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Tannin-bearing hydrogel adhesives with enhanced mechanical and adhesion strength in response to protein leakage.

Anastomotic leaks are among the most severe side effects following abdominal surgeries. Conventional surgical sealants and emerging hydrogel adhesives often lose mechanical and adhesion strength when exposed to leaked digestive enzymes. Here, we report a tannin-encapsulating tough hydrogel adhesive that exhibits enhanced mechanical and adhesive properties upon the encounter of leaked proteins. The hydrogel is composed of a gelatin-acrylate crosslinked network with encapsulated tannin and can adhere to a wet surface via amine-carboxyl chemistry. In the context of anastomotic leaks, tannin within the hydrogel can form a complex with proteins including the digestive enzymes, leading to increased gel stiffness and storage modulus. The enhanced mechanical strength confers improved adhesive properties on the hydrogel adhesive. Additionally, the tannin-bearing hydrogel adhesive shows excellent antibacterial properties. This adaptive and antibacterial hydrogel adhesive provides a promising sealant for gastrointestinal surgery and other applications.

Tannins

The reactivity of alpha-chymotrypsin immobilized on radiation-grafted hydrogel surfaces.

The enzymatic activity of alpha-chymotrypsin (CT), immobilized on hydrogel-coated polymer film supports, has been investigated. The support was prepared by radiation-graft copolymerization of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAAc) on silicone rubber films. The enzyme was covalently coupled to the carboxylic group of MAAc via the N-hydroxysuccinimide (NHS) ester active intermediate. Increasing MAAc contents of the hydrogel resulted in increased attachment of CT. The integrity of the CT active site after attachment was assessed by an active site titration with diisopropyl fluorophosphate (DFP). As the MAAc content of the hydrogel was increased, an increasing fraction of the attached CT retained its activity to DFP. A greater fraction of CT was active towards DFP when adsorbed than when coupled. The rates of hydrolysis of some synthetic model substrates by the immobilized CT were also measured. The negative charge on the hydrogel had a large effect on the rates of these hydrolyses. The pH optimum for the hydrolysis of N-acetyl-L-tyrosine ethyl ester (ATEE) by immobilized CT was higher than that of free CT. Increasing MAAc content of the hydrogel resulted in larger shifts in the pH optimum. The maximum rates of ATEE hydroylsis per mg CT declined sharply with increasing MAAc content of the hydrogel. This is probably related to the increasing repulsive force between the ATEE (negatively charged above congruent to pH 9.5) and the hydrogel with increasing MAAc content. The activity of immobilized CT to ATEE is small compared to that of free CT, partly due to this charge effect. Conversely, the rate of hydrolysis of BAEE, a positively charged substrate, by immobilized CT at pH 11, is almost fourfold greater than that by free CT at its pH optimum.

Adsorption

Granular Hydrogels as Brittle Yield Stress Fluids.

While granular hydrogels are increasingly used in biomedical applications, methods to capture their rheological behavior generally consider shear-thinning and self-healing properties or produce ensemble metrics (e.g., dynamic moduli) while neglecting transient yielding and unyielding processes. Combining oscillatory shear testing with Brittility (Bt) via the Kamani-Donley-Rogers (KDR) model, this work shows that granular hydrogels behave as brittle yield stress fluids. This work quantifies steady and transient rheology as a function of microgel properties and granular composition for polyethylene glycol and gelatin microgels. The KDR model with Bt captures granular hydrogel behavior for a wide range of design parameters, reducing the complex rheology to a determination of model parameters. In granular mixtures, this work observes monotonic dependencies of the elastic modulus, structural viscosity, and brittility upon granular composition, while the yield stress is lower for mixtures. Microgel size distribution and polymer fraction are the most influential parameters in monolithic granular hydrogels, while microgel size and packing density are less impactful. The model robustly captures self-healing behavior and reveals that granular hydrogel relaxation accelerates with an increased small-amplitude strain rate. This quantitative framework is an important step toward rational design of granular hydrogels for applications ranging from injection and in situ stabilization to 3D bioprinting.

brittility

Biomimetic Hydrogels with Nucleus Pulposus-like Viscoelasticity and ECM Peptides for Discogenic Differentiation of Stem Cells.

Intervertebral disc (IVD) degeneration is a leading cause of low back pain (LBP), primarily originating in the nucleus pulposus (NP). Regenerative strategies combining mesenchymal stem cells (MSCs) with biomaterials offer great potential for NP repair by replenishing cells and restoring extracellular matrix (ECM). However, key translational challenges remain, including limited stem cell differentiation, poor cell survival in the harsh degenerative niche, and insufficient biomaterial support. While matrix viscoelasticity has been shown to influence adipose-derived stem cell (ASC) discogenic differentiation, its interplay with cell-adhesive ligands for IVD regeneration remains unclear. Moreover, most current hydrogels fail to replicate the ultrafast stress relaxation properties of native non-degenerative human NP tissue. Here, we developed viscoelastic ECM peptide-functionalized hydrogels (VEPH), specifically designed to mimic healthy human NP biomechanics and promote ASC differentiation for NP regeneration. We biochemically conjugated NP ECM-derived adhesive peptides (IKVAV, hA5G26, CHAD) through maleimide-thiol click chemistry, achieving hydrogels with significantly faster stress relaxation (∼25 s) compared to conventional viscoelastic alginate hydrogels (>100 s). Our results demonstrated that VEPH supported >95% ASC viability and robust metabolic activity over 21 days in 3D culture. Notably, the IKVAV-functionalized hydrogel significantly enhanced ASC cell-matrix interactions, upregulated NP marker expression (KRT18, HIF-1α, ITGA3, and CD24), and promoted type-II collagen secretion, indicating an NP-committed cell fate. Our findings highlight the synergistic roles of matrix viscoelasticity and NP-specific biochemical cues in directing ASC discogenic differentiation and advancing novel biomaterial design for IVD regeneration.

cell-adhesive peptides

Progestin permeation through polymer membranes III: Polymerization solvent effect on progesterone permeation through hydrogel membranes.

Hydrogels prepared from poly(hydroxyethyl methacrylate) are biocompatible and highly permeable to low molecular weight solutes. Permeation rates can be varied by altering the cross-linker concentration or using copolymers; the latter are chosen to alter the hydrogel equilibrium hydration. These factors suggest that hydrogels are good candidates for controlled-release drug delivery devices. Hydrogels may be synthesized using various temperatures, initiators (nature and concentration), and solvents (nature and concentration). This study demonstrated that progesterone permeation through poly(hydroxyethyl methacrylate) films is independent of polymerization solvent (nature and concentration) for the solvents, water, ethanol, and tert-butyl alcohol. The importance of hydrogel equilibrium hydration in progesterone permeation is emphasized.

Acrylic Resins

Progestin permeation through polymer membranes II: diffusion studies on hydrogel membranes.

The potential use of hydrogels in controlled-release drug delivery systems for contraceptive steroids was investigated. The permeabilities, diffusion coefficients, and partition coefficients for progesterone were determined for hydrogels made from hydroxyethyl methacrylate containing varying amounts of ethylene glycol dimethacrylate and tetraethylene glycol dimethacrylate. In addition, copolymers of hydroxyethyl methacrylate with methoxyethyl methacrylate and methoxyethoxyethyl methacrylate were investigated. The results were interpreted in terms of the mechanisms of permeation of progesterone through the hydrogels. This study showed that progesterone permeated these membranes primarily through loose pores in the hydrogel network except at high concentrations of the cross-linker, ethylene glycol dimethacrylate, where dissolution and diffusion of the progesterone in the polymer network was the dominant mechanism.

Acrylic Resins

Reliability and repeatability study of a technique for measuring the center thickness of a hydrogel lens.

Various techniques of measuring the center thickness of hydrogel contact lenses are discussed. A new device called the Bisurfaced Hydrogel Lens Platform (BHLP) is described which in combination with the radiuscope allows for easy measurement of the center thickness of hydrogel lenses. The results of reliability and repeatability studies of this new device are reported which suggest the ability to measure the center thickness of hydrogel lenses within a range of .01 mm.

Contact Lenses, Hydrophilic

An All-in-One Photothermal Nanocomposite Hydrogel for Controlling Inducible Transgene Expression.

We have developed a remotely near-infrared (NIR)-activated, implantable fibrin hydrogel for the controlled induction of transgene expression, designed to decouple the therapeutic efficacy of rapamycin from its systemic toxicity. Rapamycin, a drug widely used in clinical practice as an immunosuppressant and antiproliferative agent, is a potent transcriptional inducer that enables tightly regulated temporal transgene expression through chemically induced dimerization. However, its utility as a dimerizer is hindered by the unintended systemic immunosuppression and off-target effects inherent to its conventional administration. To address this, we developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate rapamycin, aiming to facilitate localized delivery and enhance drug stability. Engineered cells harboring a dual heat- and dimerizer-responsive gene switch exhibited robust reporter transgene expression following nanoparticle treatment and thermal activation. Nanoencapsulation preserved rapamycin activity against thermal and hydrolytic degradation, enabling superior, long-term dimerizer function compared to the free drug. To create a remotely actuated platform, we developed photothermal hydrogels by incorporating hollow gold nanoparticles and rapamycin-loaded PLGA nanoparticles within a fibrin matrix hosting the reporter cells. In mice, NIR irradiation of subcutaneously implanted constructs achieved transgene induction levels comparable to systemic administration of rapamycin. Notably, nanoparticle-mediated delivery resulted in negligible circulating rapamycin concentrations. Furthermore, localized rapamycin release initially promoted a pro-healing M2 macrophage phenotype, followed by a late-stage transition toward an M1-dominant profile that likely facilitated the clearance of scaffold degradation products. In hydrogels incorporating cells harboring a gene switch to control human VEGF165 production, NIR irradiation triggered a robust angiogenic cascade characterized by transient erythema followed by an increase in CD31+ microvascular density. Collectively, these data demonstrate the potential of this light-triggered and rapamycin-dependent platform as a customizable and safe tool for achieving the control required to advance the next-generation of site-specific, transgenic protein therapies.

Animals

Cell-body curvature reduces stall frequency to enhance Vibrio cholerae swimming and chemotaxis through hydrogels.

The swimming motility of the bacterial pathogen Vibrio cholerae is a virulence factor that aids in breaching the mucus layer. V. cholerae has a curved cell shape, and previous work demonstrated that loss of curvature decreases infectivity. Here, we investigate the mechanism by which curvature affects single-cell motility. We compared the chemotactic performance of wild-type curved cells and straight mutants. The two exhibit similar swimming properties in liquid and viscous solutions but differ significantly in mucus-mimicking hydrogels, where curved cells demonstrate an 86% increase in chemotactic drift. Trajectory analysis indicates comparable swimming speeds, but straight mutants experience more frequent stalls, reducing total swimming time. Stalls further reduce chemotactic performance by imposing an average reorientation down the chemical gradient, regardless of cell shape. Coarse-grained molecular dynamics simulations corroborate these results across intestinal mucus hydrogel stiffnesses and identify an optimal curvature for movement through hydrogel-like meshes, close to the pathogen's median curvature. These findings highlight cell shape's role in pathogenicity and the need to study bacterial behaviors under conditions more closely mimicking the host environment.

Vibrio cholerae

Development of Dual-Cross-Linked AlgMA/HAMA Hybrid Hydrogels for Traumatic Wound Healing.

Traumatic injuries and uncontrolled, intense bleeding caused by surgery remain among today's leading medical problems. Traumatic wounds are not only observed on the skin but also result from internal organ ruptures caused by explosions and firearms. At this point, severe hemorrhaging can lead to hypothermia, hemorrhagic shock, organ failure, and even death due to the loss of more than 40% of blood volume. Therefore, it is crucial to halt bleeding rapidly. In this study, an alginate derivative that supports platelet aggregation and a hyaluronic acid derivative that adheres to wet tissues and induces angiogenesis, thereby promoting vascularization, have been prepared. The derivatives of alginate and hyaluronic acid were subjected to free radical photopolymerization, allowing them to cross-link in the presence of visible light. The study aims to introduce a new biomaterial featuring sodium alginate and hyaluronic acid groups that demonstrates good mechanical strength, a high swelling capacity to stabilize bleeding in the environment, and effective hemostatic properties. The chemical characterization of biopolymers was analyzed using FTIR and NMR techniques. The mechanical properties, swelling behavior, and degradation profiles of visible light cross-linked hybrid hydrogels were systematically characterized. The biocompatibility of the produced hydrogels was also evaluated using MTT and scratch wound healing tests. In addition, hemolysis and blood coagulation tests were performed to investigate the hemocompatibility and hemostatic potential of visible light cross-linked hybrid hydrogels.

Journal Article

A pancreatic cancer organoid-macrophage co-culture using starPEG-heparin hydrogel deciphers tumor-immune cell interactions.

Macrophages are among the most abundant immune cells in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) and play a key role in regulating the immunosuppressive niche that facilitates tumor growth. Although recent three-dimensional (3D) culture systems using patient-derived materials have advanced our understanding of tumor biology, most models lack key cellular TME components and thus fail to capture tumor-immune cell interactions. To address this gap, we developed an in-vitro 3D co-culture model incorporating PDAC patient-derived organoids (PDOs) and macrophages within a synthetic hydrogel matrix. We optimized culture conditions by tuning medium and matrix conditions to support both cell lineages. Flow cytometry and transcriptomic analyses revealed that initially undifferentiated macrophages adopt an M2-like profile upon exposure to PDAC PDOs in starPEG-heparin hydrogels, mirroring the macrophage phenotypes observed by multiplex immunohistochemistry in the matched primary PDAC tissues. Cytokine secretome profiling revealed PDO-specific differences, indicating distinct underlying macrophage polarization subtypes. Collectively, our starPEG-heparin hydrogel-based 3D co-culture enables hypothesis-driven and physiologically relevant studies of tumor-macrophage interactions and may advance immune-modulatory treatment strategies in patients with PDAC.

Journal Article

Control of the pilocarpine release rate through hydrogels by plasma treatment.

The rate of release of an aqueous solution of pilocarpine hydrochloride sequestered in hydrogel-type materials can be reduced by plasma treatment of the polymer surface. Two plasma techniques were used. The first involves exposure of the hydrogel to the effects of a glow discharge sustained in argon, a process known as CASING. (Crosslinking by Active Species of Inert Gases). The second technique involves the deposition of a thin film by plasma polymerization of organic gases. The gases used in this study were ethane, ethylene and tetrafluoroethylene. Hydrogels were prepared by photopolymerization of 2-hydroxymethyl methacrylate (HEMA), and copolymerization of HEMA with methyl acrylate. The CASING treatment was found to be least effective. The most successful method was the plasma polymerization of tetrafluoroethylene, which yielded an order of magnitude reduction in the flux rate of pilocarpine with a film thickness of 0.25micronm. Polymerization conditions bringing about a crack-resistant film were critical in obtaining the best results.

Delayed-Action Preparations

[Thin soft hydrogel lenses of high and low water (author's transl)].

The authors relate the results obtained with very thin soft hydrogel lenses (0,10 mm thickness) of high and low water content: the Vergo-Softcon THX of 70% water-content and the Bauch and Lomb Plano-T of 38%. The most frequent indications encountered are bullous keratopathy, epithelial defects and keratitis sicca. The results are positive in 78,2% of cases with 70% w/c soft hydrogel lenses. Results are given for cases of direct fitting of thin lenses, as well as for cases of fitting after failures of classic soft hydrogel lenses and in cases of exchanges of 40% lenses for 70% lenses. The 70% water content lenses seem to give better results main in cases of epithelial defects and keratitis sicca.

Contact Lenses, Hydrophilic

Residual astigmatism and visual acuity with hydrogel contact lenses: a comparative study.

Residual astigmatism, visual acuity, and transferred corneal toricity were measured in a double masked fashion on 24 randomly selected patients fitted with Buasch and Lomb Soflens contact lenses, the Hydrocurve II contact lenses, and the AOSoftTM hydrophillic contact lenses. None of the subjects had any contraindications to hydrogel lens wear. All three lens types produced a small but similar reduction in refractive astigmatism. However, because of residual astigmatism, fewer eyes achieved 20/20 or better visual acuity with each of the hydrogel lens types than with the best spectacle correction. Corneal toricity was found to be transferred to the front surface of all three lens types. Our findings indicate that generally these three types of hydrogel lenses result in similar residual astigmatism, visual acuity and transferred corneal toricity. However, individual differences may occur. Therefore, the choice of lens type should be based on the individual patient's response to various lens types.

Adult

Progestin permeation through polymer membranes IV: Mechanism of steroid permeation and functional group contributions to diffusion through hydrogel films.

Hydrogel films were prepared from hydroxyethyl methacrylate, both with (Film II) and withouth (Film I) 5.25 mole% of ethylene glycol dimethacrylate. Permeation, diffusion, and partition coefficients for progesterone, testosterone, nandrolone, norethindrone, 17 alpha-hydroxyprogesterone, estradiol, and hydrocortisone were determined. A solute permeation model was proposed based on the separation of a domain (B) composed of "bulk-like" water and a doman (A) composed of polymer, interfacial water, and bound water present in the films. The separate contributions from the "pore" and "solution-diffusion" mechanisms to the total permeability were calculated from the model. Steroid permeabilities through Films I and II were analyzed in accordance with this model. Permeation of Film II occurred via the solution-diffusion mechanism. Permeation of Film I occurred predominately by the pore mechanism with a small contribution (approximate 20%) from the solution-diffusion mechanism. The latter contribution was dependent on the solubility of the solute within the A domains of the hydrogel film. Functional group contributions to permeation of Film II were ascribed to either steric or hydrogen bonding effects.

Diffusion

Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article

Corneal curvature and refractive error changes associated with wearing hydrogel contact lenses.

To determine if there are corneal curvature and refractive error changes associated with hydrogel lens wear, 27 patients wearing F series Bausch & Lomb SOFLENS-TM contact lenses were examined regularly for nine months. During the first month of lens wear, a mean corneal steepening of 0.23 DK plus or minus 0.18 and an increase in with-the-rule toricity were found, which persisted during the following eight months of wear. A mean increase in myopia of 0.35 DS plus or minus .211 DS was found after nine months of lens wear for five randomly selected patients. This amount of change was statistically significant and was highly correlated with the observed corneal steepening. Their lenses were removed after nine months of lens wear. Both corneal changes and the increase in myopia persisted during the 14 days after lens removal. If long term studies with larger samples show similar results, the effect of hydrogel lenses on corneal curvature and refractive error will have to be considered in the decision to fit this type of lens.

Adult

Rotation of lathe-cut hydrogel lenses on the eye.

The rotation lathe-cut HydroCurveTM gel contact lens was measured on six eyes to evaluate the parameters that influence lens rotation and to determine if this lens could be used to correct astigmatism. Of the 72 observations made, 73.6% showed some lens rotation, and 33.4% of the sample rotated more than 5 degrees per 10 blinks. Of the observations in which rotation was noted, 88.7% were encyclorotation. These results are similar to those found for spin-cast hydrogel lenses. None of the lens parameters evaluated seemed to be related to lens rotation, whereas the eye parameters studied were. Lenses were more likely to rotate on eyes with smaller corneal diameters, smaller palpebral apertures, and corneal curvatures steeper than 4 3.00 DK (X2, N =72, p less than 0.05). Our findings indicate that some method of lens stabilization will be needed before lathe-cut hydrogel lenses can be used to effectively correct astigmatism.

Adult