Search Results (162)

Tissue engineering represents a central strategy in regenerative medicine to restore damaged or missing tissue through structural and functional replacement. In this study, a two-component bioink platform was developed based on amine–anhydride conjugation as a mild crosslinking reaction between synthetic anhydride-containing oligomers (oSMoMA-x) and natural biopolymers. The compatibility of the oligomers with different amine-containing biopolymers, including chitosan, gelatin, and hydrolyzed collagen peptides, was systematically evaluated. To improve cytocompatibility and enable controlled network formation, oSMoMA oligomers with varying anhydride contents were synthesized and characterized, allowing targeted tuning of material properties through comonomer composition. The resulting hydrogels were comparatively assessed with respect to their rheological and physicochemical properties. While hydrogel formation was achieved with all investigated biopolymers, gelatin-based systems exhibited the most favorable characteristics for bioink development. Two gelatin/oSMoMA bioink formulations with distinct gelation behavior were obtained by employing different base catalysts, enabling control over crosslinking kinetics and material properties. Cytocompatibility was comprehensively evaluated using viability assays, demonstrating enhanced metabolic activity of cells encapsulated in gelatin/oSMoMA-3.5 hydrogels compared to established reference systems, with sustained compatibility for up to seven days. Extrusion-based 3D bioprinting was performed using a modified printhead with integrated temperature control to maintain physiological conditions. The bioinks were successfully printed with embedded murine 3T3 fibroblasts, and post-printing analyses confirmed cell proliferation within the hydrogel constructs. Overall, the results demonstrate the broad compatibility of amin–anhydride-crosslinked oSMoMA systems with different biopolymers and highlight gelatin/oSMoMA bioinks as promising cytocompatible materials for stable 3D bioprinting applications in tissue engineering. Full article

Electrical monitoring of brain activity can be performed discreetly and continuously over long periods of time using intra-auricular electroencephalography (intra-auricular EEG), a promising technique suitable for subjects who are difficult to monitor, such as newborns or patients with neurological conditions requiring discreet but long-term neurophysiological assessment. The concept of intra-aural EEG can be realized through the development of systems that include wearable sensors, whose performance critically depends on the development of biocompatible electrode materials that exhibit low impedance and can maintain and provide stable contact between the electrode and the epithelial tissue. Based on our previous work on carbon nanotube (CNT)-based hydrogel composites for intra-aural EEG electrodes, this study focuses on the electrochemical characterization of hydrogels initially prepared from gelatin methacrylate (GelMA)/2-hydroxyethyl methacrylate (HEMA) doped with varying concentrations of CNTs (0–3 wt%). In the present study, the materials obtained in the first stage were evaluated using electrochemical impedance spectroscopy (EIS) under both liquid and dry conditions, supplemented by measurements of hydration capacity. The results show that the composite with 3% CNT content exhibits suitable properties, making the material making the 3 wt% CNT formulation a promising platform for the further development of 3D-printable hydrogel electrodes for intra-aural EEG applications. Equivalent circuit modeling reveals improved ionic and electronic conductivity compared to the undoped hydrogel, attributed to better CNT dispersion and polymer crosslinking. This work provides insights into the structure–property relationships of CNT–hydrogel composites and lays the foundation for the further development of a 3D-printed and in vitro/in vivo validated prototype of intra-aural EEG sensors. Full article

The use of conventional plastics represents a major environmental concern, as approximately 79% ultimately accumulate in landfills or natural ecosystems. Consequently, there is growing interest in the development and application of renewable materials for food packaging. Therefore, the aim of this study was to develop and characterise gelatine-based hydrogels through the incorporation of two amino acids, cysteine and glutamine, thereby contributing to the advancement of safe and environmentally responsible materials. The hydrogels were prepared using the casting method and characterised in terms of their physical and structural properties. The results indicated that the addition of cysteine and glutamine significantly modified the structural, optical, thermal and barrier properties of the gelatine films and hydrogels. Cysteine produced materials with increased opacity, brownish hues and a more hydrophobic surface, changes attributed to the formation of disulphide bonds and the redistribution of non-polar functional groups towards the surface. In contrast, glutamine yielded more transparent and homogeneous films with a more intact internal structure, owing to the development of a more effectively cross-linked and stable polymeric network. Structural (XRD, FTIR) and thermal (TGA, DSC) analyses confirmed that glutamine enhances thermal stability and molecular cohesion, whereas cysteine increases the more ordered structure and rigidity of the matrix. The selection of an appropriate amino acid thus enables the tailoring of functional properties in these biopolymers, representing an effective strategy for their adaptation to biodegradable packaging applications. 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

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are emerging as potent acellular therapeutics; however, their rapid clearance hinders their clinical translation. To address this issue, 3D-bioprinted genipin-crosslinked gelatin (GECL) was engineered for human health. GECL hydrogels were functionalised with human umbilical cord MSC-derived sEVs (hUCMSC-sEVs) to create a bioactive wound-healing platform. These hydrogels demonstrated favourable physicochemical, mechanical, and biodegradable properties while providing an extracellular matrix (ECM)-mimetic environment conducive to tissue regeneration. MSCs were isolated from the umbilical cords, and their small extracellular vesicles (sEVs) were extracted and incorporated into gelatin-based hydrogels via 3D bioprinting. These sEV-loaded scaffolds were embedded in full-thickness wounds in mice, and healing was evaluated through macroscopic observation, histological analysis, collagen deposition, and angiogenesis assessment. Compared with the untreated controls, both the hydrogel-only (B) and sEV-loaded hydrogel (BE) groups significantly accelerated in vivo wound healing. Notably, the BE group achieved complete wound closure within 14 days, restoring the skin architecture, which closely resembled the native tissue with well-organised epidermal and dermal layers, optimal thickness, and skin appendages. Histological and ultrastructural assessments revealed an increased collagen type I deposition, a reduced α-smooth muscle actin (α-SMA) expression, and a robust neovascularisation. The TEM revealed tight junctions and active cellular infiltration, indicating scaffold integration and functional remodelling. Immunohistochemistry further revealed an upregulated CD31 expression with a balanced α-smooth muscle actin (α-SMA) expression, reflecting coordinated angiogenesis and myofibroblast regulation. These results highlight sEV-functionalised GECL hydrogels as robust and clinically translatable acellular therapeutic green products for accelerated wound closure and functional skin regeneration, advancing the fields of regenerative medicine and life expectancy. 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

Peripheral nerve adhesion after surgical injury severely hinders functional nerve regeneration, leading to pain and neurological dysfunction. In this study, we developed a photocrosslinkable methacrylated gelatin (GelMA)-based hydrogel membrane that locally releases dexamethasone to simultaneously prevent adhesion and suppress inflammation. GelMA, synthesized by reacting gelatin with methacrylic anhydride, formed a stable crosslinked network, as confirmed by FT-IR spectroscopy and rheological analysis. Cytocompatibility assays showed that both GelMA and Dexa-GelMA hydrogels were non-cytotoxic to neuronal and fibroblast cell lines. In a Sprague-Dawley (SD) rat sciatic nerve injury model, implantation of the Dexa-GelMA hydrogel significantly reduced perineural adhesion and inflammation compared with the untreated control. Western blot analysis showed an approximately 80% reduction in ED-1 expression, indicating suppression of macrophage activation. Overall, the Dexa-GelMA hydrogel provides a biocompatible, multifunctional platform that integrates physical barrier function with anti-inflammatory drug delivery, showing strong potential for preventing postoperative nerve adhesion and modulating early inflammatory responses in a peripheral nerve injury model. Full article

Effective chronic skin wound healing remains challenging due to excessive inflammation, insufficient vascular support, and impaired extracellular matrix remodeling. By rationally designing and integrating complementary biomaterials, it is possible to synergistically tailor physicochemical properties and biological performance for tissue repair and regeneration. In this study, a gelatin-based composite hydrogel incorporating recombinant type III collagen (rColIII) and carboxymethyl cellulose (CMC) was developed via EDC/NHS-mediated crosslinking and evaluated for wound repair. By tuning the rColIII/CMC ratio, the hydrogel mechanical modulus (G′) increased from ~1.2 kPa to ~2.6 kPa, and enzymatic degradation could be modulated, as reflected by changes in the remaining material mass. The optimized Gel/rCol/CMC-1 formulation supported 3T3 cell migration (1.8-fold increase at 24 h) and promoted a pro-regenerative (M2-like) macrophage phenotype in vitro. In a full-thickness diabetic wound model, Gel/rCol/CMC-1 accelerated wound closure (82.3 ± 4.7% vs. 56.9 ± 5.1% at day 14) and enhanced tissue quality, evidenced by more organized collagen deposition and increased CD31⁺/α-SMA⁺ vessel density. These results demonstrate that formulation-driven tuning of gelatin/rColIII/CMC matrices creates a supportive microenvironment for coordinated wound repair, highlighting their potential as regenerative hydrogel dressings for difficult-to-heal wounds. 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

Despite extensive exploration of gelatin methacryloyl (GelMA)-based hydrogels for bone tissue engineering, their clinical translation is hindered by a critical trade-off: poor precursor stability leads to rapid sedimentation of bioactive fillers like hydroxyapatite (HAp), while formulations optimized for injectability often sacrifice mechanical integrity or handling precision. To overcome this challenge, we report a rheologically engineered, injectable composite hydrogel scaffold that integrates unmodified gelatin as a thermoresponsive viscosity modulator into a GelMA/HAp matrix. The incorporation of gelatin yields a stable, paste-like precursor at physiological temperature, which effectively prevents HAp sedimentation and enables precise, filamentous extrusion. Subsequent UV crosslinking locks the homogeneous structure in place, resulting in a mechanically robust scaffold with significantly enhanced compressive modulus. In vitro studies demonstrate that this biomimetic microenvironment not only supports high viability and proliferation of bone marrow stromal cells (BMSCs) but also potently enhances their osteogenic differentiation, as evidenced by upregulated alkaline phosphatase activity, Runx2 expression, and matrix mineralization. This simple, one-step strategy successfully reconciles injectability, structural fidelity, and bioactivity, offering a highly promising and clinically translatable platform for minimally invasive bone regeneration. Full article

Multifunctional hydrogels with an interpenetrated network structure have shown great potential for biomedical and tissue-regeneration applications. In this work, the biomedical hydrogel was fabricated with an interpenetrated network based on dopamine grafted gelatin (DA-Gel), and genipin crosslinked quaternary ammonium chitosan (QCS), incorporating epigallocatechin gallate (EGCG). The EDC/NHS and Schiff-base bond connections occurred in the hydrogels, as confirmed by Fourier-transform infrared (FT-IR) analysis. The properties of the fabricated hydrogels, including microstructure, degradation rate, adhesive strength, mechanical strength, and rheological behavior, can be regulated by adjusting the DA-Gel/QCS ratio or by using different crosslinking approaches. In addition, the fabricated hydrogels exhibited self-healing properties and strong adhesion to various materials and organs. Furthermore, the hydrogels performed good antibacterial activity against the typical bacteria, Escherichia coli and Staphylococcus aureus. EGCG encapsulated hydrogels displayed excellent antioxidant activities and good hemocompatibility. The hydrogels also demonstrated excellent cytocompatibility and good cell migration ability. The above results provide a facile approach to fabricate the biomedical hydrogels with a regulated network structure and multifunctional characteristics with potential in biomedical applications. Full article

Protein-based hydrogels are increasingly recognized as promising biomaterials for advanced drug delivery, owing to their biocompatibility, biodegradability, and ability to recreate extracellular matrix-like environments. By tailoring the protein source, crosslinking strategy, molecular architecture, and functionalization, these hydrogels can be engineered to mimic the mechanical and biological features of native tissues. Protein-derived hydrogels are currently explored across biomedical and pharmaceutical fields, including drug delivery systems, wound healing, tissue engineering, and, notably, cancer therapy. In recent years, growing attention has been directed toward natural protein hydrogels because of their inherent bioactivity and versatile physicochemical properties. This review provides an updated overview of protein-based hydrogel classification, properties, and fabrication methods. It highlights several widely studied natural proteins, such as gelatin, collagen, silk fibroin, soy protein, casein, and whey protein, that can form hydrogels through physical, chemical, or enzymatic crosslinking. These materials offer tunable mechanical behavior, controllable degradation rates, and abundant functional groups that support efficient drug loading and the development of stimuli-responsive platforms. Furthermore, we examine current advances in their application as drug delivery systems, with particular emphasis on cancer treatment. Protein-based hydrogels have demonstrated the ability to protect therapeutic molecules, provide sustained or targeted release, and enhance therapeutic effectiveness. Although critical challenges, such as batch-to-batch variability, sterilization-induced denaturation, and the requirement for comprehensive long-term immunogenicity assessment, must still be addressed to enable successful translation from preclinical studies to clinical application, ongoing advances in the design and functionalization of natural protein hydrogels highlight their promise as next-generation platforms for precision drug delivery. Full article

Gelatin-based hydrogels are promising materials for pharmaceutical and biomedical applications due to their biocompatibility, biodegradability, and tunable gel-forming behavior. However, their thermo-sensitivity and limited processability often restrict their practical use in advanced drug delivery or tissue engineering systems. In this study, low-molecular-weight gelatin (LMWG) was obtained from native gelatin through controlled degradation with hydroxylamine, aiming to enhance processability while maintaining functional amino groups for crosslinking. Hydrogels prepared from both native gelatin and LMWG were crosslinked with genipin, a natural and biocompatible compound, and comprehensively characterized in terms of structural, mechanical, and biological properties. LMWG exhibited superior processability, remaining liquid at room temperature, which facilitates the preparation of different formulations and the potential incorporation of bioactive compounds into the crosslinked hydrogels. Compared with gelatin-genipin hydrogels, LMWG-genipin hydrogels showed higher swelling capacity, slightly increased porosity, and improved flexibility without significant loss of mechanical integrity. Rheological analysis confirmed both hydrogels’ viscoelastic properties with differences in their thermo-sensitive behavior. Cytocompatibility assays using L929 fibroblasts demonstrated low toxicity as well as proliferation of cells seeded on the materials. Overall, the combination of molecular weight modulation and crosslinking by genipin provides a simple and effective strategy to develop gelatin-based hydrogels suitable for pharmaceutical formulations, tissue-engineering scaffolds, and controlled-release systems. Full article

Owing to their tunable and biocompatible characteristics, collagen- and gelatin-based hydrogels have gained attention in numerous applications, including biomedical, food, pharmaceutical, and environmental. The gelation mechanisms and resulting network structures of collagen and gelatin differ significantly depending on the presence of intra- and intermolecular crosslinks. These differences enable the tailoring of mechanical properties to achieve desired characteristics in the final product. Mechanical gel strength and elasticity determine how effectively hydrogels can mimic natural tissues and respond to deformations. Probing the rheological properties of these gels enables a deeper understanding of their structure, physical attributes, stability, and release profiles. This review provides an in-depth evaluation of the factors affecting the mechanical strength of collagen- and gelatin-based hydrogels, highlighting the influence of co-molecules and the application of physical, chemical, and mechanical treatments. Herewith, it brings insights into how to manipulate the mechanical properties of these gels to improve their end-use functionality. Full article

Hydrogels have attracted considerable attention as biomedical materials owing to their distinctive properties; however, improvements in mechanical strength, biodegradability, and biocompatibility remain essential for advanced clinical applications. This study developed a new dual-crosslinked hydrogel based on gelatin (Gel) and dextran (Dex) via sequential aldimine condensation and photopolymerization. Natural Gel and Dex were functionalized to synthesize methacrylated Gel (GelMA) and oxidized Dex (ODex), respectively. An imine-linked network was initially formed between GelMA and ODex via aldimine condensation, followed by a second crosslinked network generated through blue-light-induced free-radical polymerization of GelMA, yielding dual-crosslinked hydrogels (GMODs). ¹H NMR and FT–IR analyses confirmed the successful functionalization and formation of dual-crosslinked structure. The dual-crosslinked network enhanced the thermal stability and water-retaining capacity of the freeze-dried hydrogels (DGMODs) while reducing the surface wettability and equilibrium swelling ratio of GMODs. The maximum compressive strength (σₘ) increased with crosslinking density; GMOD−2, with moderate crosslinking density, remained intact under 85% compressive strain and achieved σₘ of 108.0 kPa. The degradation rate of GMODs was tunable by adjusting the crosslinking density, thereby modulating their drug-release behavior. GMOD−3, possessing the highest crosslinking density, exhibited effective drug-sustained release for up to five weeks. Biological evaluations, including cytotoxicity assays, live/dead cell staining, and hemolysis tests, verified excellent cytocompatibility (cell survival rate > 92%) and minimal hemolysis ratio (<5%). Furthermore, inhibition zone tests preliminarily revealed moderate antibacterial activity for GMOD−1. The GMOD hydrogels exhibited superior compressive robustness, adjustable biodegradability, and excellent biocompatibility, holding great potential for biomedical applications such as sustained drug-delivery system. Full article