Special issue on bioinks

Catalyzed by a wider and cheaper availability of printing technology, and inspired by the design opportunities of additive manufacturing and its potential especially for the creation of three-dimensional (3D) tissue models and in regenerative medicine, the recent years have seen an unprecedented interest in the field of biofabrication. Especially due to the increase of extrusion based bioprinting, the initial lack of variability of printable cell-material formulations, so-called 'bioinks', has energized biomaterials research for various applications in biofabrication.

This special issue is dedicated to bioinks and summarizes some of the most recent developments in the field. It is headed by a proposal for a definition of the term bioink and its distinction from biomaterial inks [1]. In line with this, a review paper by Ovsianikov et al summarizes the recent activities in the field, and focuses on the important behavior of bioinks not only before and during, but also after the printing procedure [2]. A couple of articles then focus on different aspects of the assessment of printability and cell compatibility as guide for bioink development. Jüngst et al propose a step-wise rheological assessment of materials for extrusion based bioprinting, along with a mathematical model for predicting a bioprinting window for given instrumental and process parameters [3]. Malda et al present a printing protocol to assess bioink printability, with a focus on the ability of a bioink to span a distance between deposited strands of the underlying layer without sagging [4]. Heilshorn et al focus on the biological properties and present a study that proposes quantitative criteria to benchmark bioinks for cytocompatibility [5]. In a study that is dedicated to one bioink material, Bonassar et al demonstrate the effect of process conditions such as pH and cross-linking on the rheological properties and printability of collagen bioinks [6]. Similarly, Keekyoung et al focus on one of the mainly applied bioink materials, methacrylated gelatin (GelMA), and demonstrate the effects of different material sources on the rheological properties and printability [7]. Lee et al present a systematic evaluation and optimization of gelatin-alginate composite bioinks using rheological parameters [8].

A number of articles in this special issue also focus on new materials and formulation strategies for bioinks. Doo et al review an exciting and most promising trend, the use of decellularized extracellular matrix as bioink or bioink component [9]. Also inspired by natural materials but biotechnologically produced, Scheibel et al present a study on recombinant spider silk proteins with tailored properties for extrusion based bioprinting [10]. Gelinsky et al introduce a novel and generic principle to improve the mechanical properties of bioink and especially the printed constructs post-processing through nanoclay-supplementation into the bioink formulation [11]. Khadhemosseini et al present a strategy that also allows the bioprinting of cell-laden bioinks with lower viscosity, as demonstrated with different GelMA based formulations, achieved by core–shell printing where alginate is used as sheath that serves as a template to support and confine the GelMA pre-hydrogel in the core during the extrusion process, allowing for subsequent UV cross-linking [12]. Woodfield et al present a study on a new bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs [13].

This special issue also comprises studies that demonstrate the application potential of novel bioinks. Along the line of the review by Doo et al, Bertassoni et al present a dentin based bioink formulation for regenerative dentistry [14]. Kluger et al demonstrate the formation of bone-matrix in a hydroxyapatite-containing bioink formulation that is promising for the bioprinting of bone [15]. Groll et al present a study on the chondrogenesis in thiol-ene cross-linkable polyglycidol-based bioinks in a double-printing approach for cartilage bioprinting [16]. A study by Sun et al demonstrates that a novel hydroxypropyl chitin bioink allows for scalable expansion and uniform aggregation of human induced pluripotent stem cells during 3D bioprinting [17]. In a very advanced study, Mironov et al demonstrate the bioprinting of a functional vascularized mouse thyroid gland construct based on the use of cell-spheroids as crucial bioink-components and tissue building blocks [18].

These exciting examples outline the cutting edge in bioink development and highlight the breadth of this evolving field. Even though this special issue comprises many different approaches, there are many further recent trends and developments in the field, such as partial cross-linking at certain stages during the printing procedure, colloidal inks and the printing into self-healing support matrices. This underlines the ongoing activities and remaining potential for biomaterials researchers in this field. We envision that future bioinks, yet to be developed, will combine superior shape fidelity with unrestricted cytocompatibility and the intrinsic stimuli to orchestrate cellular behavior post-fabrication for desired maturation of the fabricate. It is clear that much work remains, but the initial steps have been accomplished. We are delighted to present this special issue of recent advancements toward these goals.

Completion of this comprehensive issue was possible by having a dedicated team of scholars who are internationally recognized experts in the field. We sincerely express our gratitude to all authors for their contribution to this issue. We would like to thank Drs Wei Sun and Antigoni Messaritaki for recognizing the importance of this topic in the field of biofabrication, and providing the opportunity to present an outstanding body of work in this special issue. We would also like to thank the staff at IOP Publishing for their editorial support.