Elastic Hydrogel Research Articles

Ultra stretchable, tough, elastic and transparent hydrogel skins integrated with intelligent sensing functions enabled by machine learning algorithms

Hydrogel-based ionic skins are ionic conductive artificial skin-like materials that are promising for a broad range of applications such as wearable sensory devices, soft robotics and machines, and bioelectronics. However, fabricating hydrogel skins with satisfying mechanical performance and intelligent sensing functions is still a significant challenge. Herein, we have developed an ionic conductive nanocomposite hydrogel with ultra stretchability and self-evolving sensing functions. By leveraging the dynamic feature of synergetic interfacial ionic interactions, a trace amount of carbon nanotubes endows the hydrogel networks with excellent mechanical performances (i.e., tensile strength, stretchability and toughness up to 1.09 MPa, 4075 % and 12.8 MJ/m3, respectively). Additionally, the hydrogel is soft, elastic, transparent and self-healing. The rational combination of the mechanical and electrical properties renders the as-prepared hydrogel with excellent sensing performances and cycling stability, and therefore enables it to perform as a sensory unit of a complete platform for the recognition of some complicated human behaviors, outperforming the previously reported hydrogels due to its intelligent sensing functions. Specifically, with the integration of machine learning module, the hydrogel-based platform exhibits great recognition accuracies to human handwriting motions from single letters to words, phrases, and short sentences after proper training. The combination of superior mechanical performances and self-evolving sensing functions within this hydrogel-based ionic skin unlocks its potential as the intelligent human-device interface, which promotes the application of artificial intelligence in customized electronic devices.

Synthesis and Rheological Characterization of a Novel Salecan Hydrogel.

Salecan (Sal) is a novel microbial polysaccharide. In the present research, thermal treatment was performed to fabricate Sal hydrogel. The effect of Sal concentration on water holding capacity, swelling properties, texture properties, and microstructure of the hydrogels was discussed. It was found that the equilibrium degree of swelling (EDS) of Sal hydrogels was above 1500%, inferred Sal was a highly hydrophilic polysaccharide. As Sal concentration increased from 3.5 to 8.0 wt%, the hardness increased from 0.88 to 2.07 N and the water hold capability (WHC) increased from 91.3% to 98.2%. Furthermore, the internal network structure of Sal hydrogel also became denser and more uniform. Rheological studies suggested that elastic hydrogel formed under the gelation process. All these results demonstrated that Sal hydrogel prepared by thermal treatment had good gelling properties, which opened up a new safe way for the preparation of Sal hydrogel and broadened the application range of Sal.

Second-order elasticity of polymeric hydrogels with chemically coupled effects

In this paper, a second-order elastic model is formulated for polymeric hydrogels subject to chemo-mechanical coupled field. A third-order phenomenological free energy density is theoretically formulated based on the classical Flory-Huggins solution theory, and a fully coupled chemo-mechanical expression is obtained for the Lamé constants and second-order elastic constants, where the chemical influences are considered.The chemically induced swelling is analytically investigated for characterization of the chemically coupled elastic constants, where the relationship is revealed among the elastic constants, the swelling ratio, and the chemical potential. The effects of Flory parameter and degree of cross-linking are then theoretically analyzed on the elastic constants. Application of the present model to simple tension reveals the classical relation among the Lamé constants, Young's modulus and Poisson's ratio, where all the constants are dependent on the chemical potential. In addition, a stiffening effect is observed for the effect of second-order elastic parameters, where good agreement is presented with experimental data (Urayama et al., 2006).This model presents a theoretical platform to simulate the responsive behavior of polymeric hydrogels subject to chemo-mechanical coupled stimuli. The resultant elastic constants couple the chemical and mechanical effects, and may provide a comprehensive guide to structure analysis and design of soft materials.

Mechanical checkpoint regulates monocyte differentiation in fibrotic niches.

Myelofibrosis is a progressive bone marrow malignancy associated with monocytosis, and is believed to promote the pathological remodelling of the extracellular matrix. Here we show that the mechanical properties of myelofibrosis, namely the liquid-to-solid properties (viscoelasticity) of the bone marrow, contribute to aberrant differentiation of monocytes. Human monocytes cultured in stiff, elastic hydrogels show proinflammatory polarization and differentiation towards dendritic cells, as opposed to those cultured in a viscoelastic matrix. This mechanically induced cell differentiation is blocked by inhibiting a myeloid-specific isoform of phosphoinositide 3-kinase, PI3K-γ. We further show that murine bone marrow with myelofibrosis has a significantly increased stiffness and unveil a positive correlation between myelofibrosis grading and viscoelasticity. Treatment with a PI3K-γ inhibitor in vivo reduced frequencies of monocyte and dendritic cell populations in murine bone marrow with myelofibrosis. Moreover, transcriptional changes driven by viscoelasticity are consistent with transcriptional profiles of myeloid cells in other human fibrotic diseases. These results demonstrate that a fibrotic bone marrow niche can physically promote a proinflammatory microenvironment.

Additive Manufacturing of Viscoelastic Polyacrylamide Substrates for Mechanosensing Studies.

Polymerized polyacrylamide (PAA) substrates are linearly elastic hydrogels that are widely used in mechanosensing studies due to their biocompatibility, wide range of functionalization capability, and tunable mechanical properties. However, such cellular response on purely elastic substrates, which do not mimic the viscoelastic living tissues, may not be physiologically relevant. Because the cellular response on 2D viscoelastic PAA substrates remains largely unknown, we used stereolithography (SLA)-based additive manufacturing technique to create viscoelastic PAA substrates with tunable mechanical properties that allow us to identify physiologically relevant cellular behaviors. Three PAA substrates of different complex moduli were fabricated by SLA. By embedding fluorescent markers during the additive manufacturing of the substrates, we show a homogeneous and uniform composition throughout, which conventional manufacturing techniques cannot produce. Rheological investigation of the additively manufactured PAA substrates shows a viscoelastic behavior with a 5–10% loss moduli compared to their elastic moduli, mimicking the living tissues. To understand the cell mechanosensing on the dissipative PAA substrates, single live cells were seeded on PAA substrates to establish the basic relationships between cell traction, cytoskeletal prestress, and cell spreading. With the increasing substrate moduli, we observed a concomitant increase in cellular traction and prestress, but not cell spreading, suggesting that cell spreading can be decoupled from traction and intracellular prestress in physiologically relevant environments. Together, additively manufactured PAA substrates fill the void of lacking real tissue like viscoelastic materials that can be used in a variety of mechanosensing studies with superior reproducibility.

UV-curable hybrid hydrogels of carbon quantum dots: synthesis, characterizations and investigation of properties and rheological behavior

ABSTRACT In this study, we are going to produce UV-curable hydrogel hybrids with carbon quantum dots. For this purpose, after synthesizing CQDs, they were reacted with acrylic acid to establish covalent bonds and create a C = C bond on the surface of CQDs. Then acrylamide hydrogel was synthesized. In the next step, 1, 3 and 5% UV-curable hydrogel hybrids were prepared. The experimental results displayed that increasing the amount of CQDs in the hydrogel increased photoluminescence intensity and water adsorption while boosting the hydrogel’s thermal stability. Besides, increasing the CQDs amount reduces the hydrogel elasticity.

Emergence of Elastic Properties in a Minimalist Resilin-Derived Heptapeptide upon Bromination.

Bromination is herein exploited to promote the emergence of elastic behavior in a short peptide-SDSYGAP-derived from resilin, a rubber-like protein exerting its role in the jumping and flight systems of insects. Elastic and resilient hydrogels are obtained, which also show self-healing behavior, thanks to the promoted non-covalent interactions that limit deformations and contribute to the structural recovery of the peptide-based hydrogel. In particular, halogen bonds may stabilize the β-sheet organization working as non-covalent cross-links between nearby peptide strands. Importantly, the unmodified peptide (i.e., wild type) does not show such properties. Thus, SDSY(3,5-Br)GAP is a novel minimalist peptide elastomer.

Strong and Elastic Hydrogels from Dual-Crosslinked Composites Composed of Glycol Chitosan and Amino-Functionalized Bioactive Glass Nanoparticles.

Mesoporous bioactive glass (BG) nanoparticles (NPs) with a high specific surface area were prepared. The surfaces of BG NPs were further modified using an amino-containing compound or synthesized precursors to produce three kinds of amino-functionalized bioactive glass (ABG) NPs via devised synthetic routes. The achieved ABG NPs possessed various spacer lengths with free amino groups anchored at the end of the spacer. These ABG NPs were then combined with glycol chitosan (GCH) to construct single- or dual-crosslinked ABG/GCH composite hydrogels using genipin (GN) alone as a single crosslinker or a combination of GN and poly(ethylene glycol) diglycidyl ether (PEGDE) as dual crosslinkers. The spacer length of ABG NPs was found to impose significant effects on the strength and elasticity of GN-crosslinked ABG/GCH hydrogels. After being dually crosslinked with GN and PEGDE, the elastic modulus of some dual-crosslinked ABG/GCH hydrogels reached around 6.9 kPa or higher with their yielding strains larger than 60%, indicative of their strong and elastic features. The optimally achieved ABG/GCH hydrogels were injectable with tunable gelation time, and also able to support the growth of seeded MC3T3-E1 cells and specific matrix deposition. These results suggest that the dual-crosslinked ABG/GCH hydrogels have the potential for some applications in tissue engineering.

A comparative study of niosomal and elastic niosomal carbomer hydrogel for transcutaneous vaccine delivery

Transcutaneous immunization is becoming an attractive non-invasive vaccination strategy, though it is still challenging. This study evaluates the potential of transcutaneous delivery of antigens in mice through niosomal and elastic niosomal carbomer hydrogels. Ovalbumin was encapsulated into niosomes prepared by Span 80/cholesterol/stearylamine through reverse-phase evaporation. Ethanol was added into niosomal mixtures for elastic niosomes formation, then embedded in carbopol 934 hydrogel. Encapsulation efficiency and other physiochemical properties of the prepared niosomal vesicles such as particle size, stability, in vitro release and cytotoxicity were determined. In vivo immunizations of niosomal and elastic niosomal gel were carried out in mice. The optimal niosomal formulation loads 48.6 ± 5.2% ovalbumin with a vesicle size below 300 nm. A simple BCA method was used to determine the encapsulation efficiency of niosome. The cumulative permeation of proteins of niosomal gel was 15~20%. Both gels were stable at room temperature; however, elastic niosomal gel deteriorated at 60 ℃. Compared to free antigen, the topical administration of niosomal or elastic niosomal gel to mice displayed significant IgG titers. From the findings, compared to elastic niosomal gel, the niosomal hydrogel platform exhibited enhanced antigen delivery. Therefore, niosomal hydrogel may be considered a promising transcutaneous antigen delivery carrier.

Aqueous condition-tolerated high internal phase oil-in-water Pickering emulsion as building block for engineering 3D functional materials

Conventional high internal phase oil-in-water Pickering emulsions (HIPPEs) have limited applicability as building blocks for fabricating functional materials due to the aqueous condition-dependent stability. The hydrocarbon chain-grafted cellulose nanocrystals (H-CNCs) act as effective stabilizers to stabilize HIPPE. With the attractive hydrophobic forces between the hydrocarbon chains grafted on H-CNC surfaces, the emulsion droplets of H-CNC-stabilized HIPPE exhibit severe flocculation and such HIPPE at stabilizer contents as low as 0.06 w/v% (based on emulsion volume) display promising rheologies such as shear-thinning behaviors, viscoelasticity, rapid thixotropic recovery, and satisfactory stability against inter-droplet repulsions under a wide range of different aqueous conditions (pH scale: 3 to 12, ionic strength: 0 to 1 M NaCl and stabilizer content: ≥ 0.06 w/v%) and oil volume fractions (66% − 83%). By varying aqueous conditions/compositions and oil volume fractions while maintaining robust stability and promising rheological behaviors, the HIPPEs show the broad applicability as building blocks to print or build functional three-dimensional materials such as ultra-lightweight porous scaffolds with tunable pore sizes, stimuli-responsive hydrogels for controlled release of internal phase, elastic hydrogel sensors susceptible to weak forces and porous material with excellent thermal insulation performance, demonstrating the versatility of such H-CNC-stabilized HIPPEs in engineering state-of-the-art functional materials.

Enzymatic co-crosslinking of star-shaped poly(ethylene glycol) tyramine and hyaluronic acid tyramine conjugates provides elastic biocompatible and biodegradable hydrogels.

A combination of the viscoelastic properties of hyaluronic acid (HA) and the elastic properties of star shaped 8-arm poly(ethylene glycol) (8-arm PEG) was used to design in-situ forming hydrogels. Hydrogels were prepared by the enzymatic crosslinking of a partially tyramine modified 8-arm PEG and a tyramine conjugated HA using horseradish peroxidase in the presence of hydrogen peroxide. Hydrogels of the homopolymer conjugates and mixtures thereof were rapidly formed within seconds under physiological conditions at low polymer and enzyme concentrations. Elastic hydrogels with high gel content (≥95%) and high storage moduli (up to 22.4 kPa) were obtained. An in vitro study in the presence of hyaluronidase (100 U/mL) revealed that with increasing PEG content the degradation time of the hybrid hydrogels increased up to several weeks, whereas hydrogels composed of only hyaluronic acid degraded within 2 weeks. Human mesenchymal stem cells (hMSCs) incorporated in the hybrid hydrogels remained viable as shown by a PrestoBlue and a live-dead assay, confirming the biocompatibility of the constructs. The production of an extracellular matrix by re-differentiation of encapsulated human chondrocytes was followed over a period of 28 days. Gene expression indicated that these highly elastic hydrogels induced an enhanced production of collagen type II. At low PEG-TA/HA-TA ratios a higher expression of SOX 9 and ACAN was observed. These results indicate that by modulating the ratio of PEG/HA, injectable hydrogels can be prepared applicable as scaffolds for tissue regeneration applications.

Design of asymmetric-adhesion lignin-reinforced hydrogels based on disulfide bond crosslinking for strain sensing application

Soft and elastic polymer hydrogel materials are booming in the fields of wearable biomimetic skin, sensors, robotics, and bioelectrodes. Currently, many researchers are exploring new chemistries for the preparation of hydrogels to improve their performance. In the present study, we design and develop a strategy to prepare lignin reinforced hydrogels based on disulfide bond crosslinking mechanisms, and resultant hydrogels exhibit excellent stretchability, with tensile strain of up to 1085.4%, and high adhesion (with the highest T-peel strength of up to 432.2 N/m to pigskin). The underlying mechanism is based on the disulfide bonds that act as crosslinkers in the as-prepared hydrogel, and they can be easily cleaved and re-formed under mild conditions. Thanks to the presence of lignin, the as-obtained hydrogels also have excellent UV shielding effect. When assembled into a strain sensor, they can output stable and sensitive sensing signals, with gauge factor (GF) of 2.72 (strain: 0–72.8%). Furthermore, a simple and effective strategy to construct asymmetric adhesive hydrogels was adopted, which is based on directional soaking of the top portion of the hydrogel in a high-concentrated calcium chloride solution. The asymmetric hydrogel strain sensor transmits accurate and stable signals without the interference of various contaminants.

Non-ionic polar small molecules induced transition from elastic hydrogel via viscoelastic wormlike micelles to spherical micelles in zwitterionic surfactant systems

Supramolecular assembly determines the formation and transformation of soft materials. So far, the construction and transformation of conventional (<C20) zwitterionic surfactant elastic hydrogel have been a challenging and vital issue. In this work, a C18-tailed zwitterionic surfactant supramolecular hydrogel is constructed with N-octadecyl-N,N-dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate (OHSB) and sodium salicylate (NaSal). The N,N,2,2-tetramethyl-1, 3-propanediamine (TPA1), as the non-ionic polar small molecules, were chosen to control the microstructure and macro-viscoelasticity of zwitterionic surfactant supramolecular hydrogel. With the addition of TPA1, the rheological properties and microstructural images of the OHSB/NaSal system show that the microstructure has changed from elastic hydrogels via viscoelastic wormlike micelles (WLMs) to spherical micelles. With the N,N,N’,N’-tetramethyl-1,3-propanediamine (TPA2), the isomer of TPA1, is added into OHSB/NaSal system in the same concentration, the difference in rheology and microstructure indirectly indicates the influence of hydrogen bonding on self-assembly. By systematically varying components, insight into the intermolecular interaction between OHSB, NaSal, and TPA1 and its effect on the microstructure during aggregation and transition are gained by the complementary use of 1H NMR, rheological property, cryo-SEM, cryo-TEM, and DLS. We expect it to be a good model for conventional zwitterionic surfactant supramolecular hydrogel and a new method for controlling the internal nanostructure of micelles, which is helpful to understand the construction and finely tune of conventional zwitterionic surfactant supramolecular hydrogel and widen their applications.

Highly flexible interconnected Li+ ion-sieve porous hydrogels with self-regulating nanonetwork structure for marine lithium recovery

Li+ ion-sieve (LIS) films, foams, or granules have been fabricated to immobilize LIS to overcome powder loss for Li extraction from seawater. However, the practical application is still restricted by their low swelling ability and poor flexibility to withstand harsh marine environment for a long time. Here, a highly elastic interconnected porous LIS nanocomposite hydrogel with tunable pore structure and flexibility, as well as good swelling property, is prepared by using LIS (viz. λ-MnO2) as a pore self-modifier during the in-situ fabrication of polypyrrole (PPy) and polyvinyl alcohol (PVA) interpenetrating hydrogel (denoted as λ-MnO2@IG). In addition to physical confinement interactions, the strong coordination/chelation and electrostatic interactions between λ-MnO2 nanoparticles and polymer chains enable well-dispersed λ-MnO2 nanoparticles to be confined in a rich network structure. Even at a marine environment (pH 8.3), the λ-MnO2@IG hydrogel exhibits superior Li+ adsorption performance (20.6 mg g−1 HMO), outperforming most adsorbents containing LIS. Specially, the porous hydrogel is easily recyclable and exhibits super-stable cyclic Li extraction performance, which are directly attributable to the further-improved pore structure in continuous regeneration process. This study provides a self-regulating strategy to design LIS porous hydrogels with controllable porosity, high flexibility, good swelling ability, and excellent cycle stability to address the growing Li+ demanding challenges.

Gelatin-Based Colloidal Versus Monolithic Gels to Regulate Macrophage-Mediated Inflammatory Response.

Unlike conventional monolithic hydrogels with covalent cross-linkage that are typically elastic, colloidal gels assembled by reversibly assembled particles as building blocks have shown fascinating viscoelastic properties. They follow a gel-sol transition upon yielding and recover to the initial state upon the release of the shear force (so-called shear-thinning and self-healing behavior); this makes them an ideal candidate as injectable and moldable biomaterials for tissue regeneration. The immune response provoked by the implantation of the colloidal gels with special viscoelastic and structural features is critical for the successful integration of the implants with the host tissues, which, however, remains little explored. Since macrophages are known as the primary immune cells in determining the inflammatory response against the implants, we herein investigated in vitro macrophage polarization and in vivo inflammatory response induced by gelatin-based colloidal gels as compared to monolithic gels. Specifically, self-healing colloidal gels composed of pure gelatin nanoparticles, or methacrylate gelatin (GelMA) nanoparticles to allow secondary covalent cross-linkage were compared with GelMA bulk hydrogels. We demonstrated that hydrogel's elasticity plays a more dominant role rather than the structural feature in determining in vitro macrophage polarization evidenced by the stiffer gels inducing pro-inflammation M2 macrophage phenotype as compared to soft gels. However, subcutaneous implantation revealed a significantly alleviated immune response characterized by less fibrous capsule formation for the colloidal gels as compared to bulk gels of similar matrix elasticity. We speculated this can be related to the improved permeability of the colloidal gels for cell penetration, thereby leading to less fibrosis. In general, this study provided in-depth insight into the biophysical regulator of hydrogel materials on macrophage behavior and related inflammatory response, which can further direct future implant design and predict biomaterial-host interactions for immunotherapy and regenerative medicine. Impact statement Macrophages response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Nowadays, the viscoelastic properties of colloidal versus monolithic hydrogels on macrophage phenotype in vitro and the host inflammatory response are not known. Our study found that colloidal hydrogels composed of nanoparticles of gelatin and methacrylate gelatin (GelMA) led to more anti-inflammatory polarization especially on soft colloidal gel (5.9 KPa) compared to bulk GelMA hydrogels. It suggested that macrophage response can be mechanically regulated by the viscoelastic signals of the hydrogels, which could be a promising strategy for the future design and application of novel biomaterials.

Sodium Polyacrylate Hydrogel Electrolyte Hybridized with Layered Double Hydroxide for Solid-State NiCo/Zinc Battery

Zinc-based batteries have attracted attention for their safety in aqueous electrolytes with low cost, environmental friendliness, and high capacity. In this study, layered double hydroxide, a solid-state OH− ion conductor, was hybridized with sodium polyacrylate hydrogel to construct a strong elastic hydrogel electrolyte (PANa-LDH) with high OH− ion conductivity. PANa-LDH, KOH was introduced by dipping into 6.0 M KOH solution, showed a significantly high ionic conductivity of 0.213 S cm−1 at 30 °C. A solid-state battery was fabricated using nickel-cobalt hydroxide cathode, PANa-LDH electrolyte, and zinc anode. The high specific capacity of 287 mAh g−1 was obtained at 0.1 A g−1 with high energy and power densities of 212 Wh kg−1 and 73 kW kg−1 (based on the cathode weight), respectively.

Ultra-stretchable and anti-freezing conductive organohydrogel reinforced with ionic clusters for wearable strain sensors

Ionic conductive hydrogels have attracted extensive attention as a substitute for traditional rigid metal conductors, especially in wearable electronic devices. However, to prolong the service life of ionic conductive hydrogel-based devices, the development of highly elastic ionic conductive hydrogels that can remain good performance under extreme environmental conditions (below 0 °C or dry) is still facing great challenges. Herein, a novel double-network (DN) organohydrogel with high tensile strength (~0.9 MPa), elongation at break (~1097%), compressive strength (~6.96 MPa), toughness (~4.75 MJ m−3), transparency (~97%), anti-freezing and ionic conductivity (1.07 mS cm−1) is prepared by photoinitiation polymerization, complexation of transition metal ions, and solvent exchange method using polyacrylamide (PAM) and sodium carboxymethyl cellulose (CMCNa) in dimethyl sulfoxide-water binary solvent system. It is noteworthy that the DN gel design is more compact, and zinc carboxylate complexes composed of CMCNa and Zn2+ form nanoscale metal ionic clusters through coulomb force interaction in the binary solvent environment, which proves the synergistic effect on mechanical properties and conductivity. Moreover, the prepared organohydrogels used as strain sensors have obvious recovery effect, flexibility, high sensitivity (GF=4.38) and stable electrical properties (0.6 mS cm−1 at 30 °C) under the temperature range (−20 to 60 °C). Combined with the above advantages, this conductive organohydrogel promotes the application prospect in different fields, such as soft robots, human-machine interaction, artificial sensors, ionic skin, and optical electronics devices, energy-storage devices, and so on.

Biomechanical interactions of Schistosoma mansoni eggs with vascular endothelial cells facilitate egg extravasation.

The eggs of the parasitic blood fluke, Schistosoma, are the main drivers of the chronic pathologies associated with schistosomiasis, a disease of poverty afflicting approximately 220 million people worldwide. Eggs laid by Schistosoma mansoni in the bloodstream of the host are encapsulated by vascular endothelial cells (VECs), the first step in the migration of the egg from the blood stream into the lumen of the gut and eventual exit from the body. The biomechanics associated with encapsulation and extravasation of the egg are poorly understood. We demonstrate that S. mansoni eggs induce VECs to form two types of membrane extensions during encapsulation; filopodia that probe eggshell surfaces and intercellular nanotubes that presumably facilitate VEC communication. Encapsulation efficiency, the number of filopodia and intercellular nanotubes, and the length of these structures depend on the egg’s vitality and, to a lesser degree, its maturation state. During encapsulation, live eggs induce VEC contractility and membranous structures formation in a Rho/ROCK pathway-dependent manner. Using elastic hydrogels embedded with fluorescent microbeads as substrates to culture VECs, live eggs induce VECs to exert significantly greater contractile forces during encapsulation than dead eggs, which leads to 3D deformations on both the VEC monolayer and the flexible substrate underneath. These significant mechanical deformations cause the VEC monolayer tension to fluctuate with the eventual rupture of VEC junctions, thus facilitating egg transit out of the blood vessel. Overall, our data on the mechanical interplay between host VECs and the schistosome egg improve our understanding of how this parasite manipulates its immediate environment to maintain disease transmission.

In situ crosslinking temperature-responsive hydrogels with improved delivery, swelling, and elasticity for endovascular embolization.

Endovascular embolization of cerebral aneurysms is a common approach for reducing the risk of often-fatal hemorrhage. However, currently available materials used to occlude these aneurysms provide incomplete filling (coils) or require a complicated, time-consuming delivery procedure (solvent-exchange precipitating polymers). The objective of this work was to develop an easily deliverable in situ forming hydrogel that can occlude the entire volume of an aneurysm. The hydrogel is formed by mixing a solution of a temperature-responsive polymer containing pendent thiol groups (poly(NIPAAm-co-cysteamine) or poly(NIPAAm-co-cysteamine-co-JAAm)) with a solution of poly(ethylene glycol) diacrylate (PEGDA). Incorporation of hydrophilic grafts of polyetheramine acrylamide (JAAm) in the temperature-responsive polymer caused weaker physical crosslinking, facilitated faster and more complete chemical crosslinking, and increased gel swelling. One formulation (30 wt % PNCJ20 + PEGDA) could be delivered for over 220 s after mixing, formed a strong and elastic hydrogel (G' > 6000 Pa) within 30 min and once set, maintained its shape and volume in a model aneurysm under flow. This gel represents a promising candidate water-based material utilizing both physical and chemical crosslinking that warrants further investigation as an embolic agent for saccular aneurysms.

Nonswelling and Hydrolytically Stable Hydrogels Uncover Cellular Mechanosensing in 3D.

While matrix stiffness regulates cell behavior on 2D substrates, recent studies using synthetic hydrogels have suggested that in 3D environments, cell behavior is primarily impacted by matrix degradability, independent of stiffness. However, these studies did not consider the potential impact of other confounding matrix parameters that typically covary with changes in stiffness, particularly, hydrogel swelling and hydrolytic stability, which may explain the previously observed distinctions in cell response in 2D versus 3D settings. To investigate how cells sense matrix stiffness in 3D environments, a nonswelling, hydrolytically stable, linearly elastic synthetic hydrogel model is developed in which matrix stiffness and degradability can be tuned independently. It is found that matrix degradability regulates cell spreading kinetics, while matrix stiffness dictates the final spread area once cells achieve equilibrium spreading. Importantly, the differentiation of human mesenchymal stromal cells toward adipocytes or osteoblasts is regulated by the spread state of progenitor cells upon initiating differentiation. These studies uncover matrix stiffness as a major regulator of cell function not just in 2D, but also in 3D environments, and identify matrix degradability as a critical microenvironmental feature in 3D that in conjunction with matrix stiffness dictates cell spreading, cytoskeletal state, and stem cell differentiation outcomes.