Search Results (129)

Intratumoral injections of macromolecules, such as biologics and immunotherapeutics, show promise in overcoming dose-limiting side effects associated with systemic injections and improve treatment efficacy. However, the retention of injectates in the tumor microenvironment is a major underappreciated challenge. High interstitial pressures and dense tumor architectures create shear forces that rapidly expel low-viscosity solutions post-injection. Injectable hydrogels may address these concerns by providing a viscoelastic delivery vehicle that shields loaded therapies from rapid expulsion from the tumor. A chitosan–glycerol hydrogel was thus developed and characterized with the goal of improving the injection retention of loaded therapeutics. The gelation parameters and mechanical properties of the hydrogel were explored to reveal a shear-thinning gel that is injectable through a 27-gauge needle. Biocompatibility studies demonstrated that the chitosan–glycerol hydrogel was nontoxic. Retention studies revealed significant improvements in the retention of model therapeutics when formulated with the chitosan–glycerol hydrogel compared to less-viscous solutions. Finally, release studies showed that there was a sustained release of model therapeutics of various molecular sizes from the hydrogel. Overall, the chitosan–glycerol hydrogel demonstrated injectability, enhanced retention, biocompatibility, and sustained release of macromolecules, indicating its potential for future clinical use in intratumoral macromolecule delivery. Full article

Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article

The physical and rheological properties of mucilage hydrogels derived from the cladodes of Opuntia ficus-indica (L. Mill) were compared with those of commercial pectin for potential applications in the food industry. All hydrogels—formulated by incorporating sucrose and either calcium chloride or calcium carbonate to promote favorable gel network formation—exhibited pseudoplastic (shear-thinning) behavior. The flow characteristics of the hydrogels prepared with mucilage or pectin conformed to the Casson fluid model. Moreover, all samples consistently displayed loss modulus (G″) values exceeding their corresponding storage modulus (G′) values, indicating a dominant viscous behavior over elastic properties. The ζ-potential of all samples was negative across the pH range studied. Mucilage-based samples exhibited lower ionizability per unit mass and reduced phase stability compared to those containing pectin. Principal component analysis (PCA) revealed that mucilage hydrogels exhibited multivariate profiles similar to pectin hydrogels containing calcium carbonate, though the latter demonstrated greater polydispersity than standard pectic gels. Infrared spectroscopy further highlighted distinct spectral differences between pectins and mucilages, offering valuable insights into their respective functional characteristics. Collectively, these findings underscore the potential of Opuntia ficus-indica mucilages as viable additives in food formulations. Full article

Embedded printing of soft materials relies on yield-stress support matrices to prevent sagging and enable freeform fabrication. The rheological parameters of the matrix material directly influence critical printing outcomes such as strand positioning, cavity formation, structural stability, and defect suppression in embedded printing. Despite widespread use of Carbopol^® formulations, a systematic rheological characterization of ETD2020 across relevant polymer concentrations and pH levels for embedded printing is lacking. Here, we implement a full-factorial design with polymer concentrations from $0.1\mathrm{wt}\%$ to $0.9\mathrm{wt}\%$ and triethanolamine dosages of 30–$50$µL per $100\mathrm{g}$. Steady-shear ($0.001$–$200{\mathrm{s}}^{-1}$) and oscillatory ($1\mathrm{Hz}$) rheometry yielded Herschel–Bulkley parameters ${\tau }_y$, k, n as well as storage and loss modulus $G^{\prime }$/$G^{\prime \prime }$. All formulations exhibited pronounced shear-thinning, with ${\tau }_y$ increasing nonlinearly from <$1\mathrm{Pa}$ to $41.1\mathrm{Pa}$ and $G^{\prime }$ reaching $\approx 400\mathrm{Pa}$ at $0.9\mathrm{wt}\%$. A five-hour window of invariant rheology was identified, followed by a $\Delta {\tau }_y\approx 10\mathrm{Pa}$ increase after five days, indicating delayed polymerization. The comprehensive material characterization defines a rheological window for ETD2020 and facilitates simulation-based modeling and the targeted tuning of matrix properties. Heatmaps provide an interpolated depiction of combined carbomer and triethanolamine concentrations, enabling tunable support matrices for embedded printing. Full article

Electrically conductive hydrogels are gaining attention owing to their applications in biosensing, cellular interfaces, and tissue engineering. However, conventional hydrogels often lack adequate electrical conductivities. Here, we present two novel conductive alginate-based hydrogels designed for extrusion-based 3D bioprinting: (i) covalently synthesized alginate–polypyrrole (alginate–PPy) via EDC/NHS-mediated conjugation with 3-aminopropyl pyrrole, and (ii) nanoparticle-reinforced alginate blended with polypyrrole nanoparticles (alginate@PPy-NP). Both systems exhibited shear-thinning behavior, tunable viscoelasticity, and excellent printability. Alginate@PPy-NP demonstrated superior compressive strength and shape fidelity, whereas alginate–PPy showed enhanced elastic moduli (G′/G″), reflecting a more uniform gel network. Electrical conductivity increased with increasing pyrrole content in both formulations. Optimization of the composition and printing conditions enabled the fabrication of fibroblast-laden constructs with high structural integrity. This work highlights the potential of alginate–polypyrrole hydrogels as customizable, conductive bioinks for 3D bioprinting in regenerative medicine. Full article

The incorporation of solid particles as a filler to a hydrogel is a strategy to modulate its properties for specific applications, or even to introduce new functionalities to the hydrogel itself. The efficacy of such a modification depends on the filler content and its interaction with the hydrogel matrix. In drug delivery applications, solid particles can be added to hydrogels to improve drug loading capacity, enable the inclusion of poorly soluble drugs, and modulate release kinetics. This work focuses on the case of alginate (ALG)-based hydrogels, obtained following an internal gelation procedure using CaCO₃ as the Ca²⁺ source and containing a high solid volume fraction (up to 50%) of metronidazole (MTZ), a drug with low water solubility, as a potential extrusion-based drug delivery system. The impact of the hydrogel precursor composition (ALG and MTZ content) on the rheological behavior of the filled hydrogel and precursor suspension were investigated, as well as the hydrogel stability and MTZ dissolution. In the absence of solid MTZ, the precursor solutions showed a slightly shear thinning behavior, more accentuated with the increase in ALG concentration. The addition of drugs exceeding the saturation concentration in the precursor suspension resulted in a substantial increase (about one order of magnitude) in the low-shear viscosity and, for the highest MTZ loadings, a yield stress. Despite the significant changes, precursor formulations retained their extrudability, as confirmed by both numerical estimates and experimental validation. MTZ particles did not affect the crosslinking of the precursors to form the hydrogel, but they did control its viscoelastic behavior. In unfilled hydrogels, the ALG concentration controls stability (from 70 h for the lowest concentration to 650 h for the highest) upon immersion in acetate buffer at pH 4.5, determining the MTZ release/hydrogel dissolution behavior. The correlations between composition and material properties offer a basis for building predictive models for fine-tuning their composition of highly filled hydrogel systems. Full article

The development of biocompatible, conductive hydrogels via direct ink writing (DIW) has gained increasing attention for strain sensor applications. In this work, a hydrogel matrix composed of polyvinyl alcohol (PVA) and κ-carrageenan (KC) was formulated and enhanced with polyvinylidene fluoride (PVDF) and silver nanoparticles (AgNPs) to impart piezoelectric properties. The ink formulation was optimized to achieve shear-thinning and thixotropic recovery behavior, ensuring printability through extrusion-based 3D printing. The resulting hydrogels exhibited high water uptake (~280–300%) and retained mechanical integrity. Rheological assessments showed that increasing PVDF content improved stiffness without compromising printability. Electrical characterization demonstrated that AgNPs were essential for generating piezoelectric signals under mechanical stress, as PVDF alone was insufficient. While AgNPs did not significantly alter the crystalline phase distribution of PVDF, they enhanced conductivity and signal responsiveness. XRD and SEM-EDX analyses confirmed the presence and uneven distribution of AgNPs within the hydrogel. The optimized ink formulation (5% PVA, 0.94% KC, 6% PVDF) enabled the successful fabrication of functional sensors, highlighting the material’s strong potential for use in wearable or biomedical strain-sensing applications. Full article

The development of printable, conductive, and biocompatible hydrogels has emerged as a promising strategy for the next generation of flexible and soft sensor platforms. In this study, we present a systematic investigation of alginate-based hydrogels incorporating different carbonaceous materials, natural graphite, carbon black (Vulcan V3), and activated carbon (PCO1000C), to evaluate their suitability for sensor applications. Hydrogels were formulated with varying concentrations of sodium alginate and a fixed loading of carbon additives. Each composite was characterized in terms of electrical conductivity under compression, rheological behavior, and mechanical strength. Printability was assessed using a custom-designed extrusion platform that allowed for the precise determination of the minimum force and optimal conditions required to extrude each formulation through a standard 20G nozzle. Among all tested systems, the alginate–graphite hydrogel demonstrated superior extrudability, shear-thinning behavior, and shape fidelity, making it well-suited for 3D printing or direct ink writing. A simple conductivity-testing device was developed to verify the electrical response of each hydrogel in the hydrated state. The effects of different drying methods on the final conductivity were also analyzed, showing that oven drying at 50 °C yielded the highest restoration of conductive pathways. Mechanical tests on printed structures confirmed their ability to maintain shape and resist compressive forces. Finally, the biocompatibility of the printed alginate–graphite hydrogel was validated using a standard cytotoxicity assay. The results demonstrated high cell viability, confirming the material’s potential for use in biomedical sensing environments. This work offers a robust framework for the development of sustainable, printable, and biocompatible conductive hydrogels. The combined performance in printability, mechanical integrity, electrical conductivity, and cytocompatibility highlights their promise for flexible biosensors and wearable sensor technologies. Full article

Background/Objectives: Due to the challenges faced by anticancer therapeutics, such as poor selectivity and metabolic degradation, novel delivery systems are needed to mitigate the adverse effects of chemotherapy. The management of chronic wounds is often overlooked and affects patients mentally and physically. The application of hydrogels can reduce deficiencies in drug delivery and wound healing due to their similarity to the extracellular matrix and stimuli-responsive properties. Methods: A chitosan (CS) hydrogel, cross-linked to gold nanoparticles (AuNPs), followed by the encapsulation of 5-fluorouracil (5-FU), was formulated. The physicochemical properties, drug release profiles, cytotoxicity, and wound healing in vitro were analyzed. Results: Fourier transform infrared spectroscopy and a UV-visible peak at 530 nm confirmed their successful synthesis. Transmission electron microscopy revealed spherical NPs of 89.31 nm, while scanning electron microscopy confirmed the porous network surface of the hydrogels. The thermogravimetric analysis demonstrated enhanced stability for the CS-Au hydrogel, while a non-Newtonian shear-thinning property was evident from rheology. Drug release showed a sustained, pH-dependent release with specificity for the acidic cancer microenvironment. The cytotoxicity assay demonstrated a specificity of the CS-Au-5-FU hydrogel for the cancer cells (HeLa and MCF-7) and diminished cytotoxicity in the non-cancer cells (HEK293). The scratch assay illustrated a complete closure of the wounds in HEK293 cells at low concentrations (15.63 and 31.25 µg/mL). Conclusions: The positive findings from this study confirm the potential of these CS-Au hydrogels to function as smart in vitro delivery systems and scaffolds for wound healing, warranting additional optimizations and in vivo studies. Full article

Background: In tissue engineering, developing injectable hydrogels with tailored mechanical and bioactive properties remains a challenge. This study introduces an injectable hydrogel composite for soft tissue regeneration, composed of oxidized alginate (OA) and N-succinyl chitosan (NSC) cross-linked via Schiff base reaction, reinforced with graphene oxide (GOx) and cyclic arginylglycylaspartic acid (c-RGD). The objective was to create a multifunctional platform combining injectability, bioactivity, and structural stability. Methods: The OA/NSC/GOx-cRGD hydrogel was synthesized through Schiff base cross-linking (aldehyde-amine reaction). Characterization included FTIR (C=N bond at 1650 cm⁻¹), Raman spectroscopy (D/G bands at 1338/1567 cm⁻¹), SEM (porous microstructure), and rheological analysis (shear-thinning behavior). In vitro assays assessed fibroblast viability (MTT) and macrophage TNF-α secretion (ELISA), while ex-vivo injectability and retention were evaluated using chicken cardiac tissue. Results: The hydrogel exhibited shear-thinning behavior (viscosity: 10 to <1 Pa·s) and elastic-dominated mechanics (G′ > G″), ensuring injectability. SEM revealed an interconnected porous structure mimicking native extracellular matrix. Fibroblast viability remained ≥95%, and TNF-α secretion in macrophages decreased by 80% (30 vs. 150 pg/μL in controls), demonstrating biocompatibility and anti-inflammatory effects. The hydrogel adhered stably to cardiac tissue without leakage. Conclusions: The OA/NSC/GOx-cRGD composite integrates injectability, bioactivity, and structural stability, offering a promising scaffold for tissue regeneration. Its modular design allows further functionalization with peptides or growth factors. Future work will focus on translational applications, including scalability and optimization for dynamic biological environments. Full article

Intracanal reinfections continue to pose a major challenge in endodontic treatment. Photodynamic therapy has emerged as a promising antimicrobial strategy. Regarding this, curcumin (CUR), a natural photosensitizer, shows potential in this context, but its application is hampered by poor solubility and rapid degradation. This study aimed to develop and characterize a CUR-loaded nanoparticle-enriched hydrogel to enhance its stability, sustain its release, and evaluate its antimicrobial efficacy upon photoactivation (PhAc). Curcumin-loaded nanoparticles were synthesized and incorporated into a hydrogel matrix, followed by characterization using scanning electron microscopy, Fourier-transform infrared spectroscopy, in vitro CUR release studies, and rheological analysis. Antibiofilm activity against Enterococcus faecalis was assessed under both photoactivated and non-photoactivated conditions. Cytocompatibility was analyzed through fibroblast viability assays and fluorescence staining. The CUR-containing hydrogel demonstrated a sustained release profile extending beyond 72 h. Rheological studies confirmed its shear-thinning behavior, ensuring injectability even after post-photoactivation. Antibiofilm assays revealed a significant reduction in E. faecalis biofilms, with PhAc formulations exhibiting markedly enhanced antibacterial efficacy compared to their non-PhAc counterparts. Cytocompatibility assays confirmed that all formulations, including those subjected to PDT, preserved fibroblast viability, indicating biocompatibility suitable for clinical use. In sum, the CUR-containing hydrogel exhibits properties that support its potential as an effective intracanal therapeutic, combining antimicrobial and photodynamic effects to help prevent reinfections in endodontic treatments. Full article

Background: Vulvar vaginal candidiasis (VVC) is a type of vaginitis resulting from a Candida infection of the vaginal mucosa. Traditional treatments using antibiotics often lead to resistance and disrupt the vaginal microenvironment, causing ongoing problems for patients. In response to these challenges, this study introduces a multifunctional intelligent responsive probiotic hydrogel designed to modulate the vaginal microecological environment to combat Candida albicans infection. Methods: The innovative CMCS-OHA-Lp/Lr hydrogel was formulated using oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS) as carriers, incorporating Lactobacillus plantarum (Lp) and Lactobacillus rhamnosus (Lr) as active components. Comprehensive characterization of the CMCS-OHA-Lp/Lr hydrogel revealed its chemical structure, rheological properties, rapid self-healing properties, gel degradation, and the release of lactobacilli in vitro. Results: The findings demonstrated that the hydrogel’s cross-linking conferred significant physical properties. In addition, the in vitro release study of Lactobacillus showed that the cumulative release rates of Lp and Lr in the medium with pH 5.5 were 83.50 ± 2.70% and 73.31 ± 2.22%, which proved the pH-responsive release characteristics of probiotics in acidic vaginal environments. Furthermore, the storage activity of Lactobacillus indicated that the survival rates of the CMCS-OHA-Lp and CMCS-OHA-Lr hydrogels were 86.90 ± 0.20% and 85.50 ± 0.56%, respectively, proving that encapsulation within the hydrogels significantly enhanced the storage stability of probiotics. In vivo studies further confirmed that the hydrogel alleviated vulval edema symptoms and reduced C. albicans colonies in the vagina, thereby mitigating vaginal inflammation. Conclusions: In conclusion, this pH-responsive, self-healing, and shear-thinning hydrogel offers a promising approach for the clinical treatment of VVC and serves as an effective probiotic delivery vehicle. Full article

The fluorenyl methyl oxycarbonyl phenylalanyl-phenylalanine methyl ester (Fmoc-Phe-Phe-Ome) was synthetized using the liquid phase synthesis strategy. This derivative was separated by hydrophobic interaction chromatography, its purity was analyzed by RP-HPLC and it was characterized by mass spectrometry. This extremely hydrophobic peptide conjugate was incorporated into aqueous solutions of Pluronic^® F127 at low temperatures (below 10 °C). The temperature induced sol–gel transition was investigated by rheological measurements. A delay of the sol–gel transition, caused by the presence of low concentrations of Fmoc-Phe-Phe-Ome (up to 1%), enables better control of the gelation process. The viscoelastic properties of hybrid networks were investigated at 37 °C in different shear conditions. The Pluronic/peptide systems reported herein provide promising alternatives for developing innovative injectable gels as suitable platforms in cancer treatment. Full article

Glycemic management in diabetes patients remains heavily reliant on multiple daily insulin injections, which often leads to poor patient compliance and an elevated risk of hypoglycemia. To overcome these limitations, injectable hydrogels capable of encapsulating insulin within polymeric networks have emerged as a promising alternative. Ideally, a single injection can form an in situ depot that allows prolonged glycemic control and lower injection frequency. This review summarizes recent advances in injectable hydrogels for controlled insulin delivery, focusing on the polymer sources, crosslinking strategies, and stimuli-responsive release mechanisms. Synthetic polymers such as PEG, PNIPAM, and Pluronics dominate the current research due to their highly tunable properties, whereas naturally derived polysaccharides and proteins generally require further modifications for enhanced functionality. The crosslinking types, ranging from relatively weak physical interactions (hydrogen bonds, hydrophobic interactions, etc.) to dynamic covalent bonds with higher binding strength (e.g., Schiff base, phenylboronate ester), significantly influence the shear-thinning behavior and stimuli-responsiveness of hydrogel systems. Hydrogels’ responsiveness to temperature, glucose, pH, and reactive oxygen species has enabled more precise insulin release, offering new options for improved diabetic management. Beyond glycemic regulation, this review also explores insulin-loaded hydrogels for treating complications. Despite the progress, challenges such as burst release, long-term biocompatibility, and scalability remain. Future research should focus on optimizing hydrogel design, supported by robust and comprehensive data. Full article

This study presents the synthesis of allyl-functionalized polysaccharide carbamates (AFCs) with tailored water solubility designed for use in responsive hydrogels and 3D printing applications. A modular one-pot approach was employed to produce cellulose- and xylan-based AFCs, utilizing polysaccharide phenyl carbonates as activated compounds. By fine-tuning the degree of substitution (DS) of functional groups, the water solubility and shear-thinning properties of AFCs were controlled to enhance the gelation and printability. AFC-based hydrogels could be obtained by rapid gelation induced without harmful catalysts through UV irradiation at 365 nm. The materials displayed highly porous and interconnected microstructures, as well as mechanical resilience and high swelling ratios. The hydrogel formation was characterized, and its crosslinking degree was calculated using HR-MAS NMR. The study demonstrated that gelation behavior was sensitive to the pH value, with optimal results under neutral or acidic conditions. Initial 3D printing trials confirmed the material’s rapid shaping capabilities, which is beneficial for biomedical applications and advanced manufacturing of stimuli-responsive materials. Full article