Deformable Hydrogel Research Articles

Modeling Mass Transport Dynamics in Deformable Hydrogels during Evaporation.

Hydrogels possess exceptional mechanical properties and biocompatibility, making them widely used in contemporary bioengineering. Specifically, in the development of wearable and implantable health monitoring devices as well as drug delivery systems, hydrogels are utilized to enable precise control over the transport of solutes. Nonetheless, predicting the distribution of substances within hydrogels still poses a significant challenge due to the complex interplay between the movement of water content, migration of solutes, and deformability of the hydrogel polymer network, which presents challenges to theoretical modeling. Our work introduces a numerical model that addresses the movement of water and solute within a flexible hydrogel, accounting for evaporation and/or moisture absorption at the boundary. The model solves for water saturation, solute concentration, and hydrogel deformation iteratively at each time step while computing the boundary movement velocity based on the transport process. By comparing the modeled results of geometry deformation and water and solute distributions during evaporation with our experiments, we demonstrate the accuracy and applicability of our proposed model. This capability to precisely analyze water and solute concentrations in deformable and nonuniform hydrogel environments paves the way for advancements in biosensing and drug delivery methods that rely on elastic porous materials.

β2 integrins impose a mechanical checkpoint on macrophage phagocytosis

Phagocytosis is an intensely physical process that depends on the mechanical properties of both the phagocytic cell and its chosen target. Here, we employed differentially deformable hydrogel microparticles to examine the role of cargo rigidity in the regulation of phagocytosis by macrophages. Whereas stiff cargos elicited canonical phagocytic cup formation and rapid engulfment, soft cargos induced an architecturally distinct response, characterized by filamentous actin protrusions at the center of the contact site, slower cup advancement, and frequent phagocytic stalling. Using phosphoproteomics, we identified β2 integrins as critical mediators of this mechanically regulated phagocytic switch. Macrophages lacking β2 integrins or their downstream effectors, Talin1 and Vinculin, exhibited specific defects in phagocytic cup architecture and selective suppression of stiff cargo uptake. We conclude that integrin signaling serves as a mechanical checkpoint during phagocytosis to pair cargo rigidity to the appropriate mode of engulfment.

Time-space regulating prodrug hydrogels for prevention of peritendinous adhesion

The bidirectional regulations of antiadhesion and regeneration are crucial for Achilles tendon injuries. However, the precise prevention and treatments of peritendinous adhesions both in time and space are still great challenges. Here, a series of time–space regulating prodrug (tannic acid (TA), epigallocatechin (EGC) and epigallocatechin gallate (EGCG)) hydrogels are designed for the prevention of peritendinous adhesion in Achilles tendon contusion and rupture injuries. In the term of space, the self-healing and deformable hydrogels prepared by crosslinking phenylboric acid (PBA) functionalized polyphosphazene (PZBA) with guar gum (GG) through ROS-responsive phenylborate ester (PBAE) can specifically aggregate to the high ROS sites via the ROS-responsive degradation and recombination of PBAE. Thus, providing support and acting as barriers to inhibit fibroblast proliferation. In the term of time, the prodrug strategy using ROS-responsive PBAE as bridging linker can achieve long-term anti-inflammatory effect over 2 weeks. Furthermore, the degradation time of hydrogels matched the course of peritendinous adhesion, thus achieved bidirectional regulations (decrease the gene expression of TGF-β1, COL-1 and COL-3 to antiadhesion in the early stage but increase them to promote regeneration in the late stage). This study presents a promising approach employing smart prodrug hydrogels with time–space regulating properties for prevention of peritendinous adhesion.

A bionic mimosa soft robot based on a multi-responsive PNIPAM-PEGDA hydrogel composition.

Deformation plays a vital role in the survival of natural organisms. One example is that plants deform themselves to face the sun for sufficient sunlight exposure, which allows them to produce nutrients through photosynthesis. Drawing inspiration from nature, researchers have been exploring the development of 3D deformable materials. However, the traditional approach to manufacturing deformable hydrogels relies on complex technology, which limits their potential applications. In this study, we simulate the stress variations observed in the plant tissue to create a 3D structure from a 2D material. Using UV curing technology, we create a single-layer poly(N-isopropylacrylamide) hydrogel sheet with microchannels that exhibit distinct swelling rates when subjected to stimulation. After a two-step curing process, we produce a poly(N-isopropylacrylamide)-polyethylene glycol diacrylatedouble-layer structure that can be manipulated to change its shape by controlling the light and solvent content. Based on the double-layer structure, we fabricate a dual-response driven bionic mimosa robot that can perform a variety of functions. This soft robot can not only reversibly change its shape but also maintain a specific shape without continuous stimulation. Its capacity for reversible deformation, resulting from internal stress, presents promising application prospects in the biomedical and soft robotics domain. This study delivers an insightful framework for the development of programmable soft materials.

Electrosteric, van der Waals and elastic interaction of polyelectrolyte hydrogels

The electrosteric interaction energy for a charged hydrogel and hard plane, and between two charged hydrogels is derived in the Debye–Hückel approximation. This is combined with a van der Waals potential that explicitly addresses the Hamaker constant for the solvent-mediated hydrogel interactions. Then, in the Derjaguin approximation, DLVO-type interaction potentials are provided for hydrogel and hard/rigid spheres, accounting for elastic deformation that accompanies adhesion. As examples, this furnishes the energy for cohesion of soft polyelectrolyte microspheres, and provides a quantitative interpretation for the adhesion of rigid latex spheres to a soft deformable hydrogel, as reported by Sato et al. (Sato et al. 2017 Sci. Rep. 7 , 1–10 ( doi:10.1038/s41598-017-06257-1 )). The theory demonstrates that weak van der Waals attraction of hydrogels is readily balanced by electrosteric interactions, e.g. making colloidal hydrogel dispersions less stable than their rigid-particulate counterparts.

Investigating the relationship between cytotoxic T lymphocyte mechanical output and metabolism.

In order to execute their cytolytic functions, cytotoxic T lymphocytes (CTLs) must first migrate into the peripheral tissues and then form immune synapses (IS) on target antigen-presenting cells. Both migration and IS formation involve mechanical force generation that is sustained by actin cytoskeletal rearrangement, a dynamic process of polymerizing G-actin monomers into F-actin filaments. Actin dynamics are important for generating structures such as the lamellipodia of migrating cells, the microvilli and mobile signalsomes at the IS, as well as synaptic pushing-and-pulling forces that have been implicated in maximizing cytolytic efficiency. However, little is known of the energy sources that fuel such mechanical activities. Actin dynamics are expected to be energetically demanding, given that actin is an ATPase and each G-actin hydrolyzes one ATP during assembly into filaments. In this study, we observed CTLs migrating and forming IS under various metabolic stresses. We discovered that during long-term migration, CTLs utilize nutrients in the environment, as real-time exchange of media into salt solutions within a perfusion chamber led to cells slowing down significantly. To measure force exertion at the IS, CTLs were treated with various inhibitors of metabolic pathways while forming synapses against deformable hydrogel balls. Using a custom computational pipeline, we found that synaptic forces depend on multiple metabolic pathways such as glycolysis and oxidative phosphorylation. Our study highlights a hitherto unexplored connection between cellular metabolism and mechanical activities integral to T-cell function and immune protection. This is of particular interest in the context of T-cell exhaustion, whereby CTLs chronically stimulated in metabolically inhospitable environments, such as tumors, develop into hypofunctional exhausted T cells. We suspect that immune hypo-functionality in these contexts may also involve defects in migration and IS formation due to the metabolic demand of these mechanical activities.

Shape deformable hydrogels prepared by altering surface areas with scratching and photolithography patterning methods

Shape deformations of hydrogels are achieved by changing the surface areas of isotropic hydrogels with simple, facile and efficient scratching and photolithography patterning methods.

Droplet lift-off from hydrophobic surfaces from impact with soft-hydrogel spheres

Droplet impacts on superhydrophobic surfaces may result in complete bouncing, with the absence of contact hysteresis and viscous dissipation leading the droplet to fully rebound off the surface. This rebound usually happens in the retraction phase, when the droplet retracts back after reaching a maximum spread diameter. Here, we present experimental evidence of a bouncing phenomenon where a sessile droplet on a hydrophobic surface bounces off the surface in its spreading phase when a soft deformable hydrogel sphere axisymmetrically impacts the droplet. We term this as ‘Lift-Off’ and propose a simple force balance based on the deformation characteristics of the hydrogel sphere to explain the out-of-plane jump of the droplet during spreading. We observe three different impact regimes, and propose their dependency on a modified elastic ‘Mach’ number (Ma*) with Ma* ≈ 0.1 corresponding to the onset of lift-off. We also report on the unique acoustic signatures of lift-off cases, associated with the capture of air-bubbles through the air-borne retracting droplet rim. These results may have potential applications for drainage and surface cleaning, non-stick surface coating, industrial mixing and plant disease spreading.

Wnt3a loaded deformable hydrogel acts as a 3D culture platform for in situ recruitment of stem cells to efficiently repair bone defects via the asymmetric division

Biomaterial-based tissue engineering has emerged as a hotspot in the field of osteanagenesis. Due to invasive operation in the transplantation process always bring irreparable damage to patients, approaches that enable innate repair mechanisms hold considerable promise for bone repair. To this end, a rational design based on in situ recruitment of stem cells is proposed to circumvent the troublesome problem. In this study, an interpenetration network hydrogel is developed utilizing chitosan (CS), in which the enriched bone marrow mesenchymal stem cells (BMSCs) can undergo a tridimensional and freely proliferation. Moreover, the encapsulation of biological growth factor Wnt3a promotes the differentiation of osteoprogenitor cells with an asymmetric cell divisions (ACD) manner, thereby accelerating bone formation. With this “smart biomaterials”, a robust instant stem cell ingrowth within the deformable hydrogel and a high efficiency of bone regeneration on a murine skull are observed, both of which are vital for clinical applications. Such an osteoinductive system represents the advanced design concept to repair bone defects effectively, and offers a promising strategy for the development of future bone tissue engineering.

Rapid Preparation of Dual Cross-Linked Mechanical Strengthening Hydrogels via Frontal Polymerization for use as Shape Deformable Actuators

The hydrogel artificial muscle has demonstrated enormous potential in various applications, such as soft robotics and actuators. However, the poor mechanical properties have always limited the practical applications of hydrogels. Here, we designed a Zr4+ coordinated and vinyl hybrid silica nanoparticle (VSNP) grafted poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid) (VSNP@poly(AM-co-AMPS)-Zr4+) via frontal polymerization (FP). Benefiting from the synergistic effect of the polymer–nanocomposite interaction (VSNP nanocomposite) and metal ion–ligand interactions (Zr4+–sulfonate group coordination), the mechanical properties of hydrogels can be extremely improved. In addition, a deformable hydrogel with gradient structure and swelling ratio was designed through introducing Zr4+ to one side of the hydrogel, which can serve as an artificial muscle to accomplish multiple moving activities, such as bending and grabbing. This work offers an easy-to-perform strategy to construct mechanically strong hydrogels, which might promote the development of artificial muscle materials.

Solvent-responsive strong hydrogel with programmable deformation and reversible shape memory for load-carrying soft robot

The development of shape deformation hydrogels has aroused interests of their immense applications in diverse fields such as actuators, soft robotics, and artificial muscles. However, the existing deformable hydrogels can hardly meet the requirements of facile preparation, excellent mechanical properties and reversible shape memory, which greatly limits their further applications. In this work, a new type of fully physically cross-linked deformable hydrogel with mechanically strong, tough, stretchable, and solvent-responsive property is fabricated via free radical polymerization at room temperature, followed by immersed in a Fe3+ aqueous solution. The strong physical interactions of polyacrylic acid (PAA)-Fe3+ metal complexation and hydrogen bond endowed this hydrogel with high tensile strength (~5.14 MPa), high stretchability (~1000%), high toughness (~20.36 MJ/m3) and excellent flexibility (~0.53 MPa). In addition, programmable shape deformation hydrogel is achieved by selective coating of Fe3+ on surface, the hydrogel strips can be deformed into arbitrary shapes such as the letter “o”, “d”, “s”, and “w”. More impressively, reversible shape recovery of hydrogel has been achieved via two methods: the elimination of coated Fe3+ with the reaction of NaOH and the dehydration of the glycerin. Taking advantage of this property, we simulate the closure and opening of hydrogel flower by soaking it into water and NaOH/glycerin alternately. Moreover, the soft robotic gripper has been fabricated based on the mechanically strong and solvent-triggered hydrogel, capable of grabbing about 1.56 times its own weight, which indicating the potential application as load-carrying soft robots.

Wafer-Scale Patterning of Protein Templates for Hydrogel Fabrication.

Human-induced pluripotent stem cell-derived cardiomyocytes are a potentially unlimited cell source and promising patient-specific in vitro model of cardiac diseases. Yet, these cells are limited by immaturity and population heterogeneity. Current in vitro studies aiming at better understanding of the mechanical and chemical cues in the microenvironment that drive cellular maturation involve deformable materials and precise manipulation of the microenvironment with, for example, micropatterns. Such microenvironment manipulation most often involves microfabrication protocols which are time-consuming, require cleanroom facilities and photolithography expertise. Here, we present a method to increase the scale of the fabrication pipeline, thereby enabling large-batch generation of shelf-stable microenvironment protein templates on glass chips. This decreases fabrication time and allows for more flexibility in the subsequent steps, for example, in tuning the material properties and the selection of extracellular matrix or cell proteins. Further, the fabrication of deformable hydrogels has been optimized for compatibility with these templates, in addition to the templates being able to be used to acquire protein patterns directly on the glass chips. With our approach, we have successfully controlled the shapes of cardiomyocytes seeded on Matrigel-patterned hydrogels.

Rapid digital light 3D printing enabled by a soft and deformable hydrogel separation interface

The low productivity of typical 3D printing is a major hurdle for its utilization in large-scale manufacturing. Innovative techniques have been developed to break the limitation of printing speed, however, sophisticated facilities or costly consumables are required, which still substantially restricts the economic efficiency. Here we report that a common stereolithographic 3D printing facility can achieve a very high printing speed (400 mm/h) using a green and inexpensive hydrogel as a separation interface against the cured part. In sharp contrast to other techniques, the unique separation mechanism relies on the large recoverable deformation along the thickness direction of the hydrogel interface during the layer-wise printing. The hydrogel needs to be extraordinarily soft and unusually thick to remarkably reduce the adhesion force which is a key factor for achieving rapid 3D printing. This technique shows excellent printing stability even for fabricating large continuous solid structures, which is extremely challenging for other rapid 3D printing techniques. The printing process is highly robust for fabricating diversified materials with various functions. With the advantages mentioned above, the presented technique is believed to make a large impact on large-scale manufacturing.

Fracture, fatigue, and friction of polymers in which entanglements greatly outnumber cross-links.

In gels and elastomers, the role of entanglements on deformation has been studied, but their effects on fracture, fatigue, and friction are less well understood. In this study, we synthesized polymers in which entanglements greatly outnumber cross-links. The dense entanglements enable transmission of tension in a polymer chain along its length and to many other chains. The sparse cross-links prevent the polymer chains from disentangling. These polymers have high toughness, strength, and fatigue resistance. After submersion in water, the polymers swell to equilibrium, and the resulting hydrogels have low hysteresis, low friction, and high wear resistance.

Toughening hydrogels through force-triggered chemical reactions that lengthen polymer strands.

The utility and lifetime of materials made from polymer networks, including hydrogels, depend on their capacity to stretch and resist tearing. In gels and elastomers, those mechanical properties are often limited by the covalent chemical structure of the polymer strands between cross-links, which is typically fixed during the material synthesis. We report polymer networks in which the constituent strands lengthen through force-coupled reactions that are triggered as the strands reach their nominal breaking point. In comparison with networks made from analogous control strands, reactive strand extensions of up to 40% lead to hydrogels that stretch 40 to 50% further and exhibit tear energies that are twice as large. The enhancements are synergistic with those provided by double-network architectures and complement other existing toughening strategies.

Deformable microparticles for shuttling nanoparticles to the vascular wall.

Vascular-targeted drug carriers must localize to the wall (i.e., marginate) and adhere to a diseased endothelium to achieve clinical utility. The particle size has been reported as a critical physical property prescribing particle margination in vitro and in vivo blood flows. Different transport process steps yield conflicting requirements-microparticles are optimal for margination, but nanoparticles are better for intracellular or tissue delivery. Here, we evaluate deformable hydrogel microparticles as carriers for transporting nanoparticles to a diseased vascular wall. Depending on microparticle modulus, nanoparticle-loaded poly(ethylene glycol)-based hydrogel microparticles delivered significantly more 50-nm nanoparticles to the vessel wall than freely injected nanoparticles alone, resulting in >3000% delivery increase. This work demonstrates the benefit of optimizing microparticles' efficient margination to enhance nanocarriers' transport to the vascular wall.

Synthetic platelet microgels containing fibrin knob B mimetic motifs enhance clotting responses.

Native platelets are crucial players in wound healing. Key to their role is the ability of their surface receptor GPIIb/IIIa to bind fibrin at injury sites, thereby promoting clotting. When platelet activity is impaired as a result of traumatic injury or certain diseases, uncontrolled bleeding can result. To aid clotting and tissue repair in cases of poor platelet activity, our lab has previously developed synthetic platelet-like particles capable of promoting clotting and improving wound healing responses. These are constructed by functionalizing highly deformable hydrogel microparticles (microgels) with fibrin-binding ligands including a fibrin-specific whole antibody or a single-domain variable fragment. To improve the translational potential of these clotting materials, we explored the use of fibrin-binding peptides as cost-effective, robust, high-specificity alternatives to antibodies. Herein, we present the development and characterization of soft microgels decorated with the peptide AHRPYAAK that mimics fibrin knob 'B' and targets fibrin hole 'b'. These "Fibrin-Affine Microgels with Clotting Yield" (FAMCY) were found to significantly increase clot density in vitro and decrease bleeding in a rodent trauma model in vivo. These results indicate that FAMCYs are capable of recapitulating the platelet-mimetic properties of previous designs while utilizing a less costly, more translational design.

In Situ Surface-enhanced Raman Scattering Spectroscopic Study of a Redox-active Deformable Hydrogel on a Roughened Au Electrode Surface

A highly deformable hydrogel, viologen pendant poly-L-lysine-based glutaraldehyde cross-linked hydrogel (PLLV-GA-gel), was characterized using surface-enhanced Raman scattering (SERS) signals under...

Mechanically Strong, Tough, and Shape Deformable Poly(acrylamide-co-vinylimidazole) Hydrogels Based on Cu2+ Complexation.

Shape deformable hydrogels have drawn great attention due to their wide applications as soft actuators. Here we report a novel kind of mechanically strong, tough, and shape deformable poly(acrylamide-co-vinylimidazole) [poly(AAm-co-VI)] hydrogel prepared by photoinitiated copolymerization and the followed immersing in a Cu2+ aqueous solution. Strong Cu2+ complexation with imidazole groups dramatically enhances the mechanical properties of the hydrogels, whose tensile strength, elastic modulus, toughness, and fracture energy reach up to 7.7 ± 0.76 MPa, 15.4 ± 1.2 MPa, 23.2 ± 2.5 MJ m-3, and 22.1 ± 2.3 kJ m-2, respectively. More impressively, shape deformation (bending) can be easily achieved by coating Cu2+ solution on one side of hydrogel strips. Furthermore, precise control of the shape deformation from 1D to 2D and 2D to 3D can be achieved by adjusting Cu2+ concentration, coating time, region, and one or two side(s) of hydrogel samples. The Cu2+ complexation provides a simple way to simultaneously improve the mechanical properties of hydrogels and enable them with shape deformability. The mechanically strong, tough, and shape deformable hydrogels might be a promising candidate for soft actuators.

Molecularly imprinted polymers hydrogel for the rapid risk-category-specific screening of food using SPE followed by fluorescence spectrometric detection

In fluorescence measurement, one pressing concern today is to construct sensors that can withstand various disturbances for highly selective and sensitive detection of trace analytes in complicated samples. Molecularly imprinted polymers (MIPs) with tailored binding sites are preferred to be recognition elements in sensors for effective target detection. Here, MIPs combined with solid-phase extraction (SPE), followed by direct fluorescence detection on the same extraction medium, was proposed for rapid onsite selective screening for risk categories in food safety without sample pretreatment. A novel surface solid-phase fluorescence substrate with special adsorption property for rhodamine B (RhB) or sulfamethoxazole (SMX) was synthesized by wrapping the MIPs in the deformable hydrogel prepared by polyvinyl alcohol (PVA). Parameters that affected the extraction capacity of the analytes were explored. MIPs-PVA hydrogel showed a good selectivity (imprinting factor α = 2.95 with RhB-MIPs-PVA hydrogel), reproducibility (RSD ≤ 16.5% with 5 ppm RhB) and sensitivity (0.1 ppm to RhB) with a short analysis time of less than 5 min including sampling. The proposed method is very promising as a rapid, onsite screening protocol for food safety.