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The field of biofabrication has seen tremendous advances in the past decade. More recently, the emerging role of biofabrication in allowing faithful generation of models of human tissues in their healthy and diseased states has been demonstrated and has rapidly expanded. These biomimetic models are potentially widely applicable in a range of research and translational areas including but not limited to fundamental biology studies as well as screening of chemical compounds, such as therapeutic agents. The United States Food and Drug Administration Modernization Act 2.0, which now no longer requires animal tests before approving human drug trials, will likely further boost the field in the years to come. This Special Issue, with a collection of 11 excellent research articles, thus focuses on showcasing the latest developments of biofabrication towards human disease modeling, spanning from 3D (bo)printing to organ-on-a-chip as well as their integration., (Creative Commons Attribution license.)

Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMA LOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we briefly introduce the current state of knowledge regarding macrophage function and nomenclature. Next, we discuss the use of controlled release strategies to tune the balance between the M1 and M2 phenotypes in the context of tissue engineering applications. We discuss recent literature related to the release of anti-inflammatory molecules (including nucleic acids) and the sequential release of cytokines to promote a timely M1-M2 shift. In addition, we describe the use of macrophages as controlled release agents upon stimulation by physical and/or mechanical cues provided by scaffolds. Moreover, we discuss current and future applications of "smart" implantable scaffolds capable of controlling the cascade of biochemical events related to healing and vascularization. Finally, we provide our opinion on the current challenges and the future research directions to improve our understanding of the M1-M2 macrophage balance and properly exploit it in tissue engineering and regenerative medicine applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of tissue engineering applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental cell research, cell signaling, drug and gene delivery, and bio-sensing.

Increasing expansion rate in cell manufacturing systems would allow faster delivery of life-saving treatments to a greater number of patients. Chaotic printing is a novel biofabrication technology that could improve cell expansion capabilities by producing hydrogel filaments layered with open channels, resulting in significantly higher surface area-per-unit-volume of interface between cells and nutrient media compared to existing systems. In this study, we chaotically printed hydrogel filaments laden with clinically-relevant, bone marrow-derived human mesenchymal stem cells. After the first week of a 21-day expansion period, cell-laden hydrogel filaments containing open channels had an optimal expansion rate and 2.1x as many cells as filaments without channels. We then validated a novel bioreactor design for expanding cells under flowing nutrient media conditions. [ABSTRACT FROM AUTHOR]

The micropatterning of thin films represents a challenging task, even for additive manufacturing techniques. In this work, we introduce the use of inkjet-printing technology coupled with a gas-foaming process, to produce patterned porosities on polymeric thin films, to develop a bubble-writing method. Inkjet printing of an aqueous solution of poly (vinyl alcohol) (PVA), a well-known gas-barrier polymer, allows the selective coating of a thin poly (lactic acid) (PLA) film, which is, successively, exposed to a gas-foaming process. The foaming of the thin PLA film is effective, only when PVA is printed on top, since the PVA barrier hinders the premature loss of the gas, thus allowing the formation of cavities (bubbles) in the covered areas; then, removing the PVA coating by water washing forms a bubble pattern. As a proof of concept, the surface-morphology features of the patterned porous PLA films have been proven effective at driving endothelial cell growth. A new technological platform is, hence, introduced in the field of tissue engineering and, in general, in fields involving thin films, where a patterned porous structure may add value. [ABSTRACT FROM AUTHOR]