Search Results (31)

Chronic wounds remain a persistent clinical challenge due to delayed healing, recurrent infections, and limited effectiveness of conventional dressings. To address these unmet needs, we designed a multifunctional hydrogel system based on poly(vinyl alcohol) (PVA) and alginate (ALG), incorporating hyaluronic acid (HA)-loaded dipalmitoylphosphatidylcholine (DPPC) liposomes for regenerative stimulation and Aronia-mediated silver nanoparticles (Ag_Aro) for antimicrobial protection. Physicochemical analyses (DLS, SEM, FTIR) confirmed the successful assembly of the system and demonstrated distinct particle sizes, pore morphologies, and structural interactions. Swelling and degradation studies revealed favorable hydration capacity and stability under physiologically relevant conditions. In vitro assays with HaCaT keratinocytes indicated excellent biocompatibility, with HA-liposomes enhancing cell viability to ~190% and Ag_Aro showing minimal cytotoxicity, likely due to polyphenolic surface capping. The combined formulation achieved a balanced swelling profile, controlled degradation, and the highest biocompatibility (~195% viability), underscoring the synergistic benefits of the dual-agent design. This study introduces, to our knowledge, the first PVA–ALG bilayer hydrogel integrating HA-liposomes and phytosynthesized AgNPs, offering a promising platform for advanced wound management. Further in vivo studies are warranted to validate its therapeutic performance. Full article

In this study, the effect of cationic participation on the swelling behavior and pH-responsive release characteristics of polyelectrolyte hydrogel based on gelatin (Gel), sodium alginate (Alg), and carboxymethyl chitosan (CMCS) was explored. The shell–core morphology of the cationic coordination hydrogels was prepared by introducing Na⁺, Ca²⁺, and Fe³⁺ into the crosslinking system, which significantly altered the inherent pH-responsive swelling properties of Gel/Alg-CMCS hydrogel. The modified hydrogel demonstrated a release resistance of carvacrol (CAR) under acidic conditions while facilitating rapid release under neutral conditions. Notably, the CAR release profile was substantially modified by the distinct anti-swelling properties of cationic coordination hydrogels. In particular, Gel/Alg-CMCS-Fe³⁺ hydrogel exhibited high accumulative release of 58.34% at pH 1.0 while maintaining a minimal release degree of merely 7% in weakly acidic and neutral environments. These intriguing findings provide valuable insights into intelligent active delivery for future applications. Full article

This study aimed to develop and characterise novel hydrogels based on natural bioactive compounds for topical antimicrobial applications. Four gel systems were formulated using different polymers, namely polyacrylic acid (Carbopol 940, CBP-G), chitosan with high and medium molecular weights (CTH-G and CTM-G), and sodium alginate (ALG-G), incorporating tinctures of Verbena officinalis and Aloysia triphylla, Laurus nobilis essential oil, and a β-cyclodextrin–clove essential oil complex. All gels displayed a homogeneous macroscopic appearance and maintained stability for over 90 days. Rheological studies demonstrated gel-like behaviour for CBP-G and ALG-G, with well-defined linear viscoelastic regions and distinct yield points, while CTM-G exhibited viscoelastic liquid-like properties. SEM imaging confirmed uniform and continuous matrices, supporting controlled active compound distribution. Thermogravimetric analysis (TG-DTA) revealed a two-step degradation profile for all gels, characterised by high thermal stability up to 230 °C and near-total decomposition by 500 °C. FTIR spectra confirmed the incorporation of bioactive compounds and products and highlighted varying interaction strengths with polymer matrices, which were stronger in CBP-G and CTH-G. Antimicrobial evaluation demonstrated that chitosan-based gels exhibited the most potent inhibitory and antibiofilm effects (MIC = 2.34 mg/mL) and a cytocompatibility assessment on HaCaT keratinocytes showed enhanced cell viability for chitosan gels and dose-dependent cytotoxicity for alginate formulations at high concentrations. Overall, chitosan-based gels displayed the most favourable combination of stability, antimicrobial activity, and biocompatibility, suggesting their potential for topical pharmaceutical use. 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

One of the emergent regenerative treatments for the restoration of the articular cartilage is tissue engineering (TE), in which hydrogels can functionally imitate the extracellular matrix (ECM) of the native tissue and create an optimal microenvironment for the restoration of the defective tissue. Hyaluronic acid (HA) is known for its potential in the field of TE as a regenerative material for many tissues. It is one of the major components of the articular cartilage ECM contributing to cell proliferation and migration. HA is the only non-sulphated glycosaminoglycan (GAG). However, herein, we use a HA presenting a high amount of sulphated glycosaminoglycans (sGAGs), altering the intrinsic properties of the material particularly in terms of biological response. Alginate (Alg) is another polysaccharide widely used in TE that allows stiff and stable hydrogels to be obtained when crosslinked with CaCl₂. Taking the benefit of the favourable characteristics of each biomaterial, semi-interpenetrating (semi-IPN) hydrogels had been developed by the combination of both materials, in which alginate is gelled, and HA remains uncrosslinked within the hydrogel. Varying the concentration of alginate and HA, the final rheological, viscoelastic, and mechanical properties of the hydrogel can be tailored, always seeking a trade-off between biological and physico-mechanical properties. All developed semi-IPN hydrogels have great potential for biomedical applications. Full article

This study presents the synthesis, characterization, and evaluation of hybrid hydrogels based on calcium alginate (Ca-Alg) and synthetic nanoclay LaponiteRD (Lap), with an emphasis on their swelling and sorption properties. The motivation behind the development of these hybrid hydrogels stems from the need for sustainable materials with enhanced mechanical strength, swelling properties, and sorption capacity for environmental remediation and controlled-release applications. Synthesis methods for the ionotropically cross-linked Ca-Alg hydrogel and Alg–Lap composite hydrogels, based on Alg and Lap in the form of granules and fibres, have been developed. The Fourier-transform infrared spectroscopy (FTIR), Energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analyses of composite hydrogels confirmed the successful incorporation of Lap into the Ca-Alg matrix, indicating strong interactions between the polymer and clay, which enhanced the structural integrity of the hydrogels. The morphology of the surface and pore structure of nanocomposites were studied using Scanning Electron Microscopy (SEM). The swelling behaviour of the nanocomposites was largely dependent on the concentrations of Lap and the cross-linking agent (CaCl₂), with higher concentrations leading to more rigid, less swellable structures due to the increased cross-linking density. The sorption studies, specifically with Fe(II) ions, demonstrated that the hybrid hydrogels possess a large sorption capacity, with Lap contributing to selective sorption at lower Fe(II) ion concentrations and Alg enhancing overall capacity at higher concentrations. This suggests that the synergistic interaction between Alg and Lap not only improves mechanical stability but also tailors the sorption properties of the hydrogels. These findings position the Alg-Lap hydrogels as promising materials for a range of environmental applications, including wastewater treatment, heavy metal ion removal, and the design of advanced filtration systems. The study’s insights into the tunability of these hydrogels pave the way for further research into their use in diverse fields such as biomedicine, agriculture, and industrial water management. Full article

Alginate/gelatin (Alg-Gel) hydrogels have been used experimentally, associated with mesenchymal stromal/stem cells (MSCs), to guide bone tissue formation. One of the main challenges for clinical application is optimizing Alg-Gel stiffness to guide osteogenesis. In this study, we investigated how Alg-Gel stiffness could modulate the dental pulp stem cell (DPSC) attachment, morphology, proliferation, and osteogenic differentiation, identifying the optimal conditions to uncouple osteogenesis from the other cell behaviors. An array of Alg-Gel hydrogels was prepared by casting different percentages of alginate and gelatin cross-linked with 2% CaCl₂. We have selected two hydrogels: one with a stiffness of 11 ± 1 kPa, referred to as “low-stiffness hydrogel”, formed by 2% alginate and 8% gelatin, and the other with a stiffness of 55 ± 3 kPa, referred to as “high-stiffness hydrogel”, formed by 8% alginate and 12% gelatin. Hydrogel analyses showed that the average swelling rates were 20 ± 3% for the low-stiffness hydrogels and 35 ± 2% for the high-stiffness hydrogels. The degradation percentage was 47 ± 5% and 18 ± 2% for the low- and high-stiffness hydrogels, respectively. Both hydrogel types showed homogeneous surface shape and protein (Alg-Gel) interaction with CaCl₂ as assessed by physicochemical characterization. Cell culture showed good adhesion of the DPSCs to the hydrogels and proliferation. Furthermore, better osteogenic activity, determined by ALP activity and ARS staining, was obtained with high-stiffness hydrogels (8% alginate and 12% gelatin). In summary, this study confirms the possibility of characterizing and optimizing the stiffness of Alg-Gel gel to guide osteogenesis in vitro without altering the other cellular properties of DPSCs. Full article

Shape-shifting polymers usually require not only reversible stimuli-responsive ability, but also strong mechanical properties. A novel shape-shifting photochromic hydrogel system was designed and fabricated by embedding hydrophobic spiropyran (SP) into double polymeric network (DN) through micellar copolymerisation. Here, sodium alginate (Alg) and poly acrylate-co-methyl acrylate-co-spiropyran (P(SA-co-MA-co-SPMA)) were employed as the first network and the second network, respectively, to realise high mechanical strength. After being soaked in the CaCl₂ solution, the carboxyl groups in the system underwent metal complexation with Ca²⁺ to enhance the hydrogel. Moreover, after the hydrogel was exposed to UV-light, the closed isomer of spiropyran in the hydrogel network could be converted into an open zwitterionic isomer merocyanine (MC), which was considered to interact with Ca²⁺ ions. Interestingly, Ca²⁺ and UV-light responsive programmable shape of the copolymer hydrogel could recover to its original form via immersion in pure water. Given its excellent metal ion and UV light stimuli-responsive and mechanical properties, the hydrogel has potential applications in the field of soft actuators. Full article

Autologous fat grafting is hampered by unpredictable outcomes due to high tissue resorption. Hydrogels based on enzymatically pretreated tunicate nanocellulose (ETC) and alginate (ALG) are biocompatible, safe, and present physiochemical properties capable of promoting cell survival. Here, we compared in situ and ex situ crosslinking of ETC/ALG hydrogels combined with lipoaspirate human adipose tissue (LAT) to generate an injectable formulation capable of retaining dimensional stability in vivo. We performed in situ crosslinking using two different approaches; inducing Ca²⁺ release from CaCO₃ microparticles (CMPs) and physiologically available Ca²⁺ in vivo. Additionally, we generated ex situ-crosslinked, 3D-bioprinted hydrogel-fat grafts. We found that in vitro optimization generated a CMP-crosslinking system with comparable stiffness to ex situ-crosslinked gels. Comparison of outcomes following in vivo injection of each respective crosslinked hydrogel revealed that after 30 days, in situ crosslinking generated fat grafts with less shape retention than 3D-bioprinted constructs that had undergone ex situ crosslinking. However, CMP addition improved fat-cell distribution and cell survival relative to grafts dependent on physiological Ca²⁺ alone. These findings suggested that in situ crosslinking using CMP might promote the dimensional stability of injectable fat-hydrogel grafts, although 3D bioprinting with ex situ crosslinking more effectively ensured proper shape stability in vivo. Full article

In this paper, sodium alginate (NaAlg) was used as functional monomers, bovine serum albumin (BSA) was used as template molecules, and calcium chloride (CaCl₂) aqueous solution was used as a cross-linking agent to prepare BSA molecularly imprinted carboxylated multi-wall carbon nanotubes (CMWCNT)/CaAlg hydrogel films (MIPs) and non-imprinted hydrogel films (NIPs). The adsorption capacity of the MIP film for BSA was 27.23 mg/g and the imprinting efficiency was 2.73. The MIP and NIP hydrogel film were loaded on the surface of the printed electrode, and electrochemical performance tests were carried out by electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) using the electrochemical workstation. The loaded MIP film and NIP film effectively improved the electrochemical signal of the bare carbon electrode. When the pH value of the Tris HCl elution solution was 7.4, the elution time was 15 min and the adsorption time was 15 min, and the peak currents of MIP-modified electrodes and NIP-modified electrodes reached their maximum values. There was a specific interaction between MIP-modified electrodes and BSA, exhibiting specific recognition for BSA. In addition, the MIP-modified electrodes had good anti-interference, reusability, stability, and reproducibility. The detection limit (LOD) was 5.6 × 10⁻⁶ mg mL⁻¹. Full article

The synthesis and physicochemical properties of hydrogels with interpenetrated physical and chemical networks were considered in relation to their prospective application as biomimetic materials in biomedicine and bioengineering. The study was focused on combined hydrogels based on natural polysaccharide—calcium alginate (CaAlg) and a synthetic polymer–polyacrylamide (PAAm). The series of hydrogels with varying proportions among alginate and polyacrylamide have been synthesized, and their water uptake has been characterized depending on their composition. The equilibrium swelling and re-swelling in water after drying were considered. The compatibility of alginate and polyacrylamide in the combined blend was studied by the thermodynamic approach. It showed a controversial combination of negative enthalpy of mixing among PAAm and CaAlg with positive Gibbs energy of mixing. Mechanical and electrical properties of the combined gels with double networking were studied as relevant for their prospective use as scaffolds for tissue regeneration and working bodies in actuators. The storage modulus and the loss modulus were determined in the oscillatory compression mode as a function of proportions among natural and synthetic polymers. Both moduli substantially increased with the content of CaAlg and PAAm. The electrical (Donnan) potential of hydrogels was measured using the capillary electrode technique. The Donnan potential was negative at all compositions of hydrogels, and its absolute values increased with the content of CaAlg and PAAm. Full article

The process of bone regeneration is complicated, and it is still a major clinical challenge to regenerate critical-size bone defects caused by severe trauma, infection, and tumor resection. Intracellular metabolism has been found to play an important role in the cell fate decision of skeletal progenitor cells. GW9508, a potent agonist of the free fatty acid receptors GPR40 and GPR120, appears to have a dual effect of inhibiting osteoclastogenesis and promoting osteogenesis by regulating intracellular metabolism. Hence, in this study, GW9508 was loaded on a scaffold based on biomimetic construction principles to facilitate the bone regeneration process. Through 3D printing and ion crosslinking, hybrid inorganic-organic implantation scaffolds were obtained after integrating 3D-printed β-TCP/CaSiO₃ scaffolds with a Col/Alg/HA hydrogel. The 3D-printed β-TCP/CaSiO₃ scaffolds had an interconnected porous structure that simulated the porous structure and mineral microenvironment of bone, and the hydrogel network shared similar physicochemical properties with the extracellular matrix. The final osteogenic complex was obtained after GW9508 was loaded into the hybrid inorganic-organic scaffold. To investigate the biological effects of the obtained osteogenic complex, in vitro studies and a rat cranial critical-size bone defect model were utilized. Metabolomics analysis was conducted to explore the preliminary mechanism. The results showed that 50 μM GW9508 facilitated osteogenic differentiation by upregulating osteogenic genes, including Alp, Runx2, Osterix, and Spp1 in vitro. The GW9508-loaded osteogenic complex enhanced osteogenic protein secretion and facilitated new bone formation in vivo. Finally, the results from metabolomics analysis suggested that GW9508 promoted stem cell differentiation and bone formation through multiple intracellular metabolism pathways, including purine and pyrimidine metabolism, amino acid metabolism, glutathione metabolism, and taurine and hypotaurine metabolism. This study provides a new approach to address the challenge of critical-size bone defects. Full article

Caffeine (CAF) is a psychostimulant present in many beverages and with rapid bioabsorption. For this reason, matrices that effectuate the sustained release of a low amount of CAF would help reduce the intake frequency and side effects caused by high doses of this stimulant. Thus, in this study, CAF was loaded into magnetic gelatin/alginate (Gel/Alg/MNP) hydrogels at 18.5 mg/g_hydrogel. The in vitro release of CAF was evaluated in the absence and presence of an external magnetic field (EMF) and Ca²⁺. In all cases, the presence of Ca²⁺ (0.002 M) retarded the release of CAF due to favorable interactions between them. Remarkably, the release of CAF from Gel/Alg/MNP in PBS/CaCl₂ (0.002 M) at 37 °C under an EMF was more sustained due to synergic effects. In PBS/CaCl₂ (0.002 M) and at 37 °C, the amounts of CAF released after 45 min from Gel/Alg and Gel/Alg/MNP/EMF were 8.3 ± 0.2 mg/g_hydrogel and 6.1 ± 0.8 mg/g_hydrogel, respectively. The concentration of CAF released from Gel/Alg and Gel/Alg/MNP hydrogels amounted to ~0.35 mM, thereby promoting an increase in cell viability for 48 h. Gel/Alg and Gel/Alg/MNP hydrogels can be applied as reservoirs to release CAF at suitable concentrations, thus forestalling possible side effects and improving the viability of SH-SY5Y cells. Full article

Hydrogel-based dressings exhibit suitable features for successful wound healing, including flexibility, high water-vapor permeability and moisture retention, and exudate absorption capacity. Moreover, enriching the hydrogel matrix with additional therapeutic components has the potential to generate synergistic results. Thus, the present study centered on diabetic wound healing using a Matrigel-enriched alginate hydrogel embedded with polylactic acid (PLA) microspheres containing hydrogen peroxide (H₂O₂). The synthesis and physicochemical characterization of the samples, performed to evidence their compositional and microstructural features, swelling, and oxygen-entrapping capacity, were reported. For investigating the three-fold goal of the designed dressings (i.e., releasing oxygen at the wound site and maintaining a moist environment for faster healing, ensuring the absorption of a significant amount of exudate, and providing biocompatibility), in vivo biological tests on wounds of diabetic mice were approached. Evaluating multiple aspects during the healing process, the obtained composite material proved its efficiency for wound dressing applications by accelerating wound healing and promoting angiogenesis in diabetic skin injuries. Full article

The hybrid hydrogel materials meet important social challenges, including the photocatalytic purification of water and bio-medical applications. Here, we demonstrate two scenarios of polyacrylamide-TiO₂ (PAAm@TiO₂) composite hydrogel design using calcium alginate (Alg-Ca) or Keplerate-type polyoxometalates (POMs) {Mo₁₃₂} tuning the polymer network structure. Calcium alginate molding allowed us to produce polyacrylamide-based beads with an interpenetrating network filled with TiO₂ nanoparticles Alg-Ca@PAAm@TiO₂, demonstrating the photocatalytic activity towards the methyl orange dye bleaching. Contrastingly, in the presence of the POM, the biocompatible PAAm@TiO₂@Mo₁₃₂ composite hydrogel was produced through the photo-polymerization approach (under 365 nm UV light) using vitamin B2 as initiator. For both types of the synthesized hydrogels, the thermodynamic compatibility, swelling and photocatalytic behavior were studied. The influence of the hydrogel composition on its structure and the mesh size of its network were evaluated using the Flory–Rehner equation. The proposed synthetic strategies for the composite hydrogel production can be easily scaled up to the industrial manufacturing of the photocatalytic hydrogel beads suitable for the water treatment purposes or the biocompatible hydrogel patch for medical application. Full article