From Academia: Nanoclay Bioink, Machine Learning, Hydrogel Design Strategies for 3D Bioprinting

“From Academia” feature recent, relevant, close to commercialization academic publications in the space of healthcare 3D printing, bioprinting, and related emerging technologies. In this issue, we share three papers focusing on nanoclay bioink, machine learning algorithms, design strategies for 3D bioprinting of various applications.

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Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo

– Authored by Gianluca Cidonio, Michael Glinka, Yang-Hee Kim, Janos M Kanczler, Stuart A Lanham, Tilman Ahlfeld, Anja Lode, Jonathan I Dawson, Michael Gelinsky and Richard O C Oreffo. Biofabrication, 11 May 2020

In vivo mineralization of 3D printed scaffolds 4 weeks after implantation. Control alginate casted (i), alginate loaded BMP-2 (ii), 3D printed 3-3-3 (iii) and 3D printed 3-3-3 loaded with BMP-2 (a-iv) scaffolds showed in vivo and CT reconstruction respectively. Bone density scale indicates low-density bone as dark red and high-density bone as blue. Copyright. Biofabrication


Cellular soft hydrogels are not ideal for hard tissue engineering given their poor mechanical stability, however, in combination with cellular components offer significant promise for tissue regeneration. Indeed, nanocomposite bioinks provide an attractive platform to deliver human bone marrow stromal cells (HBMSCs) in three dimensions producing cell-laden constructs that aim to facilitate bone repair and functionality. Here we present the in vitro, ex vivo, and in vivo investigation of bioprinted HBMSCs encapsulated in a nanoclay bioink to produce viable and functional three-dimensional constructs. HBMSC-laden constructs remained viable over 21 d in vitro and immediately functional when conditioned with osteogenic media. 3D scaffolds seeded with human umbilical vein endothelial cells (HUVECs) and loaded with vascular endothelial growth factor (VEGF) implanted ex vivo into a chick chorioallantoic membrane (CAM) model showed integration and vascularisation after 7 d of incubation. In a pre-clinical in vivo application of a nanoclay bioink to regenerate skeletal tissue, we demonstrated bone morphogenetic protein-2 (BMP-2) absorbed scaffolds produced extensive mineralization after 4 weeks (p < 0.0001) compared to the drug-free and alginate controls. In addition, HBMSC-laden 3D printed scaffolds were found to significantly (p < 0.0001) support bone tissue formation in vivo compared to acellular and cast scaffolds. These studies illustrate the potential of nanoclay bioink, to produce viable and functional constructs for clinically relevant skeletal tissue regeneration.

A Perspective on Using Machine Learning in 3D Bioprinting

– Authored by Chunling Yu, Jingchao Jiang. Advanced Functional Materials. 30 January 2020

An example of using machine learning to design scaffolds for three-dimensional bioprinting. Copyright. International Journal of Bioprinting


Recently, three-dimensional (3D) printing technologies have been widely applied in industry and our daily lives. The term 3D bioprinting has been coined to describe 3D printing at the biomedical level. Machine learning is currently becoming increasingly active and has been used to improve 3D printing processes, such as process optimization, dimensional accuracy analysis, manufacturing defect detection, and material property prediction. However, few studies have been found to use machine learning in 3D bioprinting processes. In this paper, related machine learning methods used in 3D printing are briefly reviewed and a perspective on how machine learning can also benefit 3D bioprinting is discussed. We believe that machine learning can significantly affect the future development of 3D bioprinting and hope this paper can inspire some ideas on how machine learning can be used to improve 3D bioprinting.

3D printing of hydrogels: Rational design strategies and emerging biomedical applications

– Authored by Jinhua Li, Chengtie Wu, Paul K.Chu, Michael Gelinsky. Material Science and Engineering R: Reports. April 2020. 

Schematic diagram of 3D printing, 3D bioprinting, 4D printing and 4D bioprinting with ink formulations from conventional biomaterials, cells and intelligent biomaterials. Cells are encapsulated within ink materials (e.g. hydrogels, hydrogel precursors) to formulate bioinks for bioprinting. CopyrightBiotechnology Journal


3D printing alias additive manufacturing can transform 3D virtual models created by computer-aided design (CAD) into physical 3D objects in a layer-by-layer manner dispensing with conventional molding or machining. Since the incipiency, significant advancements have been achieved in understanding the process of 3D printing and the relationship of component, structure, property, and application of the created objects. Because hydrogels are one of the most feasible classes of ink materials for 3D printing and this field has been rapidly advancing, this Review focuses on hydrogel designs and the development of advanced hydrogel-based biomaterial inks and bioinks for 3D printing. It covers 3D printing techniques including laser printing (stereolithography, two-photon polymerization), extrusion printing (3D plotting, direct ink writing), inkjet printing, 3D bioprinting, 4D printing, and 4D bioprinting. It provides a comprehensive overview and discussion of the tailorability of material, mechanical, physical, chemical, and biological properties of hydrogels to enable advanced hydrogel designs for 3D printing. The range of hydrogel-forming polymers covered encompasses biopolymers, synthetic polymers, polymer blends, nanocomposites, functional polymers, and cell-laden systems. The representative biomedical applications selected demonstrate how hydrogel-based 3D printing is being exploited in tissue engineering, regenerative medicine, cancer research, in vitro disease modeling, high-throughput drug screening, surgical preparation, soft robotics, and flexible wearable electronics. Incomparable by thermoplastics, thermosets, ceramics, and metals, hydrogel-based 3D printing is playing a pivotal role in the design and creation of advanced functional (bio)systems in a customizable way. An outlook on future directions of hydrogel-based 3D printing is presented.

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