Table of Contents

Special Section: Bioprinting of 3D Functional Tissue Constructs

Regular Section

Review article

by Natanael Parningotan Agung, Muhammad Hanif Nadhif, Gampo Alam Irdam, Chaidir Arif Mochtar

Urology is one of the fields that are always at the frontline of bringing scientific advancements into clinical practice, including 3D printing (3DP). This study aims to discuss and presents the current role of 3D-printed phantoms and devices for organ-specified applications in urology. The discussion started with a literature search regarding the two mentioned
topics within PubMed, Embase, Scopus, and EBSCOhost databases. 3D-printed urological organ phantoms are reported for providing residents new insight regarding anatomical characteristics of organs, either normal or diseased, in a tangible manner. Furthermore, 3D-printed organ phantoms also helped urologists to prepare a pre-surgical planning strategy with detailed anatomical models of the diseased organs. In some centers, 3DP technology also contributed to developing specified devices
for disease management. To date, urologists have been benefitted by 3D-printed phantoms and devices in the education and disease management of organs of in the genitourinary system, including kidney, bladder, prostate, ureter, urethra, penis, and adrenal. It is safe to say that 3DP technology can bring remarkable changes to daily urological practices.

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Review article

by Yintao Zhang, Shokouh Attarilar, Liqiang Wang, Weijie Lu, Junlin Yang, Yuanfei Fu

NiTi alloy has a wide range of applications as a biomaterial due to its high ductility, low corrosion rate, and favorable biocompatibility. Although Young’s modulus of NiTi is relatively low, it still needs to be reduced; one of the promising ways is by introducing porous structure. Traditional manufacturing processes, such as casting, can hardly produce complex porous structures. Additive manufacturing (AM) is one of the most advanced manufacturing technologies that can solve impurity issues, and selective laser melting (SLM) is one of the well-known methods. This paper reviews the developments of AMNiTi with a particular focus on SLM-NiTi utilization in biomedical applications. Correspondingly, this paper aims to describe the three key factors, including powder preparation, processing parameters, and gas atmosphere during the overall process of porous NiTi. The porous structure design is of vital importance, so the unit cell and pore parameters are discussed. The mechanical properties of SLM-NiTi, such as hardness, compressive strength, tensile strength, fatigue behavior, and damping properties and their relationship with design parameters are summarized. In the end, it points out the current challenges. Considering the increasing application of NiTi implants, this review paper may open new frontiers for advanced and modern designs.

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Original research article

by Evangelos Daskalakis, Fengyuan Liu, Boyang Huang, Anil A. Acar, Glen Cooper, Andrew Weightman, Gordon Blunn, Bahattin Koç, Paulo Bartolo

There is a significant unmet clinical need to prevent amputations due to large bone loss injuries. We are addressing this problem by developing a novel, cost-effective osseointegrated prosthetic solution based on the use of modular pieces, bone bricks, made with biocompatible and biodegradable materials that fit together in a Lego-like way to form the prosthesis. This paper investigates the anatomical designed bone bricks with different architectures, pore size gradients, and material compositions. Polymer and polymer-composite 3D printed bone bricks are extensively morphological, mechanical, and biological characterized. Composite bone bricks were produced by mixing polycaprolactone (PCL) with different levels of hydroxyapatite (HA) and β-tri-calcium phosphate (TCP). Results allowed to establish a correlation between bone bricks
architecture and material composition and bone bricks performance. Reinforced bone bricks showed improved mechanical and biological results. Best mechanical properties were obtained with PCL/TCP bone bricks with 38 double zig-zag filaments and 14 spiral-like pattern filaments, while the best biological results were obtained with PCL/HA bone bricks based on 25 double zig-zag filaments and 14 spiral-like pattern filaments.

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Original research article

by Wei Long Ng, Teck Choon Ayi, Yi-Chun Liu, Swee Leong Sing, Wai Yee Yeong, Boon-Huan Tan

The global prevalence of respiratory diseases caused by infectious pathogens has resulted in an increased demand for realistic in-vitro alveolar lung models to serve as suitable disease models. This demand has resulted in the fabrication of numerous two-dimensional (2D) and three-dimensional (3D) in-vitro alveolar lung models. The ability to fabricate these 3D in-vitro alveolar lung models in an automated manner with high repeatability and reliability is important for potential scalable
production. In this study, we reported the fabrication of human triple-layered alveolar lung models comprising of human lung epithelial cells, human endothelial cells, and human lung fibroblasts using the drop-on-demand (DOD) 3D bioprinting technique. The polyvinylpyrrolidone-based bio-inks and the use of a 300 μm nozzle diameter improved the repeatability of the bioprinting process by achieving consistent cell output over time using different human alveolar lung cells. The 3D bioprinted
human triple-layered alveolar lung models were able to maintain cell viability with relative similar proliferation profile over time as compared to non-printed cells. This DOD 3D bioprinting platform offers an attractive tool for highly repeatable and scalable fabrication of 3D in-vitro human alveolar lung models.

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Original research article

by Sara Cristina Pedroza-González, Marisela Rodriguez-Salvador, Baruc Emet Pérez Benítez, Mario Moisés Alvarez, Grissel Trujillo-de Santiago

This scientometric analysis of 393 original papers published from January 2000 to June 2019 describes the development and use of bioinks for 3D bioprinting. The main trends for bioink applications and the primary considerations guiding the selection and design of current bioink components (i.e., cell types, hydrogels, and additives) were reviewed. The cost, availability, practicality, and basic biological considerations (e.g., cytocompatibility and cell attachment) are the most popular parameters guiding bioink use and development. Today, extrusion bioprinting is the most widely used bioprinting technique. The most reported use of bioinks is the generic characterization of bioink formulations or bioprinting technologies (32%), followed by cartilage bioprinting applications (16%). Similarly, the cell-type choice is mostly generic, as cells are typically used as models to assess bioink formulations or new bioprinting methodologies rather than to fabricate specific tissues. The cell-binding motif arginine-glycine-aspartate is the most common bioink additive. Many articles reported the development of advanced functional bioinks for specific biomedical applications; however, most bioinks remain the basic compositions that meet the simple criteria: Manufacturability and essential biological performance. Alginate and gelatin methacryloyl are the most popular hydrogels that meet these criteria. Our analysis suggests that present-day bioinks still represent a stage of emergence of bioprinting technology.

Original research article

by Guowen Qian, Lemin Zhang, Guoyong Wang, Zhengyu Zhao, Shuping Peng, Cijun Shuai

Poly-L-lactic acid (PLLA) lacks osteogenic activity, which limits its application in bone repair. Zinc (Zn) is widely applied to strengthen the biological properties of polymers due to its excellent osteogenic activity. In the present study, Zn-doped mesoporous silica (Zn-MS) particles were synthesized by one-pot hydrothermal method. Then, the particles were induced into PLLA scaffolds prepared by selective laser sintering technique, aiming to improve their osteogenic activity. Our results showed that the synthesized particles possessed rosette-like morphology and uniform mesoporous structure, and the composite scaffold displayed the sustained release of Zn ion in a low concentration range, which was attributed to the shield effect of the PLLA matrix and the strong bonding interaction of Si-O-Zn. The scaffold could evidently promote osteogenesis
differentiation of mouse bone marrow mesenchymal stem cells by upregulating their osteogenesis-related gene expression. Besides, Zn-MS particles could significantly increase the compressive strength of the PLLA scaffold because of their rosettelike morphology and mesoporous structure, which can form micromechanical interlocking with the PLLA matrix. The Zn-MS particles possess great potential to improve various polymer scaffold properties due to their advantageous morphology and
physicochemical properties.

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Original research article

by N. V. Arguchinskaya, E. E. Beketov, A. A Kisel, E. V. Isaeva, E. O. Osidak, S. P. Domogatsky, N. V. Mikhailovsky, F. E. Sevryukov, N. K. Silantyeva, T. A. Agababyan, S. A. Ivanov, P. V. Shegay, A. D. Kaprin

During biofabrication, a tissue scaffold may require temporary support. The aim of this study was to develop an approach of human thyroid cartilage scaffold temporal support formation. The scaffold 3D-model was based on DICOM images. XY plane projections were used to form scaffold supporting part. To verify the technique, collagen hydrogel was chosen as the main scaffold component. Gelatin was applied for the supporting part. To test the applicability of the approach, a model of thyroid cartilage scaffold with the support was printed. The scaffold corresponded to a given model, although some discrepancy in geometry was observed during verification by computed tomography.

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Original research article

by Cheng Pau Lee, Jon Yi Hoo, Michinao Hashimoto

We developed a method to perform direct ink writing (DIW) three-dimensional (3D) printing of coconut-basedvproducts with high oil content by varying compositions of the coconut oil and the coconut cream. The addition of oils is particularly crucial in providing energy, developing neurological functions, and improving the palatability of food. Despite the potential merits of high oil-content foods, there have been limited studies on 3D printing of high oil-content foods. In particular, the effect of oil content on the printability of food inks has not been studied to date. 3D printing of food inks with high oil contents is challenging due to oil separation that leads to unpredictable changes in rheological properties. In this work, we surveyed the behavior of the mixture of the coconut oil and the coconut cream and identified the appropriate conditions for the food inks that show the printability in DIW 3D printing. We initially formulated coconut cream inks added with coconut
oil that did not exhibit oil separation, and characterized the rheological properties of such inks. We successfully 3D-printed coconut cream with additional coconut oil and successfully fabricated 3D structures with inks containing 25% water with an additional 10% (w/w) of coconut oil. Texture profile analysis (TPA) suggested that the hardness index and the chewiness index of mesh-shaped 3D-printed coconut cream decreased due to an increase in the water content of the ink. Overall, this study
offered an understanding of the stability of the food inks and demonstrated the fabrication of 3D colloidal food with controlled
oil content, which can be applied to formulating foods with tunable oil content to cater to individual nutritional needs without compromising the stability of the inks.