Biomaterial Inks
Authors: Yu Shrike Zhang
Journal: Advanced Healthcare Materials (2020)

Three-dimensional (3D) printing has gained ever-increasing attention in the past decades since the invention of stereolithography in 1986.[1] This popularity is attributed to the unique advantages of this technology, which now is in fact a collection of various techniques including, but not limited to, those based on extrusion, inkjet, and light, that allow convenient patterning of target materials in the volumetric space in a fully or semi-automated manner. Yet it was not until more recently that the 3D printing technology was applied to medicine and biomedicine for the fabrication of medical devices and biological tissues for life quality enhancement.[2] While the 3D printing modalities are the foremost in determining our capacity in successful fabrication of volumetrically structured objects, the contributions of the materials, or what we term as “biomaterial inks”, are perhaps no less important if not more. These biomaterial inks have to be designed in such a way that they are not only specific to the desired applications, but also, allow high-fidelity 3D printing in the first place.[3] Examples range from inks that should minimize inflammatory responses of the host tissues, inks that should ensure activities of cells encapsulated or post-seeded, and/or inks that should provide multiple functionalities to mimic the sophisticated biological needs. This special issue on “Biomaterials Inks” is thus focused on biomaterials that are meticulously tailored for use as inks/bioinks towards 3D printing/bioprinting applications. We have collected three reviews, three progress reports, and ten research articles, which broadly cover the various important topics within the area. Kaplan et al. talk about directed hierarchical molecular assembly used towards biofabrication, including bioprinting, of the silk biomaterials (see article number 1901552). Moroni et al. then discuss an important class of bioinks, the dynamic bioinks taking advantages of the supramolecular and dynamic covalent chemistries, for applications in advanced bioprinting (see article number 1901798). Finally, Woodfield et al. go a step beyond and converse about the design principles of multicomponent hydrogel bioinks for extrusion bioprinting (see article number 1901648). Three systematic progress reports then ensue. An overview of recent progress in 3D bioprinting is first provided by Perriman et al., through discussions on bioprinting modality designs, tissue-specific applications, and bioink developments (see article number 1900554). Zhang et al. follow by outlining the recent advances in a specific category of 3D printing/bioprinting based on vat polymerization, detailing how biomaterial inks can be accordingly formulated and processed (see article number 2000156). Besides conventional scaffold-based tissue fabrication, scaffold-free, cell-based bioprinting is also becoming a trend, where the progress on the use of multicellular spheroids as bioinks is summarized by Murata et al. (see article number 1901831). The remainder of this special issue features ten research articles on either the designs or the applications of biomaterial inks. This embodiment of work begins with the demonstration of controlled growth factor release from digital light processing-printed hydrogels using bioinks composed of hyaluronic acid, heparin, and desired growth factors, from Chen et al. (see article number 1900977). Also using light-based bioprinting but that based on two-photon polymerization, Ovsianikov et al. show that a thiol-gelatin-norbornene bioink enabled high-definition of bioprinting of cell-laden constructs featuring long-term cellular activities (see article number 1900752). Turning the focus to extrusion bioprinting, Lim et al. report the development of a stepwise protocol for bioprinting of low-viscosity bioinks through first, time-dependent primary chemical crosslinking for viscosity enhancement, and then secondary post-bioprinting photocrosslinking for long-term shape maintenance (see article number 1901544). As is known, nutrients and oxygen play key roles in ensuring the viability and functions of bioprinted tissues – to this end, He et al. provide a strategy to bioprint alternative structures of the gelatin bioink and the gelatin methacryloyl (GelMA) bioink, where upon subsequent photocrosslinking post-bioprinting, the embedded gelatin lattice is selectively removed to expose the remaining GelMA construct to an internal network of space to enhance nutrient delivery (see article number 1901142). Built upon a completely different concept yet with a similar goal, Khademhosseini et al. design an oxygen-generating GelMA bioink that allows in situ release of oxygen from within the bioprinted cardiac tissue constructs, leading to improved viability (see article number 1901794). A cluster of research articles are centered around the bioprinting of the skeletal system, i.e., the bone and the cartilage. Gaharwar et al. suggest that by the bioprinting of scaffolds using a nanosilicate-reinforced hydrogel bioink followed by pre-conditioning with a layer of decellularized extracellular matrix on the surfaces, elevated osteogenic potential can be achieved (see article number 1901580). Levato et al. describe a dual-functionalized bioink as both cell carrier for bioprinting and cartilage-binding glue through a single-step photoactivation process (see article number 1901792). Moreover, Blunk et al. discover that supplementing bioprinted and photocrosslinked hyaluronic acid (HA) constructs with a small concentration of unmodified yet high-molecular weight HA, chondrogenic differentiation is enhanced (see article number 2000737). Toward tissue model engineering, Zhang et al. propose a stereolithographic bioprinting method to produce a tri-culture model of breast cancer invasion into the vascularized bone tissue, using respective tissue-mimicking bioink formulations (see article number 1900924). Finally, Feinberg et al. harness the freeform reversible embedding 3D printing technique and the polydimethylsiloxane ink to produce patient-specific wearable devices, which facilitate real-time measurement of vital health signals (see article number 1901735). Taken together, this collection of reviews, progress reports, and research articles in this special issue clearly illustrate the advances in our capacity to engineer biomaterial inks to enable improved and/or expanded applications of 3D printing/bioprinting in medicine and biomedicine. Nevertheless, these are only a small embodiment of the vast amount of effort underway in this exciting field, and we wish that this issue will serve as a promotor for continued innovations globally. We would further like to thank all authors for their invaluable supports that have made this special issue possible, as well as those who we have not been able to include due to the limitation on the volume. We also give our sincere appreciation to Dr. Irem Bayindir-Buchhalter for her insights in recognizing the importance of this special issue topic, and all Wiley-VCH staff for their tremendous help in the editorial process. Yu Shrike Zhang received a B.Eng. in biomedical engineering from Southeast University, China (2008), an M.S. in biomedical engineering from Washington University in St. Louis (2011), and a Ph.D. in biomedical engineering at Georgia Institute of Technology/Emory University (2013). He is currently an assistant professor at Harvard Medical School and associate bioengineer at Brigham and Women's Hospital. His research is focused on innovating medical engineering technologies, including bioprinting, organs-on-chips, microfluidics, and bioanalysis, to recreate functional tissues and their biomimetic models towards applications in precision medicine.