Search Results (1,179)

Rapid hemostasis, oxidative stress resistance, and minimally invasive administration are crucial performance requirements for high-performance wound covering. Inspired by the dynamic remodeling properties of the native extracellular matrix, we fabricated a multifunctional injectable hydrogel through dynamic Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS), combined with magnesium ion (Mg²⁺) coordination. The effects of Mg²⁺ content on hydrogel properties were systematically investigated. The hydrogels gelled rapidly under physiological conditions and showed good injectability, self-healing behavior, and favorable adhesion to moist tissues. Notably, Mg²⁺ incorporation significantly enhanced hemostatic performance in a mouse tail amputation model, reducing blood loss from 391.7 mg to approximately 75 mg and shortening hemostasis time from 151.7 s to 50.3 s. The 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging efficiency reached approximately 80%, and the hydrogel effectively scavenged intracellular reactive oxygen species (ROS) without compromising cytocompatibility or fibroblast activity. This study presents a biomimetic and easily prepared hydrogel platform that integrates pro-coagulant activity, redox regulation, and on-demand injectability, showing translational potential as bioactive wound covering for bleeding control and oxidative microenvironment regulation. Full article

Background and Objectives: The main neurodegenerative diseases (NDs)—Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS)—represent a growing global health burden with no available disease-modifying therapies. Curcumin, a polyphenol from Curcuma longa, is a promising candidate owing to its pleiotropic antioxidant, anti-inflammatory, and neuroprotective profile observed mainly in preclinical models, but the poor oral bioavailability (<1%) and negligible BBB penetration (<0.1%) have substantially limited curcumin’s clinical translation. The objective of this work was to critically examine the therapeutic potential of curcumin in NDs, focusing on advanced drug delivery systems (DDSs) designed to overcome its pharmacokinetic barriers. Methods: This is a narrative, non-systematic review of PubMed/MEDLINE, Scopus, and Web of Science. The review is organized around five complementary thematic areas selected to span the full translational pipeline of curcumin in neurodegeneration, from mechanistic rationale to clinical applicability: (1) molecular mechanisms, addressing the pleiotropic activities that justify therapeutic interest; (2) pharmacokinetic barriers, the principal obstacle to clinical translation; (3) the evolution of drug delivery systems (DDSs), documenting the technological strategies developed to overcome these barriers; (4) disease-specific applications, evaluating the available evidence across the four main NDs; and (5) translational limitations, identifying the methodological and regulatory gaps that must be closed to enable clinical implementation. Results: Curcumin exhibits neuroprotective activity in preclinical models of the four NDs analysed, acting on six interconnected mechanisms and the gut–brain axis. Four generations of DDSs have been developed, from phytosomes and clinically used lipid dispersions (Meriva^®, BCM-95^®, Longvida^®, and Theracurmin^®) to fourth-generation systems (biomimetic nanoparticles, MOFs, microneedles, 3D scaffolds, hydrogels, and carbon dots) that substantially increase the bioavailability in preclinical studies. Combination strategies, such as curcumin with resveratrol and dutasteride, show preliminary clinical signals in ALS. However, clinical translation remains limited: over 80% of positive animal findings have not been replicated in humans, formulation characterization is frequently incomplete, and most trials lack CNS-exposure biomarkers. Importantly, most of the reported bioavailability claims are based on total curcumin measurements (parent aglycone plus its inactive Phase II conjugates) rather than the active aglycone alone, a methodological limitation that should be considered when interpreting the magnitude of the bioavailability improvements reported for novel formulations. Conclusions: Curcumin exhibits pleiotropic neuroprotective activity in preclinical models of AD, PD, MS, and ALS, mediated by interconnected antioxidant, anti-inflammatory, anti-amyloidogenic, mitochondrial, and gut–brain axis mechanisms. However, its poor systemic bioavailability (<1%), minimal blood–brain barrier penetration, and extensive first-pass metabolism have limited clinical translation. Advanced drug delivery systems (including lipid-based carriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles (PLGA and chitosan), and bioinspired vesicles (exosomes)) are essential in order to overcome these barriers. Nevertheless, the formulation heterogeneity, limited long-term safety data, and reliance on preclinical models remain major obstacles; a definitive clinical translation will therefore require well-characterized formulations validated in phase II/III trials with cerebrospinal fluid exposure biomarkers, the pharmacokinetic monitoring of active aglycone (rather than total curcumin including inactive conjugates), and adaptive trial designs in neurological populations. Full article

For the first time, for oxidative cross-linking of chitosan with a natural polyphenol, ferulic acid, the so-called small two-domain bacterial laccase, was used. Recombinant Streptomyces carpinensis laccase (ScaSL) has been shown to oxidize ferulic acid in neutral and alkaline environments, which is important for subsequent nucleophilic reactions of chitosan with oxidation products. The selected conditions (pH 7.0, molar ratio FA/NH₂ = 1:10) provide a cross-linking degree of more than 80%, which significantly exceeds the indicators previously achieved using other laccases. Based on the results of quantum chemical modeling and experimental studies using FTIR spectroscopy and XPS, as well as thermogravimetric and differential scanning calorimetry, a new mechanism for laccase-catalyzed cross-linking of chitosan with ferulic acid without the formation of Schiff bases is proposed. The resulting hydrogels have a uniform smooth microstructure, high oxygen permeability, a significant degree of swelling (270%), and stability over a wide pH range. The material neutralizes up to 95% of ABTS^+• cation radicals. Quantum chemical analysis within the framework of the Marcus theory has demonstrated that the chitosan–ferulic acid conjugate is superior in antioxidant capacity to ferulic acid dimers, despite the decrease in the matrix element of the bond. Application of two-domain bacterial laccase for modifying chitosan hydrogels with ferulic acid opens the way to the creation of environmentally friendly biomaterials with antioxidant protection. Full article

Bioadhesive hydrogels combine tissue-adhesive properties with therapeutic multifunctionality, offering promising solutions for regenerative medicine. This comprehensive review examines the design strategies, fundamental adhesion mechanisms, and clinical applications of these biomaterials. We systematically discuss four primary adhesion mechanisms: physical interactions, chemical adhesion, topological mechanical interlocking, and bioinspired adhesion. Key design parameters, including wet-environment adhesion strength, self-healing capability, injectability, and controlled biodegradability, are analyzed and benchmarked against commercial products. Major material platforms, encompassing catechol-based systems, chitosan derivatives, gelatin/GelMA variants, Polyethylene glycol (PEG)-based adhesives, and multi-network hybrid systems, are evaluated for their adhesive performance and functional integration. Tissue-specific applications spanning wound healing, bone/cartilage repair, soft tissue sealing, vascular repair, and neural regeneration are critically assessed, emphasizing in vivo outcomes and clinical translation barriers. Finally, we discuss emerging frontiers, including artificial intelligence-guided material design, on-demand detachable adhesives, and regulatory pathways. Synthesizing over 140 peer-reviewed references from the past two decades, this review provides a systematic roadmap from fundamental adhesion science toward the clinical implementation of next-generation bioadhesive hydrogels. Full article

Hydrogels are hydrated three-dimensional polymeric networks with biomedical potential because they can encapsulate therapeutic agents and provide localised, sustained, or stimulus-responsive drug delivery. Their performance is determined by interacting variables, including polymer composition, synthesis route, crosslinking chemistry, drug loading, swelling, degradation, and the biological microenvironment. This multidimensional design space often makes hydrogel development slow and dependent on trial-and-error experimentation. This review examines the data-driven development of biomedical hydrogels for controlled drug delivery, focusing on clinical applications and emerging machine-learning approaches that support material selection, formulation design, synthesis optimisation, and release prediction. The review first discusses natural and synthetic hydrogels, including alginate, chitosan, gelatin-based systems, hyaluronic acid, and polyethylene glycol, with emphasis on how their physicochemical properties influence biocompatibility, synthesis flexibility, and drug-release behaviour. Key applications are then considered, including wound healing, cancer therapy, glucose-responsive insulin delivery, and inflammatory disease management. Particular attention is given to injectable and stimuli-responsive hydrogels, where formulation conditions and synthesis parameters can be tuned to improve localisation, therapeutic exposure, and release control. The review evaluates machine-learning methods, including random forest, gradient boosting, artificial neural networks, Gaussian process regression, and active learning, for predicting hydrogel properties, modelling release profiles, optimizing synthesis and formulation variables, and prioritizing experimental candidates. Finally, translational challenges are addressed, including small non-standardised datasets, limited external validation, weak in vitro-clinical correlations, material safety, explainability, reproducibility, scalability, and regulatory requirements. By integrating clinical, materials, synthesis, and machine-learning perspectives, this review highlights opportunities for developing safer and clinically relevant hydrogel-based drug-delivery systems. Full article

Efficient cutaneous wound healing relies on the phenotypic transition of macrophages toward an anti-inflammatory, pro-reparative M2-like state. Non-healing chronic wounds are pathologically characterized by the breakdown of this polarization balance. In this review, we synthesize recent research on biomaterials fabricated from naturally occurring polysaccharides with intrinsic immunomodulatory activity, mainly represented by hydrogels that modulate macrophage phenotypic transitions. We first dissect the immune microenvironment of wound healing and elaborate on the core regulatory networks governing M1/M2 polarization, with a particular focus on signaling pathways and metabolic reprogramming. On this basis, we classify pro-M2 natural polysaccharides into mannose-containing and mannose-free categories according to their core structural motifs that mediate immunomodulatory activity, and detail their molecular mechanisms, including pattern recognition receptor engagement (MR, Dectin-1, CD44, etc.) and downstream signaling cascades (STAT6, PI3K/Akt, NF-κB, etc.). Representative polysaccharides such as konjac glucomannan (KGM), Ganoderma lucidum polysaccharide (GLP), chitosan (CS) and hyaluronic acid (HA) are discussed with a clarified structure–activity relationship (SAR). Finally, we highlight emerging design strategies for multi-functional immunomodulatory hydrogels, including mechano-biochemical coupling platforms and spatiotemporally controlled delivery systems, and analyze ongoing controversies and translational bottlenecks in this field. The relationship between material structure and function enables the rational design of purpose-built polysaccharide dressings that regulate immunity. This review highlights these materials as promising preclinical platforms for chronic wound management, although their clinical translation requires further validation. Full article

Injectable thermoresponsive hydrogels are useful for localized drug delivery because they can be administered as low-viscosity formulations and then form, or reinforce, therapeutic depots directly at diseased tissue sites. Their common design principle is a temperature-dependent transition from a flowable formulation before administration to an in situ matrix at physiological temperature, or a thermally regulated change in swelling, mesh size, drug-matrix affinity or degradation. This review focuses on thermoresponsive injectable systems for localized delivery, including PNIPAM-based systems, poloxamers/Pluronics, PEG/polyester block copolymers, polyurethane-based hydrogels, chitosan-based thermogels, hyaluronan- and glycosaminoglycan-based systems, and selected multicomponent or nanocomposite networks. The in vivo application areas considered are local cancer therapy, wound healing and antibacterial treatment, osteoarthritis and intra-articular delivery, and myocardial infarction/cardiac repair. Across these indications, preclinical studies suggest that thermoresponsive hydrogels may prolong local residence time, reduce systemic exposure, enhance delivery of poorly soluble or unstable payloads, and modulate disease-specific microenvironments. Remaining challenges include gelation control, mechanical stability, degradation products, immune response, sterilization, manufacturing reproducibility, disease heterogeneity and robust translational validation. Full article

Cancer remains a major global health concern, driving the search for safe and effective bioactive compounds from natural sources. Jujube peel red pigment (JP), an anthocyanin-rich extract, has shown preliminary bioactivity, yet its antitumor potential and delivery challenges remain underexplored. This study systematically evaluated the in vitro antitumor activity of JP and developed a thermosensitive hydrogel-based local delivery system (JP-H) to overcome its rapid diffusion and poor retention. JP exhibited selective cytotoxicity against HeLa cervical cancer and B16 melanoma cells, with no obvious toxicity to normal L929 and RAW264.7 cells. In HeLa cells, JP exerted antitumor effects by initiating mitochondrial-dependent apoptosis accompanied by elevated expression of Bax and cleaved Caspase-9/-3 as well as decreased Bcl-2 level, and arrested cell cycle at the G1/S phase by regulating CCND1, CDK2, CDK4, PCNA, MYC and TP53. To enable localized delivery, JP was incorporated into an injectable chitosan/gelatin/F127 thermosensitive hydrogel (JP-H), which exhibited rapid sol-gel transition at physiological temperature, shear-thinning behavior, and a porous microstructure. JP-H not only sustained JP release but also significantly enhanced antibacterial activity against E. coli and S. aureus compared to free JP. Furthermore, JP-H markedly inhibited HeLa cell migration and induced superior apoptotic/necrotic cell death in co-culture assays, outperforming free JP. Collectively, this work establishes JP as a multi-target antitumor agent and demonstrates JP-H as a promising local therapeutic platform combining sustained delivery, antibacterial protection, and enhanced anticancer efficacy for cervical cancer treatment. Full article

The growing interest in bio-based and bioactive materials, as well as sustainable production techniques, has driven the development of multifunctional hybrid systems. This study reports the fabrication of novel microcapsules with a double-layer alginate–PEG–chitosan shell, with or without a core, via coaxial electrospraying, followed by ionotropic gelation and polyelectrolyte complexation. PEG1000 and PEG1500 were incorporated into the shell as phase change materials, and thyme oil–oleic acid served as a hydrophobic bioactive core. Scanning electron microscopy and Fourier transform infrared analyses confirmed the structural integrity and effective shell–core integration. Thermogravimetric analyses showed enhanced thermal stability in double-layer alginate–PEG–chitosan biopolymer network shell and thyme oil included core system, with a delayed degradation up to 370.0 °C and reduced mass loss compared to the alginate–chitosan control sample. Differential scanning calorimetry over ten heating–cooling cycles demonstrated significant phase transition enthalpies (70.5–91.8 J·g⁻¹ at 37.6–48.5 °C), confirming efficient thermal energy storage and release governed by the PEG content. Aqueous suspensions prepared from microcapsules exhibited reversible temperature-dependent swelling–deswelling behavior between 20.0 and 55.0 °C, governed by hydrogel properties of the alginate–chitosan shell interactions. The microcapsules exhibited pronounced pH-dependent swelling (enhanced at pH 7.0), high water solubility, and good antioxidant activity. These findings highlight the broad application potential of bio-based shell–core microcapsules, e.g., active food packaging, biomedical dressings, protective coatings, pharmaceutical and biomedical delivery systems and functional textiles. Full article

Agarose is a thermoreversible, highly biocompatible polysaccharide increasingly used in tissue engineering (TE). Its molecular architecture, optical clarity, tunable mechanics, and chemical inertness make agarose hydrogels attractive scaffolds for generating bioartificial tissues by TE. This review summarizes current knowledge on agarose extraction, purification, structural variants, and physicochemical properties regarding gelation behavior, stiffness, porosity, and bioactivity. We discuss how agarose type and concentration critically determine hydrogel biomechanical and optical performance, influencing cell behavior and in vivo suitability. Although biologically inert, agarose can be functionalized or combined with fibrin, collagen, chitosan, and other biomaterials to enhance cell adhesion, proliferation, and differentiation. Diverse biofabrication approaches—including micromolding, bead production, 3D bioprinting, and de novo assembly of cells, biomaterials and bioactive factors—have enabled the generation of microtissues, organoids, and complex multilayered constructs. Agarose-based biomaterials allowed for the successful generation of bioartificial substitutes of cartilage, bone, adipose tissue, skin, cornea, oral mucosa, and the peripheral nerve, with several fibrin-agarose advanced therapy medicinal products (ATMP) already reaching clinical application, including the skin substitute UGRSKIN, the artificial cornea NANOULCOR and the palate mucosa BIOCLEFT. Together, current evidence positions agarose as a versatile and translationally relevant biomaterial for next-generation TE, warranting further exploration of its potential in additional therapeutic contexts. Full article

N-acetylcysteine (NAC) is a synthetic derivative of L-cysteine, known since the mid-20th century as a mucolytic agent and, in recent decades, has attracted attention for its antioxidant and antibiofilm properties. Bacterial biofilms are structured communities of microorganisms enclosed in an extracellular polymeric matrix, which accounts for their markedly increased resistance to antibiotics (up to 1000-fold higher than in planktonic forms) and to the host immune response. According to the literature, up to 65% of infectious agents are associated with biofilm formation, making them a challenging therapeutic target. This review systematizes current data on the molecular mechanisms of the antibiofilm action of NAC, including disruption of matrix proteins and polysaccharides, degradation of extracellular DNA, suppression of the quorum sensing system, and disturbance of bacterial redox homeostasis. Particular attention is given to synergistic combinations of NAC with antibiotics of five major classes; effective concentrations are provided, and the types of interaction are characterized. The results of clinical studies from the last decade are reviewed, demonstrating the potential of NAC as an adjuvant in urinary tract infections, chronic rhinosinusitis, diabetic osteomyelitis, and cystic fibrosis. The main limitations (pH dependence, instability, low oral bioavailability) are critically evaluated, and approaches to overcoming them using nanoparticles, hydrogels, and combinations with propolis or chitosan are proposed. The review is intended for researchers in antimicrobial chemotherapy and developers of new drug delivery systems. Full article

Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a thermosensitive chitosan (CS)–sea cucumber peptide (SCP) hydrogel (CS–SCP gel) loaded with SCP using NaHCO₃ as a crosslinker and characterized its properties. Kunming mouse models of anti-intoxication and acute alcohol-induced liver and brain injuries were established. The anti-intoxication and organ-protective effects of the CS–SCP gel were comprehensively evaluated through behavioral observation, liver histopathology, and biochemical assays of serum and liver, kidney, and brain tissues. The CS–SCP gel exhibited a phase transition temperature of 35.7 °C, a water absorption rate of 1015.47%, and a cumulative peptide release of 74.83% within 330 min. In mice, it prolonged the latency to drunkenness; shortened alcohol-induced sleep and sobering time; reduced blood ethanol, transaminase, and lipid levels; upregulated hepatic antioxidant enzymes; downregulated pro-inflammatory cytokines, and alleviated lipid peroxidation. It also enhanced brain antioxidant capacity, suppressed cerebral inflammatory cytokines, and maintained cholinergic neurotransmitter homeostasis. Collectively, with sustained release, CS–SCP gel is expected to prolong the pharmacological action of SCP, enhance therapeutic efficacy, and protect against alcohol-induced liver and brain injury through the regulation of oxidative stress and attenuation of inflammation. Full article

Background/Objectives: Renal ischemia–reperfusion injury (IRI) and infection-associated renal damage are characterized by persistent inflammation, oxidative stress, microvascular dysfunction, and impaired tissue regeneration, creating a hostile microenvironment that limits effective repair. We developed an injectable, photocrosslinkable methacrylated chitosan (CSMA) hydrogel for the localized co-delivery of cerium oxide nanoparticles (CeO₂NPs) and vascular endothelial growth factor (VEGF), aiming to integrate redox modulation, antibacterial activity, and regenerative support. Methods: Gelation, microstructure, rheology, degradation, and CeO2NP/VEGF were characterized. Tubular epithelial and fibroblast migration and endothelial network formation, angiogenic gene expression, and antibacterial activity against Staphylococcus aureus and Escherichia coli were evaluated in vitro. Theraputic performance was assessed by renal surface application in a rat renal IRI model and catheter-mediated interavsical administration in an ascending urinary tract infection model. Systematic biocompatibility was evaluated separately in a 14-day subcutaneous implantation study. Renal response were further investigated using transcriptomic and targeted molecular analyses. Results: The CSMA/VEGF/CeO₂NPs hydrogel exhibited rapid in situ gelation, interconnected porous architecture, stable viscoelasticity, gradual degradation, and sustained release of both CeO₂NPs and VEGF. The formulation enhanced tubular epithelial and fibroblast migration, promoted endothelial network formation and angiogenic gene expression and effectively inhibited both S. aureus and E. coli. In a surgically controlled rat renal IRI model, direct renal-surface application of the hydrogel reduced tubular injury, inflammatory infiltration, and fibrotic remodeling. In a separate ascending urinary tract infection model, catheter-based intravesical administration reduced the ascending renal bacterial burden and infection-associated inflammatory injury. No detectable adverse systemic effects observed under the tested conditions over the 14-day observation period in the subcutaneous implantation. Transcriptomic analyses further revealed that CSMA/VEGF/CeO₂NPs treatment was associated with marked remodeling of the renal injury microenvironment, characterized by suppression of antigen presentation and immune activation pathways, alongside restoration of metabolic programs associated with amino acid, lipid, and purine metabolism. These molecular changes were accompanied by downregulation of CIITA/CD74/MHC-II signaling, recovery of metabolic regulators AGXT and ACOX1, modulation of Hippo/YAP- and ECM-associated pathways, and preservation of renal structural markers including nephrin and WT1. Conclusions: The localized CSMA-mediated co-delivery of CSMA/VEGF/CeO₂NPs hydrogel promotes renal repair through resolution of maladaptive immune activation, metabolic reprogramming, angiogenic enhancement, and preservation of renal structural integrity, providing a promising biomaterial strategy for the treatment of ischemic and infection-associated renal injuries. Full article

Azithromycin is widely used in dentistry as a systemic antibiotic, particularly for odontogenic infections and as an alternative in patients with β-lactam hypersensitivity. Beyond its antimicrobial activity, azithromycin possesses unique pharmacokinetic, anti-inflammatory, immunomodulatory, and anti-biofilm properties. Together with growing concerns regarding antimicrobial resistance and antibiotic stewardship, these characteristics have stimulated interest in local drug-delivery strategies that may reduce systemic antibiotic exposure while maintaining therapeutic efficacy. This narrative review evaluates the rationale, potential clinical applications, and current evidence supporting local azithromycin delivery in dentistry. The available literature on azithromycin pharmacology, systemic dental use, immunomodulatory mechanisms, biofilm-related effects, local drug-delivery systems, safety, and regulatory considerations was critically reviewed. Current evidence suggests that locally delivered azithromycin may achieve high drug concentrations at the target site, enhance anti-biofilm activity, modulate local inflammation, and minimize systemic exposure. Potential applications include periodontitis, peri-implant diseases, persistent endodontic infections, oral surgery, and regenerative procedures such as bone augmentation and maxillary sinus floor elevation. Emerging delivery platforms, such as hydrogels, thermoresponsive gels, nanoparticles, and chitosan-based systems, further support the feasibility of this approach. Experimental findings also indicate that azithromycin may inhibit osteoclast activity, suggesting additional benefits for bone preservation and regenerative healing. Despite these promising findings, current evidence remains limited and is derived mainly from preclinical studies and small clinical investigations. Further translational research and well-designed randomized controlled trials are needed to establish the safety, efficacy, and optimal clinical role of locally delivered azithromycin in evidence-based dental practice. Full article

(1) Background: Impaired diabetic wound healing stems from systemic dysregulation of the wound-healing cascade under hyperglycemic conditions, producing a disordered microenvironment marked by sustained inflammation, defective angiogenesis, and aberrant extracellular matrix remodeling, multifactorial, multistage pathological interactions demanding multi-target intervention. (2) Methods: We constructed a multifunctional nanocomposite hydrogel dressing (PGAs@CDV) based on a “drug-carrier integration” strategy, targeting the dysregulated hemostasis, inflammation, and proliferation phases of diabetic wound healing. An amphiphilic micelle carrier (PNO-GA) was synthesized by covalently conjugating Panax notoginseng oligosaccharide with gallic acid, loaded with Anemoside B4 to yield drug-loaded nanomicelles (PGAs), embedded into a carboxymethyl chitosan-dopamine-vanillin hydrogel (CDV) matrix to form PGAs@CDV. We then examined how PGAs@CDV affected diabetic wound healing. (3) Results: In vitro, PGAs@CDV enhanced cell migration and angiogenic capacity, exhibited potent antioxidant activity, and promoted M1-to-M2 macrophage polarization. We tested PGAs@CDV in a streptozotocin-induced diabetic mouse wound model. Wounds treated with PGAs@CDV closed faster than those treated with the control, CDV, PNO@CDV, and AB4@CDV. Four readouts tracked this difference: hemostasis was quicker, inflammation was lower, more blood vessels formed, and collagen deposition was higher. At the pathway level, PGAs@CDV suppressed NF-κB signaling and activated PI3K/AKT/HIF-1α. These two arms map onto the anti-inflammatory and pro-angiogenic effects observed above. (4) Conclusions: This nanocomposite hydrogel integrates a bioactive carrier with a therapeutic payload to enable coordinated intervention across multiple phases of diabetic wound repair. By combining structural support with sustained pharmacological activity, it offers a promising strategy for the treatment of chronic diabetic wounds. Full article