Hydrogel-based Devices Research Articles

Programmable Reversible Shape Transformation of Hydrogels Based on Transient Structural Anisotropy.

Stimuli-responsive shape-transforming hydrogels have shown great potential toward various engineering applications including soft robotics and microfluidics. Despite significant progress in designing hydrogels with ever more sophisticated shape-morphing behaviors, an ultimate goal yet to be fulfilled is programmable reversible shape transformation. It is reported here that transient structural anisotropy can be programmed into copolymer hydrogels of N-isopropylacrylamide and stearyl acrylate. Structural anisotropy arises from the deformed hydrophobic domains of the stearyl groups after thermomechanical programming, which serves as a template for the reversible globule-to-coil transition of the poly(N-isopropylacrylamide) chains. The structural anisotropy is transient and can be erased upon cooling. This allows repeated programming for reversible shape transformation, an unknown feature for the current hydrogels. The programmable reversible transformation is expected to greatly extend the technical scope for hydrogel-based devices.

Engineering a Porous Hydrogel-Based Device for Cell Transplantation.

Islet cell transplantation in encapsulation devices provides a potential means of treatment for type 1 diabetes. However, such devices pose challenges that must be addressed. Most current encapsulating devices are not scalable and lack retrievability which limit their potential clinical applications. Here, a translatable cell encapsulation device, which is porous, flexible, scalable, and retrievable, is reported. The device is fabricated from processable tough hydrogels (water content >400%), which are extremely tough (>1000 J m-2), yet soft (modulus ∼250-1000 kPa), and highly stretchable (up to 1000%). A facile method is introduced to render hydrogels porous (up to 60%) and control their pore size (∼150-600 μm). Human insulin-producing pancreatic β-cell lines and porcine neonatal islet cell clusters are incorporated into the pores of the tough hydrogel device with in vitro biocompatibility studies revealing no cytotoxic effects. Viability staining, insulin protein expression, and in vitro glucose-stimulated insulin secretion of the encapsulated β-cell lines and islets indicate high viability and desired metabolic and endocrine function. Our findings provide a proof-of-concept for the scalable manufacturing of retrievable, hydrogel-based devices with porous structures to facilitate the transplantation of cells without interfering with the cells' function.

Hydrogels for cancer drug delivery

Developing the assurance and potency proportion of actual chemotherapeutic medicament is an ongoing task that needs to be worked upon hand in hand with development of new chemotherapeutics agents that require a great deal of time and cost. Hydrogels have emerged as promising drug delivery systems which can efficiently provide both contiguous and sensual control over the discharge of numerous therapeutics. They have also found use in contact lens manufacture, cosmetics, hygienic products, wound healing. In addition to facilitating building up organoids and organ on a chip of hydrogels have thus become an important issue as drug delivery systems for chemotherapeutics. This review emphasis on the mechanisms of hydrogels, mechanism of hydrogel formation, their types and applications of various hydrogels as a delivery system for chemotherapeutic agent. Studies had made tremendous advances in reconstruction of the tumor form, tumor treatment and related therapies due to the special properties of hydrogels. Notably, it is possible to adjust hydrogel-based devices to react to internal stimuli specific to cancer. Such well-known medicament storage is adopted as intelligent transports for various cargoes, namely chemotherapeutics, genes, and radioisotopes, both bare and nanoparticle-encapsulated. Hydrogels can provide spatial and temporal influence over the discharge of several biomedical products, along with medicines for small molecules, macromolecular drugs and cells.

Dispersed Association of Single-Component Short-Alkyl Chains toward Thermally Programmable and Malleable Multiple-Shape Hydrogel.

In pursuit of intelligent hydrogel-based devices, it is imperative to concurrently enhance the shape programmability and customization of hydrogels in order to realize sophisticated actuation and implantation. Until now, multiple temporary shapeshifting of hydrogels has required either multiple external stimuli or distinct thermal-transition phases. In addition, reprocessing the permanent shape of hydrogel mostly relies on the change in their components. These complex prerequisites present challenges to programmability and customization of application-related shapes for hydrogels. This paper reports a type of thermally programmable and malleable multiple-shape hydrogel. The network of this hydrogel is solely composed of a type of polyvinyl alcohol derivative, which is synthesized by substituting hydroxyl groups of polyvinyl alcohol with single-component octyl chains. Through water-vapor exchange and heating in water, these single-component octyl side chains form dispersed clusters with a large strength gradient. Such broadly dispersed clusters serve as switchable segments and dynamic net-points to orthotopically offer multiple (e.g., quintuple) temporary shapes and editable permanent shapes, respectively, thereby realizing sophisticated and designed shape changes. This hydrogel system can act as a smart device for on-demand bidirectional twining around a 1D substrate. Such a capability potentially enables the self-mounting and self-detaching behavior of soft devices on tissues with minimal invasion.

Nanoparticle-Polymer Synergies in Nanocomposite Hydrogels: From Design to Application.

Hydrogels are an important class of soft materials with high water retention that exhibit intelligent and elastic properties and have promising applications in the fields of biomaterials, soft machines, and artificial tissue. However, the low mechanical strength and limited functions of traditional chemically cross-linked hydrogels restrict their further applications. Natural materials that consist of stiff and soft components exhibit high mechanical strength and functionality. Among artificial soft materials, nanocomposite hydrogels are analogous to these natural materials because of the synergistic effects of nanoparticle (NP) polymers in hydrogels construction. In this article, the structural design and properties of nanocomposite hydrogels are summarized. Furthermore, along with the development of nanocomposite hydrogel-based devices, the shaping and potential applications of hydrogel devices in recent years are highlighted. The influence of the interactions between NPs and polymers on the dispersion as well as the structural stability of nanocomposite hydrogels is discussed, and the novel stimuli-responsive properties induced by the synergies between functional NPs and polymeric networks are reviewed. Finally, recent progress in the preparation and applications of nanocomposite hydrogels is highlighted. Interest in this field is growing, and the future and prospects of nanocomposite hydrogels are also reviewed.

Thermal Transport in Soft PAAm Hydrogels.

As the interface between human and machine becomes blurred, hydrogel incorporated electronics and devices have emerged to be a new class of flexible/stretchable electronic and ionic devices due to their extraordinary properties, such as softness, mechanically robustness, and biocompatibility. However, heat dissipation in these devices could be a critical issue and remains unexplored. Here, we report the experimental measurements and equilibrium molecular dynamics simulations of thermal conduction in polyacrylamide (PAAm) hydrogels. The thermal conductivity of PAAm hydrogels can be modulated by both the effective crosslinking density and water content in hydrogels. The effective crosslinking density dependent thermal conductivity in hydrogels varies from 0.33 to 0.51 Wm−1K−1, giving a 54% enhancement. We attribute the crosslinking effect to the competition between the increased conduction pathways and the enhanced phonon scattering effect. Moreover, water content can act as filler in polymers which leads to nearly 40% enhancement in thermal conductivity in PAAm hydrogels with water content vary from 23 to 88 wt %. Furthermore, we find the thermal conductivity of PAAm hydrogel is insensitive to temperature in the range of 25–40 °C. Our study offers fundamental understanding of thermal transport in soft materials and provides design guidance for hydrogel-based devices.

Hydrophobic Hydrogels: Toward Construction of Floating (Bio)microdevices

Hydrogels, formed through cross-linking of hydrophilic polymer chains, represent a class of materials that are capable of holding large volumes of water. Here we report a novel class of hydrophobic hydrogels that can free-float on the surface of different aqueous media by coating conventional hydrogels with a layer of hydrophobic microparticles. We further demonstrate that these floating hydrogel-based devices can be used for sensing applications on liquid surfaces such as the construction of floating pH meters. Moreover, we demonstrate that the floating hydrogels present high mobility with excellent self-assembling property on the surface of water. Importantly, the floating systems reserved the intrinsic biocompatibility of the core hydrogels, enabling microengineering of floating tissue constructs. It is expected that these floating hydrophobic hydrogel-based devices will likely find widespread applications including but not limited to sensing, tissue engineering, and biomedicine.

From 3D Hierarchical Scaffolds for Tissue Engineering to Advanced Hydrogel-Based and Complex Devices for in situ Cell or Drug Release

In the past few years, researchers have focused on the development of three-dimensional (3D) advanced scaffolds and multifunctional hydrogel-based materials.As reported in literature, 3D polymer-based composite scaffolds for tissue engineering have been manufactured through conventional and advanced manufacturing techniques, and different injectable materials and hydrogel-based systems have been proposed and studied.The aim of the current research was to define an approach in the development of multifunctional tools spanning from 3D hierarchical scaffolds for soft tissue engineering to advanced hydrogel-based devices for in situ cell or drug release. The mechanical/rheological behaviour as well as the structural/functional features of the designed devices were discussed and analyzed.

2G45 ハイドロゲルを基板とする伸縮性電極シートの開発と生体応用

Hydrogel-based, molecular permeable electronic devices are considered to be promising for electrical stimulation and recording of living tissues, either in vivo or in vitro. This study reports the fabrication of the hydrogel-based devices that remain highly electrically conductive under substantial stretch and bending. Using a simple technique involving a combination of chemical polymerization and electropolymerization of poly (3,4-ethylenedioxythiophene) (PEDOT), a tight bonding of a conductive composite of PEDOT and polyurethane (PU) to an elastic double-network hydrogel is achieved to make fully organic PEDOT/PU-hydrogel hybrids. Their response to repeated mechanical stretching, hydration-drying cycles, and autoclaving is assessed, demonstrating excellent stability, without any mechanical or electrical damage. The adhesion, proliferation, and differentiation of neural and muscle cells cultured on these hybrids are demonstrated, advancing the field of tissue engineering with integrated electronics.

Highly conductive stretchable and biocompatible electrode-hydrogel hybrids for advanced tissue engineering.

Hydrogel-based, molecular permeable electronic devices are considered to be promising for electrical stimulation and recording of living tissues, either in vivo or in vitro. This study reports the fabrication of the first hydrogel-based devices that remain highly electrically conductive under substantial stretch and bending. Using a simple technique involving a combination of chemical polymerization and electropolymerization of poly (3,4-ethylenedioxythiophene) (PEDOT), a tight bonding of a conductive composite of PEDOT and polyurethane (PU) to an elastic double-network hydrogel is achieved to make fully organic PEDOT/PU-hydrogel hybrids. Their response to repeated bending, mechanical stretching, hydration-dessication cycles, storage in aqueous condition for up to 6 months, and autoclaving is assessed, demonstrating excellent stability, without any mechanical or electrical damage. The hybrids exhibit a high electrical conductivity of up to 120 S cm(-1) at 100% elongation. The adhesion, proliferation, and differentiation of neural and muscle cells cultured on these hybrids are demonstrated, as well as the fabrication of 3D hybrids, advancing the field of tissue engineering with integrated electronics.

Rapid and accurate generation of various concentration gradients using polydimethylsiloxane-sealed hydrogel device

We report a microfluidic device that can rapidly and accurately generate various concentration gradients in a controllable manner for the chemotaxis study of motile bacterial cells by integrating hydrogel into polydimethylsiloxane (PDMS) microchannels. We performed numerical simulations for both the PDMS-sealed hydrogel hybrid device and a representative conventional hydrogel-based device to theoretically compare their characteristics. In addition, we experimentally demonstrated that the PDMS-sealed hydrogel device not only produces various linear and nonlinear concentration gradients without flow-induced shear stresses on motile bacterial cells but also exhibits remarkable advantages over conventional hydrogel-based devices. For example, the PDMS-sealed hydrogel device can be used for fast and accurate generation of various concentration gradients, prevents dehydration of hydrogel and evaporation of solutions, directs diffusion of chemicals such as chemoattractants, exhibits long-term durability, and is easy to handle. Because the hydrogel used is biocompatible and arbitrary concentration profiles can be easily designed and produced on a chip, we believe that not only the PDMS-sealed hydrogel fabrication method but also the versatile concentration gradient generation device can be used for various studies on interaction between chemicals and cells including bacterial chemotaxis assays.

Histomorphology of thrombus organization, neointima formation, and foreign body response in retrieved human aneurysms treated with hydrocoil devices

Biological processes, such as thrombus organization, endothelialization, and foreign body response, that occur following embolization of intracranial aneurysms are poorly understood. We examined 13 human aneurysms (retrieved at autopsy 1-74 days postembolization) treated with hybrid hydrogel-platinum coil devices and platinum coils. The specimens were embedded in methyl methacrylate and ground sections were surface stained. Using light microscopy, thrombus organization in the sac, endothelialization of the neck, and foreign body response to the embolic devices were determined. The area percentages of the sac occupied by embolic devices and unorganized thrombus were quantified using image analysis. Thrombus organization increased over time, but was incomplete up to 74 days post-treatment. Neointima formation had started at 5 days upon dense fibrin depositions and progressed to form a new vessel wall at 74 days. The foreign body response to the hydrogel was characterized by mononuclear macrophages, while platinum coils were surrounded by multinuclear foreign body giant cells. Histometric aneurysm occlusion ranged from 89 to 100% and embolic devices occupied 31-64% of the aneurysm sac. These findings showed that the hydrogel-based devices occupied a large percentage of the aneurysm sac, provided a framework for thrombus organization to occur, and elicited less severe foreign body response than platinum coils.

Bridges between two worlds

This review paper presents hydrogel-based devices for biomedical applications. The first part of the paper gives a comprehensive, qualitative, theoretical overview of hydrogels’ synthesis and operation. Crosslinking methods, operation principles and transduction mechanisms are discussed in this part. The second part includes applications of hydrogel devices in specific fields of interest. Sensing, fluid control, drug delivery, nerve regeneration and other biomedical applications constitute the main focus of this part. The aim of this paper is to briefly present recent advances of the field, without neglecting older ones, and to discuss important or novel concepts of each

A nanoscale drug-entrapment strategy for hydrogel-based systems for the delivery of poorly soluble drugs

The hydrophilic nature of hydrogel matrices makes them disadvantageous to entrap poorly soluble therapeutic agents and greatly restricts their applications as drug-delivery systems. In this study, we demonstrated that sustained delivery of lipophilic drugs in hydrogel-based devices can be readily achieved by enhancing retention of drugs within micelles. This nanoscale drug-entrapment strategy was applied to develop a polymeric drug-eluting stent. Sirolimus, a lipophilic anti-proliferative/immunosuppressive drug, was entrapped into the hydrophobic core of Pluronic L121 micelles and then blended in a chitosan-based strip and crosslinked by an epoxy compound to fabricate test stents. It was found that the use of such a nanoscale drug-entrapment strategy was able to significantly increase the loading efficiency of lipophilic drugs, prevent the drug from aggregation and beneficially reduce its initial burst release; thus, the duration of drug release was extended considerably. When implanting the stent in rabbit infrarenal abdominal aortas, in-stent restenosis was markedly reduced and less inflammatory reaction was observed, while unfavorable effects such as delayed endothelial healing caused by the overdose of sirolimus could be significantly evaded.

Mathematical model for the prediction of the overall profile of in vitro solute release from polymer networks

The loading of solutes onto and their release from hydrogel-based devices can be better understood when they are treated as a partition phenomenon. Partition activity ( α) is a parameter that determines the existence of partition phenomena. It expresses the physical chemical affinities of the solute between the solvent and hydrogel phases. When α = 0 , there is no release of the solute from the hydrogel; however, if α > 0 , there is partitioning of the solute between the solvent and the hydrogel phases, and release of the solute from the hydrogel can be observed. The mathematic model proposed here predicts the overall release profile of vitamin B 12, methylene blue (MB), and acid orange 7 (AO) from semi-interpenetrating network (semi-IPN) hydrogels composed of PNIPAAm and PAAm. Experimental release tests demonstrated that alterations on variables of the system change both the released fraction and the release rate of such solutes, confirmed by the changes on values of α (an equilibrium parameter) and k R (an kinetic parameter). The modeling of solute release describes the α effects on release of the solute from polymer networks. The solute release mechanism is viewed here as a diffusional transport process and as a partition phenomenon. The partitioning of the solutes occurs between the solvent phase and the hydrogel phase, and the possible physical chemical affinities of the solute between hydrogel and solvent are considered.

Mechanically adjustable chemostats based on stimuli-responsive polymers

A method for a mechanical operating point adjustment of hydrogel-based devices performing closed loop control has been developed. These so-called chemostats automatically control certain chemical and energy-based conditions of a liquid. The adjustment of the controlled condition is provided by a defined change of the triggering point by the activation unit of the device and the hydrogel actuator determining the basic functional relationship. The antagonistic principles of automatic valve chemostats were introduced, which can alternatively realize a normally open or a normally closed function. Using the hydrogel poly(N-isopropylacrylamide) the chemostat's switching concentration of ethanol in aqueous solution can be adjusted in the range of 5 and 20wt.% with a practically relevant precision of 1wt.%. The controllability of an energy-based condition by the chemostat was investigated on the process temperature control. We found that this temperature can be mechanically adjusted in a range of 25 and 35°C with a standard deviation below 0.75K.

Is there a future in glucose-sensitive, responsive insulin delivery systems?

Considerable amount of work has been directed towards the development of optimal glucose-responsive devices for insulin release. Hydrogel-based devices offer a wide range of parameters that can be tuned to obtain easy control of the insulin release properties. Taking advantage of their unique swelling and release properties, we may be able to achieve the desirable steady state and dynamic nature of insulin release. We review previous attempts at developing glucose oxidase-based insulin delivery systems, and we conclude that there are significant problems that must be solved for an adequate development of a device for treatment of diabetics.