Search Results (205)

The lack of accessible in vitro 3D bone tissue models puts developing countries at a disadvantage in terms of research capacity and healthcare access. In this study, a decellularized corn cob scaffold was functionalized with GTMAC by adding quaternary ammonium groups and coating it with an alginate–gelatin hydrogel to promote mesenchymal stem cell adhesion, offering a low-cost platform for bone disease modeling. Systematic characterization of the scaffold demonstrated that decellularization reduced DNA content by over 80%. Chemical treatment affected the mechanical properties of the matrix, while the hydrogel coating and the functionalized surface of the scaffold promoted cell adhesion and morphology comparable to that observed in 3D cell cultures. MTT analysis showed a subtle reduction in metabolic signal in functionalized scaffolds, which may reflect changes in cell distribution and adhesion within the 3D matrix rather than cytotoxic effects. Full article

Porous hydrogels are critical for tissue engineering and regenerative medicine, as they mimic the native extracellular matrix to support cell infiltration and mass transport. A common strategy for engineering pore structures involves the incorporation and subsequent removal of sacrificial porogen templates (e.g., crystals or microspheres). Although this approach offers excellent control over pore architecture, it often suffers from complex procedures and biosafety concerns arising from incomplete template removal. In this work, we present a simple, biocompatible, and versatile templating approach. By systematically investigating the coacervation parameters, we produced gelatin microspheres (GSs) with tunable diameters from 7 µm to 300 µm via a green, instrument-free, and scalable process. Using GSs of 20–160 µm as porogens, we obtained alginate hydrogels with adjustable viscoelasticity, stiffness, and pore sizes. We then validated two cell-loading strategies for bulk porous alginate hydrogels using immortalized human T (Jurkat) cells: (i) post-seeding into pre-formed pores supported high-density, long-term, and organized cell aggregates with >90% viability; (ii) in situ encapsulation (prior to pore formation) yielded >80% viability and preserved the cluster-forming growth characteristics of Jurkat cells. Moreover, composites of smaller GSs (7–20 µm) with alginate could be syringe-extruded into stable, sub-millimeter porous filaments, demonstrating the potential for 3D printing. Collectively, this work provides a promising platform for three-dimensional culture of immune cells. Full article

Background: This study investigates a novel alginate–gelatin hydrogel incorporating polyphenol-rich grape skin extract as a multifunctional therapeutic system for diabetic wound healing. The extract was obtained by ultrasound-assisted extraction and formulated into a biopolymer hydrogel designed to combine optimal moisture retention with the controlled release of bioactive compounds. Methods: A streptozotocin-induced diabetic rat model was used to evaluate wound contraction, collagen deposition, oxidative stress parameters, and systemic inflammatory markers over a 15-day period. Animals were assigned to four groups: untreated control, silver sulfadiazine (SSD), empty hydrogel (EH), and extract-loaded hydrogel (LH). Results: The LH formulation demonstrated superior wound closure, reaching 97.1% by day 15, significantly outperforming SSD and other groups. Hydroxyproline levels were markedly elevated in LH-treated tissues, indicating enhanced collagen synthesis and extracellular matrix formation. Redox analyses revealed substantial reductions in TBARS and significant increases in SOD, CAT, and GSH, confirming the strong antioxidative activity of the incorporated extract. Moreover, LH treatment produced pronounced decreases in IL-6 and TNF-α, restoring inflammatory balance and facilitating timely progression from the inflammatory to proliferative phase. Conclusions: These effects are attributed to the synergistic actions of grape skin polyphenols which exerted broad biochemical and structural benefits essential for diabetic wound repair. Overall, this sustainable, bioactive hydrogel represents a promising alternative for advanced wound care. Full article

Gelatin–alginate composite hydrogels are some of the most prevalent bioinks used for extrusion-based three-dimensional (3D) bioprinting because of their combined bioactivity and ability to ionically crosslink. Ionically crosslinked gelatin–alginate constructs containing human bone marrow–derived mesenchymal stem cells (hBM-MSCs) were characterised over time under standardised in vitro conditions to assess physicochemical properties and resultant cell behaviour. Water uptake and degradation were quantified over time in phosphate-buffered saline (PBS) and collagenase type II media for up to 21 days. Cell viability and metabolic activity were quantified, and osteogenic gene expression (RUNX2, COL1A1, OCN) was assessed. Raman spectroscopy and compressive mechanical characterisation were performed. Collagen and glycosaminoglycan-related peaks were observed from extracellular matrix (ECM)-associated components, with an increased presence of protein-associated signatures later in culture. Hydrogels displayed nonlinear elastic behaviour with increased stress after longer incubation times, suggesting no degradation of mechanical integrity over the duration of the study. Hydrogels experienced rapid hydration followed by decreased swelling over time, with a maximum swelling ratio at 24 h. Degradation rates significantly increased over longer incubation times (p < 0.001) and in collagenase media compared to PBS (p < 0.001). Observed differences were likely due to both ion-exchange-mediated network disassembly and the dissolution of gelatin components. Cell metabolic activity decreased under osteogenic culture conditions, while changes in osteogenic marker expression were sequential, suggesting a transition from proliferation to early osteogenic commitment in this 3D system. This work provides both physicochemical and biological characterisation of a commonly utilised gelatin–alginate bioink system, to provide future optimisations within the field of extrusion-based bone tissue engineering, a reproducible baseline for future optimisation of bioink systems in extrusion-based bone tissue engineering. Full article

This study evaluated whether three-dimensional alginate–gelatin hydrogels (AGHs) crosslinked with calcium chloride (CaCl₂) enhance the osteo-odontogenic differentiation of odontoblast-like cells in vitro. Two seeding configurations were compared: inter-hydrogel (INT) surface seeding and intra-hydrogel (INTR) encapsulation. Here, the MDPC-23 cells were cultured in AGHs crosslinked with 70 or 100 mM CaCl₂ and assessed for proliferation, cytoskeletal morphology, alkaline phosphatase (ALPase) activity, osteo-odontogenic gene expression, and mineralized nodule formation. After 7 days, cell proliferation was significantly greater in the alginate–gelatin hydrogel (AGH) groups than in the control group. Cells in the intra alginate–gelatin hydrogel 100 (INTR-AGH100) remained predominantly rounded, whereas those in the inter alginate–gelatin hydrogel 100 (INT-AGH100) formed irregular clusters on the hydrogel surface. ALPase activity was highest in INTR-AGH100 at the early stage of culture. Both INT-AGH100 and INTR-AGH100 showed significantly increased expression of DSPP, DMP-1, BSP, OCN, OPN, and Runx-2, together with enhanced mineralized nodule formation. Although no significant differences were detected between the two seeding strategies in all assays, distinct morphological patterns were observed, and the INTR configuration showed relatively greater early differentiation-related activity. These findings suggest that 100 mM CaCl₂-crosslinked AGHs provide a favorable three-dimensional microenvironment under the present experimental conditions and represent a promising in vitro scaffold platform to support future studies of scaffold-guided dentin regeneration. Full article

Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up. Full article

Radiotherapy is essential for treating head and neck cancer but frequently leads to radiation-induced fibrosis (RIF) in salivary glands (SGs). RIF develops through a cascade of radiation-triggered events, including DNA damage, excessive oxidative stress, and epithelial cell death. Persistent injury can cause cells to become senescent and release inflammatory signals, fueling chronic inflammation. These processes activate pathways, particularly TGF-β/SMAD, resulting in fibroblast activation, myofibroblast differentiation, and extracellular matrix accumulation. Potential treatments include drugs, mesenchymal stem/stromal cell (MSC) therapy, and gene-transfer approaches. In which, MSC therapy is particularly promising as MSCs can migrate to injured tissue and support epithelial regeneration. Yet progress is limited by the difficulty of expanding human acinar cells (ACs) in vitro. To address this gap, tunable alginate–gelatin–hyaluronic acid (AGHA) bioink hydrogels have emerged as a suitable system as gelatin provides adhesion sites for AC attachment and 3D organoid formation, alginate offers tunable mechanical support through ionic crosslinking, and hyaluronic acid contributes essential cues for cell adhesion, migration, and morphogenesis. The aim of this review is to synthesize current understanding of the mechanisms driving RIF, evaluate available therapeutic strategies, and highlight the role of AGHA in generating engineered SG constructs to test MSC therapies for RIF. Full article

Cartilage regeneration remains an unmet clinical challenge. Despite the great advances in the production of hydrogels as support matrices for cartilage regeneration, the resulting mechanical properties remain low. Granular composite hydrogels appear as ideal candidates due to their injectability and modularity in design. Here, we report on the fabrication and characterization of heterogeneous composite granular hydrogels based on methacrylated chitosan (CHIMA) and gelatin (GelMA) microparticles supported by an interstitial methacrylated alginate (ALMA) matrix. Microparticles were prepared by an oil-emulsion method and their size and morphology optimized, resulting in CHIMA and GelMA microparticles of 10.8 µm (95% CI 9.2, 13.1) and 115.8 µm (95% CI 107.5, 137.6) in diameter, respectively. The microparticles were mixed with ALMA and crosslinked to form granular hydrogels that demonstrated reduced swelling and weight loss. The storage modulus increased from 33 to 66.4 kPa for CHIMA/ALMA hydrogels and from 11.5 to 19.5 kPa for GelMA/ALMA hydrogels when the particle concentration increased from 10 to 50%, and was higher than traditional ALMA hydrogels. Hydrogels of 50:50 CHIMA:GelMA permitted a 6.6-fold increase in cell number after 28 days of culture, and promoted the chondrogenic differentiation of embedded mouse mesenchymal stem cells with a glycosaminoglycan deposition of over 15 µg and the expression of chondrogenic markers. Full article

Hydrogels constructed from natural biomacromolecules with multifunctional properties, such as improved mechanical strength, ionic stability, biocompatibility, and ionic conductivity, are highly desirable for advanced food and biomedical applications, yet remain challenging to design. Although alginate is one of the most widely used hydrogel-forming polysaccharides due to its biocompatibility and gelation ability, its intrinsic limitations often hinder the development of hydrogels with fully optimized performance. This review provides a systematic comparison of alginate-based composite hydrogels formed with complementary biopolymers, including whey proteins, gelatin, pectin, starch, and chitosan, focusing on their synergistic effects on structural, mechanical, and functional properties. Recent studies are critically analyzed to elucidate how polymer–polymer interactions influence gel network formation, environmental ionic stability, and encapsulation performance. Particular attention is given to fabrication strategies and formulation parameters that enhance the immobilization and controlled release of probiotics, vitamins, polyphenols, and other bioactive compounds. By integrating current knowledge on structure–function relationships and processing approaches, this review offers practical design guidelines for the development of multifunctional alginate-based hydrogel systems for applications in functional foods and nutraceutical delivery. Full article

Hydrogels have emerged as promising functional materials for improving water management and nutrient delivery in agriculture, particularly under conditions of increasing water scarcity and declining soil fertility. However, most commercially available superabsorbent hydrogels are based on petroleum-derived polymers, raising concerns regarding their persistence in soils, potential microplastic formation and long-term environmental impact. In response, significant research efforts are being directed toward the development of biodegradable hydrogels derived from renewable biopolymers. This review provides a critical overview of recent advances in hydrogel systems designed for agricultural applications, with a particular focus on biopolymer-based materials. First, the current landscape of hydrogel technologies used as soil conditioners and controlled-release systems for agrochemicals is contextualized, highlighting the limitations of conventional synthetic hydrogels. Subsequently, the main classes of natural polymers explored for hydrogel fabrication, including polysaccharides (e.g., chitosan, alginate, cellulose and starch) and proteins (e.g., gelatin, keratin and soy protein), are analyzed in terms of raw material sources, gelation mechanisms and structure–property relationships. Their performance in key agricultural functions, such as water retention, controlled nutrient release, soil conditioning and enhancement of plant growth, is also discussed. Finally, the review identifies major challenges that currently hinder large-scale implementation, including mechanical stability, degradation behavior in complex soil environments, nutrient release control and economic scalability. By integrating recent progress and outlining emerging research directions, this work aims to support the rational design of next-generation biodegradable hydrogels capable of contributing to sustainable agriculture and circular bioeconomy strategies. Full article

Bone regeneration focuses on the creation of functional tissue to repair bone defects. Creating a biodegradable scaffold hydrogel that combines a hemostatic agent with bioactive ceramics can afford the biological and mechanical benefits of both components. In the present study, we developed an injectable gelatin–alginate dual-composite hydrogel, loaded with two functional fillers: hydroxyapatite (HA) and the hemostatic agent montmorillonite (MMT). HA (microparticles and nanoparticles) was incorporated at concentrations of 10–30 mg/mL, with and without MMT at 20 mg/mL. The effects of functional fillers and their concentration on the microstructure and resulting physical and mechanical properties were studied, and a qualitative model summarising these effects was developed. All formulations exhibited clinically appropriate gelation times (5–29 s). n-HA significantly prolonged gelation time, reaching 29 ± 3 s at 30 mg/mL, while MMT reduced gelation time at all concentrations. The tensile strength of the unloaded hydrogel reached 20 kPa and increased to 57 kPa with 30 mg/mL of n-HA. The tensile strength even increased further with the addition of MMT (77 kPa). The results indicate that the combination of HA and MMT produced dual micro-composite hydrogels with moderate reinforcement, whereas the combination of n-HA and MMT generated dual nano–micro composites with combined reinforcing effects. The latter exhibited the highest strength and sealing ability while maintaining clinically relevant gelation times and controlled swelling behaviour. In conclusion, the combination of MMT with n-HA or HA enables the creation of functional hydrogels with controlled properties, tailored to specific applications in bone regeneration. Full article

Biopolymer adhesives are moving toward frontline use in medicine and manufacturing as the limitations in some petrochemical systems, including cytotoxicity, challenges in wet adhesion for specific families of synthetic resins and formaldehyde emissions associated with amino-formaldehyde materials are becoming increasingly difficult to accept. This review integrates mechanisms, material classes and quantitative performance across biopolymer-based adhesives. We focus on architectures that combine permanent covalent anchoring with reversible, energy-dissipating bonds and on how functional group density, crosslink density, microstructure and additives act as design knobs for wet performance, durability and degradation. Across biomedical applications, chitosan, alginate, gelatin and related hydrogels achieve wet lap-shear strengths on the order of tens of kilopascals, cut liver-bleeding times by roughly half, provide strong antibacterial activity and close diabetic wounds by about 92 percent by day 14. Thermoresponsive alginate–gelatin sealants exceed clinically relevant burst pressures and microneedle patches withstand more than 120 mmHg while sealing arteries in under a minute. In industrial settings, dialdehyde-based starch resins deliver 0.83 to 1.05 MPa dry shear and maintain strength after water immersion while meeting stringent emission classes, and silane-modified nanocellulose in urea–formaldehyde markedly reduces free formaldehyde without sacrificing the internal bond. We conclude by identifying priorities for standardized wet testing, and lifetime matching of strength and degradation that can support large-scale clinical and industrial translation. Full article

A major objective of this study is to investigate the incorporation of hydroxyapatite nanoparticles (nHA) in a biopolymeric matrix of alginate (Alg) and gelatin (Gel), with particular emphasis understanding how controlled variation in nHA concentration affects rheological, mechanical, printing, and biological performance. Although Alg–Gel blends and nHA-containing hydrogels have been previously explored, a systematic and quantitative correlation between nHA loading, viscoelastic recovery, yield behavior, filament fidelity, and cell viability under optimized bioprinting conditions has not been established. Here, we address this by preparing and evaluating six composite inks (0, 1, 2, 3, 4, and 5% w/v nHA). The parameters of interest included the printing accuracy, the rheological profile, including over 70% viscosity recovery after 10 s in almost all formulations, the elastic modulus, which was over 10 kPa, and the swelling degree. In addition, pre-osteoblastic cells were embedded in these formulations, subsequently bioprinted, and demonstrated viability over 70% after 7 days. The results advance our understanding on the effect of the chemical composition behind the modification of the properties of the composite materials and their applications for biofabrication. This work contributes quantitative insight into how compositional tuning influences the performance of alginate–gelatin–nHA bioinks for extrusion-based bioprinting applications. Full article

Inflammatory bowel disease (IBD) arises from chronic dysregulation at the epithelial–stromal interface, creating a need for in vitro systems that better capture these interactions. In this study, we developed a 3D co-culture platform in which HT-29 intestinal epithelial cells and IMR-90 fibroblasts are embedded within an alginate–gelatin hydrogel, alongside a complementary interface model using a plasma-treated electrospun mesh to spatially compartmentalize stromal and epithelial layers. We first assessed metabolic activity, viability, and proliferation across several epithelial-to-fibroblast ratios and identified 1:0.5 as the most supportive of epithelial expansion. The A1G7 hydrogel maintained high viability (>92%) and sustained growth in all mono- and co-cultures. To evaluate inflammatory competence, models were stimulated with lipopolysaccharide (LPS), administered either within the hydrogel or through the culture medium. LPS exposure increased TNF-α and IL-1β secretion in both configurations, with the magnitude of the response depending on the delivery route. Treatment with dexamethasone consistently reduced cytokine levels, confirming the model’s suitability for pharmacological testing. Together, these results demonstrate that the alginate–gelatin system provides a reproducible epithelial–stromal platform with quantifiable inflammatory readouts, offering a practical foundation for mechanistic studies and early-stage screening of anti-inflammatory therapeutics in IBD. Full article

The osteochondral interface (OCI) is a structurally and functionally complex tissue whose degeneration or injury often results in poor healing and joint dysfunction due to its avascular and hypocellular nature. Conventional surgical treatments remain suboptimal, prompting growing interest in regenerative approaches, particularly with the utilization of hydrogel-based biomaterials that can mimic the extracellular matrix and support osteochondral regeneration. This study reviewed types of hydrogels, scaffold processing techniques, and animal models for OCI regeneration. Our search demonstrated that gelatin, alginate, chitosan, and hyaluronic acid were the most frequently investigated hydrogels. Layered constructs dominated current scaffold designs, while advanced methods such as 3D printing and extrusion demonstrated unique potential to create graded architectures resembling the native OCI. Rabbits were the most widely used in vivo models, though translation will require larger animal studies with clinically relevant defect sizes. Future efforts should focus on developing mechanically reinforced, biologically active, and continuously graded hydrogels, supported by standardized preclinical validation in large-animal models, to accelerate translation toward clinical solutions for osteochondral regeneration. Full article