Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.

/pdf/25th-anniversary-article-rational-design-and-applications-of-4vstyfvewj.pdf

25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

Organ Printing: Tissue Spheroids as Building Blocks

With much advancement in the field of nanotechnology, bioengineering, and synthetic biology over the past decade, microscales and nanoscales devices are becoming a reality. Yet the problem of engineering a reliable communication system between tiny devices is still an open problem. At the same time, despite the prevalence of radio communication, there are still areas where traditional electromagnetic waves find it difficult or expensive to reach. Points of interest in industry, cities, and medical applications often lie in embedded and entrenched areas, accessible only by ventricles at scales too small for conventional radio waves and microwaves, or they are located in such a way that directional high frequency systems are ineffective. Inspired by nature, one solution to these problems is molecular communication (MC), where chemical signals are used to transfer information. Although biologists have studied MC for decades, it has only been researched for roughly 10 year from a communication engineering lens. Significant number of papers have been published to date, but owing to the need for interdisciplinary work, much of the results are preliminary. In this survey, the recent advancements in the field of MC engineering are highlighted. First, the biological, chemical, and physical processes used by an MC system are discussed. This includes different components of the MC transmitter and receiver, as well as the propagation and transport mechanisms. Then, a comprehensive survey of some of the recent works on MC through a communication engineering lens is provided. The survey ends with a technology readiness analysis of MC and future research directions.

/pdf/a-comprehensive-survey-of-recent-advancements-in-molecular-2pjzig1xwb.pdf

A Comprehensive Survey of Recent Advancements in Molecular Communication

Direct 3D bioprinting of perfusable vascular constructs using a blend bioink

A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented. The technique incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures. The extrusion system is then coupled to a microfluidic device to control the bioink arrangement deposition, demonstrating the versatility of the bioprinting technique. This low-viscosity cell-responsive bioink promotes cell migration and alignment within each fiber organizing the encapsulated cells.

/pdf/microfluidic-bioprinting-of-heterogeneous-3d-tissue-1ngcuqylpr.pdf

Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low-Viscosity Bioink.

Artificial reconstruction of fibre-shaped cellular constructs could greatly contribute to tissue assembly in vitro. Here we show that, by using a microfluidic device with double-coaxial laminar flow, metre-long core-shell hydrogel microfibres encapsulating ECM proteins and differentiated cells or somatic stem cells can be fabricated, and that the microfibres reconstitute intrinsic morphologies and functions of living tissues. We also show that these functional fibres can be assembled, by weaving and reeling, into macroscopic cellular structures with various spatial patterns. Moreover, fibres encapsulating primary pancreatic islet cells and transplanted through a microcatheter into the subrenal capsular space of diabetic mice normalized blood glucose concentrations for about two weeks. These microfibres may find use as templates for the reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood vessels or nerve networks in vivo.

Metre-long cell-laden microfibres exhibit tissue morphologies and functions

We aimed to create an autonomous on-chip system that performs targeted delivery of lipid vesicles (liposomes) as nano- or microscale reactors using machinery from biological systems. Reactor-liposomes would be ideal model cargoes to realize biomolecular-motor-based biochemical analysis chips; however, there are no existing systems that enable targeted delivery of cargo-liposomes in an autonomous manner. By exploiting biomolecular-motor-based motility and DNA hybridization, we demonstrate that single-stranded DNA (ssDNA)-labeled microtubules (MTs), gliding on kinesin-coated surfaces, acted as cargo transporters and that ssDNA-labeled cargo-liposomes were loaded/unloaded onto/from gliding MTs without bursting at loading reservoirs/micropatterned unloading sites specified by DNA base sequences. Our results contribute to the development of an alternative strategy to pressure-driven or electrokinetic flow-based microfluidic devices.

Biomolecular-motor-based autonomous delivery of lipid vesicles as nano- or microscale reactors on a chip

We aimed to create autonomous on-chip systems that perform targeted translocations of nano- or microscale particles in parallel using machinery that mimics biological systems. By exploiting biomolecular-motor-based motility and DNA hybridization, we demonstrate that single-stranded DNA-labeled microtubules gliding on kinesin-coated surfaces acted as cargo translocators and that single-stranded DNA-labeled cargoes were loaded/unloaded onto/from gliding microtubules at micropatterned loading/unloading sites specified by DNA base sequences. Our results will help to create autonomous molecular sorters and sensors.

Biomolecular-motor-based nano- or microscale particle translocations on DNA microarrays.

This paper describes core-shell hydrogel wires for constructing 3D heterogeneous hydrogel microstructures containing biomaterials. A core hydrogel layer contains biomaterials such as cells, and a shell hydrogel layer covers the core to realize a mechanically-robust hydrogel wire. Using this core-shell gel wires, we demonstrate a woven sheet with heterogeneous gel wires by using our stereolithographically-made weaving machine. We also fabricate a reeled-up tube-like cell-containing structure by a glass tube spindle, inspired by tools from fiber industry. We show that our core-shell gel wires and weaving methods are powerful approach to arrange heterogeneous biomaterials in three dimensions.

Core-shell gel wires for the construction of large area heterogeneous structures with biomaterials

Microfibers which comprises micro gel fibers composed of a collagen gel and has improved mechanical strength, wherein the micro gel fibers are coated with a high-strength hydrogel such as an alginate gel.

Riho Gojo

Papers

Metre-long cell-laden microfibres exhibit tissue morphologies and functions

Biomolecular-motor-based autonomous delivery of lipid vesicles as nano- or microscale reactors on a chip

Biomolecular-motor-based nano- or microscale particle translocations on DNA microarrays.

Core-shell gel wires for the construction of large area heterogeneous structures with biomaterials

Coated micro gel fibers