder. The residual stress was eliminated by exposing the SLM-fabricated titanium-alloy bone plate to a vacuum heat treatment. Results indicated that the bone plate has a hardness of HV1 360–HV1 390, an ultimate tensile strength of 1000–1100 MPa, yield strength of 900–950 MPa, and an elongation of 8%–10%. Pre-operative experiments and operation rehearsal were performed using the customized bone plate and the ABC-made pelvic model. Finally, the customized bone plate was clinically applied. The intraoperative C-arm and postoperative X-ray imaging results indicated that the customized bone plate matched well to the damaged pelvis. The customized bone plate fixed the broken bone and guides pelvis restoration while reducing operation time to about two hours. The customized bone plate eliminated the need for preoperative titanium plate pre-bending, thereby greatly reducing surgical wounds and operation time. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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8714 KiB

Open AccessArticle

Enhancing the Hydrophilicity and Cell Attachment of 3D Printed PCL/Graphene Scaffolds for Bone Tissue Engineering

by Weiguang Wang, Guilherme Caetano, William Stephen Ambler, Jonny James Blaker, Marco Andrey Frade, Parthasarathi Mandal, Carl Diver and Paulo Bártolo

Materials 2016, 9(12), 992; https://doi.org/10.3390/ma9120992 - 7 Dec 2016

Cited by 251 | Viewed by 12021

Abstract

Scaffolds are physical substrates for cell attachment, proliferation, and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements, i.e., certain standards in terms of mechanical properties, surface characteristics, porosity, degradability, and biocompatibility. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes, as well as surface treatment. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This paper investigates the use of an extrusion-based additive manufacturing system to produce poly(ε-caprolactone) (PCL)/pristine graphene scaffolds for bone tissue applications and the influence of chemical surface modification on their biological behaviour. Scaffolds with the same architecture but different concentrations of pristine graphene were evaluated from surface property and biological points of view. Results show that the addition of pristine graphene had a positive impact on cell viability and proliferation, and that surface modification leads to improved cell response. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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Open AccessArticle

Additive Manufacturing of Patient-Customizable Scaffolds for Tubular Tissues Using the Melt-Drawing Method

by Yu Jun Tan, Xipeng Tan, Wai Yee Yeong and Shu Beng Tor

Materials 2016, 9(11), 893; https://doi.org/10.3390/ma9110893 - 3 Nov 2016

Cited by 15 | Viewed by 6496

Abstract

Polymeric fibrous scaffolds for guiding cell growth are designed to be potentially used for the tissue engineering (TE) of tubular organs including esophagi, blood vessels, tracheas, etc. Tubular scaffolds were fabricated via melt-drawing of highly elastic poly(l-lactide-co-ε-caprolactone) (PLC) fibers layer-by-layer on a cylindrical mandrel. The diameter and length of the scaffolds are customizable via 3D printing of the mandrel. Thickness of the scaffolds was varied by changing the number of layers of the melt-drawing process. The morphology and tensile properties of the PLC fibers were investigated. The fibers were highly aligned with a uniform diameter. Their diameters and tensile properties were tunable by varying the melt-drawing speeds. These tailorable topographies and tensile properties show that the additive-based scaffold fabrication technique is customizable at the micro- and macro-scale for different tubular tissues. The merits of these scaffolds in TE were further shown by the finding that myoblast and fibroblast cells seeded onto the scaffolds in vitro showed appropriate cell proliferation and distribution. Human mesenchymal stem cells (hMSCs) differentiated to smooth muscle lineage on the microfibrous scaffolds in the absence of soluble induction factors, showing cellular shape modulation and scaffold elasticity may encourage the myogenic differentiation of stem cells. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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5701 KiB

Open AccessArticle

Synthesis and Characterization of Types A and B Gelatin Methacryloyl for Bioink Applications

by Bae Hoon Lee, Nathaniel Lum, Li Yuan Seow, Pei Qi Lim and Lay Poh Tan

Materials 2016, 9(10), 797; https://doi.org/10.3390/ma9100797 - 24 Sep 2016

Cited by 158 | Viewed by 13889

Abstract

Gelatin methacryloyl (GelMA) has been increasingly considered as an important bioink material due to its tailorable mechanical properties, good biocompatibility, and ability to be photopolymerized in situ as well as printability. GelMA can be classified into two types: type A GelMA (a product from acid treatment) and type B GelMA (a product from alkali treatment). In current literature, there is little research on the comparison of type A GelMA and type B GelMA in terms of synthesis, rheological properties, and printability for bioink applications. Here, we report the synthesis, rheological properties, and printability of types A and B GelMA. Types A and B GelMA samples with different degrees of substitution (DS) were prepared in a controllable manner by a time-lapse loading method of methacrylic anhydride (MAA) and different feed ratios of MAA to gelatin. Type B GelMA tended to have a slightly higher DS compared to type A GelMA, especially in a lower feed ratio of MAA to gelatin. All the type A and type B GelMA solutions with different DS exhibited shear thinning behaviours at 37 °C. However, only GelMA with a high DS had an easy-to-extrude feature at room temperature. The cell-laden printed constructs of types A and B GelMA at 20% w/v showed around 75% cell viability. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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4859 KiB

Open AccessFeature PaperArticle

A Mathematical Model on the Resolution of Extrusion Bioprinting for the Development of New Bioinks

by Ratima Suntornnond, Edgar Yong Sheng Tan, Jia An and Chee Kai Chua

Materials 2016, 9(9), 756; https://doi.org/10.3390/ma9090756 - 6 Sep 2016

Cited by 110 | Viewed by 10306

Abstract

Pneumatic extrusion-based bioprinting is a recent and interesting technology that is very useful for biomedical applications. However, many process parameters in the bioprinter need to be fully understood in order to print at an adequate resolution. In this paper, a simple yet accurate mathematical model to predict the printed width of a continuous hydrogel line is proposed, in which the resolution is expressed as a function of nozzle size, pressure, and printing speed. A thermo-responsive hydrogel, pluronic F127, is used to validate the model predictions. This model could provide a platform for future correlation studies on pneumatic extrusion-based bioprinting as well as for developing new bioink formulations. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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Open AccessArticle

Design and Fabrication of a Precision Template for Spine Surgery Using Selective Laser Melting (SLM)

by Di Wang, Yimeng Wang, Jianhua Wang, Changhui Song, Yongqiang Yang, Zimian Zhang, Hui Lin, Yongqiang Zhen and Suixiang Liao

Materials 2016, 9(7), 608; https://doi.org/10.3390/ma9070608 - 22 Jul 2016

Cited by 40 | Viewed by 11004

Abstract

In order to meet the clinical requirements of spine surgery, this paper proposes the fabrication of the customized template for spine surgery through computer-aided design. A 3D metal printing-selective laser melting (SLM) technique was employed to directly fabricate the 316L stainless steel template, and the metal template with tiny locating holes was used as an auxiliary tool to insert spinal screws inside the patient’s body. To guarantee accurate fabrication of the template for cervical vertebra operation, the contact face was placed upwards to improve the joint quality between the template and the cervical vertebra. The joint surface of the printed template had a roughness of Ra = 13 ± 2 μm. After abrasive blasting, the surface roughness was Ra = 7 ± 0.5 μm. The surgical metal template was bound with the 3D-printed Acrylonitrile Butadiene Styrene (ABS) plastic model. The micro-hardness values determined at the cross-sections of SLM-processed samples varied from HV0.3 250 to HV0.3 280, and the measured tensile strength was in the range of 450 MPa to 560 MPa, which showed that the template had requisite strength. Finally, the metal template was clinically used in the patient’s surgical operation, and the screws were inserted precisely as the result of using the auxiliary template. The geometrical parameters of the template hole (e.g., diameter and wall thickness) were optimized, and measures were taken to optimize the key geometrical units (e.g., hole units) in metal 3D printing. Compared to the traditional technology of screw insertion, the use of the surgical metal template enabled the screws to be inserted more easily and accurately during spinal surgery. However, the design of the high-quality template should fully take into account the clinical demands of surgeons, as well as the advice of the designing engineers and operating technicians. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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Review

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1696 KiB

Open AccessReview

An Overview of Scaffold Design and Fabrication Technology for Engineered Knee Meniscus

by Jie Sun, Sanjairaj Vijayavenkataraman and Hang Liu

Materials 2017, 10(1), 29; https://doi.org/10.3390/ma10010029 - 3 Jan 2017

Cited by 66 | Viewed by 13458

Abstract

Current surgical treatments for meniscal tears suffer from subsequent degeneration of knee joints, limited donor organs and inconsistent post-treatment results. Three clinical scaffolds (Menaflex CMI, Actifit^® scaffold and NUsurface^® Meniscus Implant) are available on the market, but additional data are needed to properly evaluate their safety and effectiveness. Thus, many scaffold-based research activities have been done to develop new materials, structures and fabrication technologies to mimic native meniscus for cell attachment and subsequent tissue development, and restore functionalities of injured meniscus for long-term effects. This study begins with a synopsis of relevant structural features of meniscus and goes on to describe the critical considerations. Promising advances made in the field of meniscal scaffolding technology, in terms of biocompatible materials, fabrication methods, structure design and their impact on mechanical and biological properties are discussed in detail. Among all the scaffolding technologies, additive manufacturing (AM) is very promising because of its ability to precisely control fiber diameter, orientation, and pore network micro-architecture to mimic the native meniscus microenvironment. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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7626 KiB

Open AccessReview

Additive Manufacturing of Biomedical Constructs with Biomimetic Structural Organizations

by Xiao Li, Jiankang He, Weijie Zhang, Nan Jiang and Dichen Li

Materials 2016, 9(11), 909; https://doi.org/10.3390/ma9110909 - 9 Nov 2016

Cited by 26 | Viewed by 8403

Abstract

Additive manufacturing (AM), sometimes called three-dimensional (3D) printing, has attracted a lot of research interest and is presenting unprecedented opportunities in biomedical fields, because this technology enables the fabrication of biomedical constructs with great freedom and in high precision. An important strategy in AM of biomedical constructs is to mimic the structural organizations of natural biological organisms. This can be done by directly depositing cells and biomaterials, depositing biomaterial structures before seeding cells, or fabricating molds before casting biomaterials and cells. This review organizes the research advances of AM-based biomimetic biomedical constructs into three major directions: 3D constructs that mimic tubular and branched networks of vasculatures; 3D constructs that contains gradient interfaces between different tissues; and 3D constructs that have different cells positioned to create multicellular systems. Other recent advances are also highlighted, regarding the applications of AM for organs-on-chips, AM-based micro/nanostructures, and functional nanomaterials. Under this theme, multiple aspects of AM including imaging/characterization, material selection, design, and printing techniques are discussed. The outlook at the end of this review points out several possible research directions for the future. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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5557 KiB

Open AccessReview

3D Bioprinting Technologies for Hard Tissue and Organ Engineering

by Xiaohong Wang, Qiang Ao, Xiaohong Tian, Jun Fan, Yujun Wei, Weijian Hou, Hao Tong and Shuling Bai

Materials 2016, 9(10), 802; https://doi.org/10.3390/ma9100802 - 27 Sep 2016

Cited by 122 | Viewed by 21736 | Correction

Abstract

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering. Full article

(This article belongs to the Special Issue 3D Printing for Biomedical Engineering)

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