Search Results (393)

Developing multifunctional wound dressings with excellent mechanical properties, strong tissue adhesion, and efficient antibacterial activity is crucial for promoting wound healing. This study prepared a novel nanocomposite hydrogel dressing based on sodium alginate-polyacrylic acid dual crosslinking networks, incorporating tannic acid-coated cellulose nanocrystals (TA@CNC) and in-situ reduced silver nanoparticles for multifunctional enhancement. The rigid CNC framework significantly improved mechanical properties (elastic modulus of 146 kPa at 1 wt%), while TA catechol groups provided excellent adhesion (36.4 kPa to pigskin, 122% improvement over pure system) through dynamic hydrogen bonding and coordination interactions. TA served as a green reducing agent for uniform AgNPs loading, with CNC negative charges preventing particle aggregation. Antibacterial studies revealed synergistic effects between TA-induced membrane disruption and Ag⁺-triggered reactive oxygen species generation, achieving >99.5% inhibition against Staphylococcus aureus and Escherichia coli. The TA@CNC-regulated porous structure balanced swelling performance and water vapor transmission, facilitating wound exudate management and moist healing. This composite hydrogel successfully integrates mechanical toughness, tissue adhesion, antibacterial activity, and biocompatibility, providing a novel strategy for advanced wound dressing development. Full article

According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

Fe³⁺-incorporated hydrogels are particularly valuable for wearable devices due to their tunable mechanical properties and ionic conductivity. However, conventional immersion-based fabrication fundamentally limits hydrogel performance because of heterogeneous ion distribution, ionic leaching, and scalability limitations. To overcome these challenges, we report a novel one-pot strategy where controlled amounts of Fe³⁺ are directly added to polyacrylamide-sodium acrylate (PAM-SA) precursor solutions, ensuring homogeneous ion distribution. Combining this with Photoinduced Electron/Energy Transfer Reversible Addition–Fragmentation Chain Transfer (PET-RAFT) polymerization enables efficient hydrogel fabrication under open-vessel conditions, improving its scalability. Fe³⁺ concentration achieves unprecedented modulation of mechanical properties: Young’s modulus (10 to 150 kPa), toughness (0.26 to 2.3 MJ/m³), and strain at break (800% to 2500%). The hydrogels also exhibit excellent compressibility (90% strain recovery), energy dissipation (>90% dissipation efficiency at optimal Fe³⁺ levels), and universal adhesion to diverse surfaces (plastic, metal, PTFE, and cardboard). Finally, these Fe³⁺-incorporated hydrogels demonstrated high effectiveness as strain sensors for monitoring finger/elbow movements, with gauge factors dependent on composition. This work provides a scalable, oxygen-tolerant route to tunable hydrogels for advanced wearable devices. Full article

Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article

At emergency sites, bacteria in the environment can cause secondary wound infections. Timely treatment of infected wounds can improve the prognosis. In this study, we designed a closed-loop system for real-time wound infection monitoring and electronically controlled drug release, enabling rapid and stable deployment at disaster sites. Multilayer screen-printed electrodes were developed to detect uric acid (UA), pH, and temperature biomarkers. The electrode’s outermost layer was shielded by a zwitterionic conductive hydrogel (Gel) to prevent environmental interference and achieve systematic antibacterial protection through in situ reduction of silver nanoparticles (AgNPs) on its surface. For rapid and efficient drug delivery, amikacin (Ami) loaded cationic liposomes (Lipo) embedded in the zwitterionic conductive hydrogel (Gel-Lipo@Ami) were integrated as the core therapeutic carrier. This closed-loop system provides timely infection detection and enables in situ treatment during emergency rescues. Full article

Background/Objectives: Glioblastoma (GBM) remains the most aggressive primary brain tumor, characterized by high malignancy, recurrence rate, and dismal prognosis, thereby demanding innovative therapeutic strategies. In this study, we report a novel in situ targeting inclusion complex hydrogel hybrid system (DOX/RGD-CD@Gel) that integrates doxorubicin (DOX) with RGD-conjugated cyclodextrin (RGD-CD) and a thermosensitive hydrogel for enhanced GBM therapy. Methods: The DOX/RGD-CD@Gel system was prepared by conjugating doxorubicin (DOX) with RGD-modified cyclodextrin (RGD-CD) and embedding it into a thermosensitive hydrogel. The drug delivery and antitumor efficacy of this system were evaluated in vitro and in vivo. Results: In vitro and in vivo evaluations demonstrated that DOX/RGD-CD@Gel significantly enhanced cytotoxicity compared to free DOX or DOX/CD formulations. The targeted delivery system effectively promoted apoptosis and inhibited cell proliferation and metastasis in GBM cells. Moreover, the hydrogel-based system exhibited prolonged drug retention in the brain, as evidenced by its temperature- and pH-responsive release characteristics. In a GBM mouse model, DOX/RGD-CD@Gel significantly suppressed tumor growth and improved survival rates. Conclusions: This study presents a paradigm of integrating a targeted inclusion complex with a thermosensitive hydrogel, offering a safe and efficacious strategy for localized GBM therapy with potential translational value. Full article

Postoperative adhesions are a prevalent complication following abdominal surgeries, often leading to significant clinical challenges. This study introduces an innovative solution utilizing a polyethylene glycol (PEG)-based triblock copolymer to form an injectable, self-healing hydrogel aimed at preventing these adhesions. The hydrogel, formulated with temperature-responsive and self-healing properties through the incorporation of poly (N-isopropyl acrylamide) (PNIPAM) and anion–pi interactions, was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The hydrogel’s physical properties, biocompatibility, hemostatic effect, and anti-adhesive capabilities were rigorously tested through in vitro and in vivo experiments involving rat models. It demonstrated excellent biocompatibility, effective tissue adhesion, and robust hemostatic properties. Most notably, it exhibited significant anti-adhesive effects in a rat abdominal wall–cecum model, reducing adhesion formation effectively compared to controls. The PEG-based injectable hydrogel presents a promising approach for postoperative adhesion prevention. Its ability to gel in situ triggered by body heat, coupled with its self-healing properties, provides a substantial advantage in clinical settings, indicating its potential utility as a novel anti-adhesion material. Full article

Antimicrobial resistance arises from treatment non-adherence and ineffective delivery systems. Optimal wound dressings combine localized drug release, exudate management, and bacterial encapsulation through hydrogel-forming nanofibers for enhanced therapy. In this work, polylactic acid (PLA) and polyvinylpyrrolidone (PVP) fibers loaded with chlorhexidine (CHX) were developed using Solution Blow Spinning (SBS), a scalable electrospinning alternative that enables in situ deposition. Molecular interactions between CHX and polymers in solution (by UV-Vis and fluorescence spectroscopy) and in solid state (by FTIR, XRD and thermal analysis) were studied. The morphology of the polymeric fibers was determined by optical microscopy, showing that PVP fibers are thinner (1625 nm) and more uniform than those of PLA (2237 nm). Finally, drug release from single-polymer fibers discs, overlapping fibers discs (PLA/PVP/PLA and PVP/PLA/PVP), and solid dispersions was determined by UV-Vis spectrometry. PVP-based fibers exhibited faster CHX release due to their hydrophilic nature, while PLA fibers proved sustained release, attributed to their hydrophobic matrix. This study highlights the potential of PLA/PVP-CHX fibers made from SBS as advanced wound dressings, combining biocompatibility and personalized drug delivery, offering a promising platform for localized and controlled antibiotic delivery. Full article

Infectious wounds pose formidable clinical challenges due to hypoxia, exacerbated inflammation, and persistent microbial colonization. To address this, we developed a bioinspired multifunctional hydrogel (PTDPs) through the in situ freeze-thaw co-assembly of polyvinyl alcohol (PVA), tea polyphenols (TP), polydopamine (PDA), and marine-derived self-assembling peptides (AAPs). The resultant PTDP hydrogel formed an intricate hydrogen-bonded network that enhanced mechanical robustness and substrate adhesion. TP and PDA synergistically confer potent antioxidant properties: TP scavenges radicals via phenolic hydroxyl groups while PDA enhances responsiveness to diverse radicals in hypoxic environments. Integrated with AAPs’ pro-regenerative functions and PDA’s broad-spectrum antimicrobial efficacy, this system generates therapeutic synergy. Characterization revealed outstanding physicochemical properties including tunable plasticity, high swelling ratios, and sustained hydration retention. In vitro studies demonstrated potent antioxidant activity, efficient inhibition of Staphylococcus aureus and Escherichia coli proliferation, and cytocompatibility facilitating endothelial cell migration/proliferation. In murine full-thickness infected wound models, the PTDP hydrogel significantly accelerated wound closure, enhanced neovascularization, and improved collagen deposition, underscoring its potential as an innovative therapeutic platform for infected and chronic wounds with strong translational prospects. Full article

This study proposes a simple yet versatile microfluidic strategy for fabricating monodisperse alginate hydrogel microspheres using a symmetric flow-focusing device. The system integrates three key innovations: (1) Cost-effective mold fabrication: A paper-based positive master replaces conventional SU-8 photoresist, significantly simplifying device prototyping. (2) Surfactant-free droplet generation: Alginate hydrogel droplets are formed at the first flow-focusing junction without requiring interfacial stabilizers. (3) In situ solidification with coalescence suppression: Acetic acid-infused corn oil is introduced at the adjacent junction, simultaneously triggering ionic crosslinking of alginate via pH reduction while preventing droplet aggregation. Notably, the hydrogel microspheres can be efficiently harvested through oscillatory aqueous phase separation, removing post-fabrication washing steps (typically 6–8 cycles for surfactant and oil removal). This integrated approach demonstrates exceptional advantages in fabrication simplicity, process scalability, and operational robustness for high-throughput hydrogel microsphere production. Full article

Gelatin, a biocompatible and biodegradable polymer, has garnered considerable attention in tissue engineering (TE) due to its diverse applications enabled by its tunable physical properties. Among the various strategies employed for the fabrication of gelatin-based hydrogels, the use of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂) as a catalytic system has been highlighted as an effective tool for producing hydrogels with highly modifiable properties. Herein, we explore recent progress in the utilization of the HRP/H₂O₂ catalytic system for the creation of gelatin-based hydrogels, with an emphasis on TE applications. Particular attention has been given to the interplay between variations in the concentration equilibrium of HRP and H₂O₂ and the fine-tuning of gel properties tailored for various TE applications. Emerging trends, such as in situ gelation and hybrid bioinks, have also been examined through the lens of their prospective applications, extrapolating from the findings in cell cultures and animal models. A comprehensive review of two databases (Scopus and Web of Science) was conducted. The data extracted from each study included the materials used for each application, methods used for material preparation, cells used in the TE application, laboratory animals used, and whether computational/simulation techniques were implemented. The applications included both homopolymeric hydrogels, using only gelatin as the backbone, and copolymeric hydrogels, with ≥2 polymers. Full article

Multifunctional hydrogels represent an emerging technological advancement in cancer therapeutics, integrating diagnostic imaging capabilities with therapeutic modalities into comprehensive, multifunctional systems. These hydrogels exhibit exceptional biocompatibility, biodegradability, high water retention capacity, and tunable mechanical properties, enabling precise drug delivery while minimizing systemic side effects. Recent innovations in stimuli-responsive components facilitate intelligent, controlled drug release mechanisms triggered by various stimuli, including changes in pH, temperature, magnetic fields, and near-infrared irradiation. Incorporating diagnostic imaging agents, such as magnetic nanoparticles, fluorescent dyes, and radiolabeled isotopes, substantially improves tumor visualization and real-time therapeutic monitoring. Multifunctional hydrogels effectively integrate chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, and their synergistic combinations, demonstrating superior therapeutic outcomes compared to conventional methods. Particularly, injectable and in situ-forming hydrogels provide sustained local drug delivery postoperatively, effectively reducing tumor recurrence. However, challenges persist, including initial burst release, mechanical instability, regulatory barriers, and scalability concerns. Current research emphasizes advanced nanocomposite formulations, biofunctionalization strategies, and innovative manufacturing technologies like 3D bioprinting to facilitate clinical translation. This review comprehensively summarizes recent advancements, clinical applications, and future perspectives of multifunctional hydrogel systems for enhanced cancer treatment, underscoring their potential to revolutionize personalized oncology. Full article

A platform of two-component cross-linked hydrogel (cGEL) based on gelatinous peptides and anhydride-containing cross-linkers (oPNMA, oPDMA) is extended for use in peripheral nerve regeneration. Hybrid composites with bio-/chemical cues for enhanced biophysical and biochemical properties were fabricated by covalently grafting small molecular, heterobifunctional amines including the nerve growth factor mimetic LM11A-31 to the oligomeric cross-linkers prior to hydrogel formation. The cytocompatibility and growth-supportive conditions within the matrix are confirmed for pristine and modified hydrogels using L929 mouse fibroblasts and human adipose-derived stem cells (hASCs). For hASCs, cell behavior depends on the type of cross-linker and integrated amine. In a subsequent step, neonatal rat Schwann cells (SCs) are seeded on pristine and functionalized cGEL to investigate the materials’ capabilities to support SC growth and morphology. Within all formulations, cell viability, adherence, and cell extension are maintained though the cell elongation and orientation vary compared to the two-dimensional control. It is possible to merge adjustable two-component hydrogels with amines as biochemical signals, leading to improved nervous cell proliferation and activity. This indicates the potential of tunable bioactive cGEL as biomaterials in nerve implants, suggesting their use as a foundational component for nerve conduits. Full article