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3D Printing: The Versatile Innovation at the Healthcare Forefront.

Healthcare Cost Effectiveness in Singapore.

For the month of October 2021, APBN explores astrobiology and the planetary sciences. In Features, we look into the age-old question: are we alone in the Universe? If not, how might life emerge elsewhere in the Cosmos and taking what we know now, where do we go from here? Then we have a special contribution by Professor Chandra Wickramasinghe, astronomer and pioneer of astrobiology, who discusses the Panspermia theory and the role of culture in delaying the acceptance of the theory. In Columns, we review the latest human gene therapy trials using adeno-associated viruses as vectors to treat neurodegenerative disorders. Finally, in Spotlights, we share highlights from a conference by SGInnovate and CATALYST potential of bioprinting in personalised medicine and an interview with Dr. Senthil Sockalingam, Head of IQVIA Biotech, JAPAC & Chief Medical Officer, APAC, on its expansion in the Asia-Pacific and how the company's new innovative approach will utilise data and analytics to accelerate clinical development.

Biofabrication technologies involve the incorporation of living cells into various bioproducts by employing different cell manipulation techniques. Among them, bioprinting, delivering cell suspension through a fine needle under pressurized air, has been widely used because of its capability of precise process control. In the cell-printing process of bioprinting, cells are exposed to fluid stresses due to the velocity gradient in the fine needle. If the stresses exceed a certain level, the cell membrane may be overstretched, leading to membrane failure and thus causing mechanical cell damage. Modeling the mechanical cell damage in the bioprinting process is a challenging task due to the complex fluid flow and cell deformation involved. This paper introduces a novel method based on computational fluid dynamics (CFD) to represent the mechanical cell damage in the bioprinting process using a conical needle. Specifically, the cell deformation and movement during the cell-fluid interaction processes were represented by the immersed boundary method (IBM). A strain energy density (SED)-based cell damage criterion was developed and used to determine cell damage. Experiments were performed by using 3T3 fibroblasts and the results agree well with the proposed model.

Engineering complex biological structures for regenerative medicine, in vitro tissue analysis, and pharmaceutical testing require new fabrication techniques that can place specific cells in specific target locations. Conventional cell seeding methods cannot achieve this level of spatial resolution. Biofabrication is a rapidly advancing field that uses a variety of delivery mechanisms to achieve the spatial resolution necessary to place cells, biomaterials, and bioactive macromolecules in specific target locations. One new technique within this field is bioprinting, which uses drop-on-demand delivery mechanisms to fabricate biological structures. This review focuses on drop-on-demand inkjet bioprinting and provides a primer for researchers seeking to enter the field.

Biofabrication for tissue engineering and regenerative medicine is a rapidly evolving field that incorporates bioprinting or bioassembly for the development of biologically functional products with structural organization using cells, bioactive molecules, and biomaterials. Bioprinting is a biofabrication technology that utilizes biomaterials, living cells, and supporting materials, called bioink, to generate three-dimensional tissue constructs. Bioprinting offers several advantages over traditional scaffolding and microengineering methods such as precise architecture control, high reproducibility, and versatility. The ideal bioink should possess appropriate structural, mechanical, gelation, rheological, chemical, biological, degradation, and biomimetic properties for the desired application of the final product. Several natural and synthetic bioinks have been developed and this review has focused on conductive nanomaterials that have been used in combination with hydrogel materials for bioink synthesis.

This paper reviews the recent development of 3D printing of biosamples, in terms of the 3D structure design, suitable printing technology, and available materials. Successfully printed 3D biosamples should possess the properties of high cell viability, vascularization and good biocompatibility. These goals are attained by printing the materials of hydrogels, polymers and cells, with a carefully selected 3D printer from the categories of inkjet printing, extrusion printing and laser printing, based on the uniqueness, advantages and disadvantages of these technologies. For recent developments, we introduce the 3D applications of creating scaffolds, printing cells for self-assembly and testing platforms. We foresee more bio-applications of 3D printing will be developed, with the advancements on materials and 3D printing machines.

As a biomaterial, collagen has been used throughout tissue engineering and regenerative medicine. Collagen is native to the body, is highly biocompatible, and naturally promotes cell adhesion and regeneration. However, collagen fibers and the inherent weak mechanical properties of collagen hydrogels interfere with further development of collagen as a bio-ink. Herein, we demonstrate the use of a modified type-I collagen, collagen methacrylamide (CMA), as a fibril-forming bio-ink for free-form fabrication of scaffolds. Like collagen, CMA can self-assemble into a fibrillar hydrogel at physiological conditions. In contrast, CMA is photocrosslinkable and thermoreversible, and photocrosslinking eliminates thermoreversibility. Free-form fabrication of CMA was performed through self-assembly of the CMA hydrogel, photocrosslinking the structure of interest using a photomask, and cooling the entire hydrogel, which results in cold-melting of unphotocrosslinked regions. Printed hydrogels had a resolution on the order of $\sim$350$\mu$m, and can be fabricated with or without cells and maintain viability or be further processed into freeze-dried sponges, all while retaining pattern fidelity. A subcutaneous implant study confirmed the biocompatibility of CMA in comparison to collagen. Free-form fabrication of CMA allows for printing of macroscale, customized scaffolds with good pattern fidelity and can be implemented with relative ease for continued research and development of collagen-based scaffolds in tissue engineering.

The cellulose-based hydrogels have received immense interest for various biomedical applications owing to their unique structural, physico-chemical, mechanical, and biological properties. This chapter provides an overview of different cellulose-dissolving systems, cellulose derivatives, cellulose nanostructures, and cellulose-producing microorganisms, with emphasis on the fabrication, properties, and biomedical applications of cellulose-based hydrogels. Further, it highlights the current developments of the latest synthesis methods and technologies, such as 3D and 4D printing, inspired from the naturally occurring biomaterials or soft/hard tissues with numerous excellent properties, to fabricate cellulose-based hydrogels with a highly ordered microstructure, to further improve their properties and applications.

Articular cartilage is hyaline cartilage which has very limited self-repairingcapacity after its degeneration or injury. Recently, three-dimensional (3D) bioprinting provides a promising method for repair and regeneration of articular cartilage. Significant progress has been made in 3D bioprinting for cartilage regeneration, particularly in printing hydrogels in combination of cells and growth factors. In this chapter, we reviewed recent progress in cartilage 3D bioprinting, including the use of various cell sources and growth factors for cartilage formation. We also discussed the challenges and the future research directions of cartilage regeneration.