Bioactive granular hydrogels for infection control and immune microenvironment remodeling in wound regeneration

From Infection Control to Tissue Regeneration: Mechanisms, Design Strategies, and Smart Advances in Antibacterial Hydrogels

Bacterial infection, biofilm formation, and the associated oxidative stress and persistent inflammation represent major obstacles to wound healing, tissue engineering, and implantable medical devices. Owing to their highly hydrated three-dimensional networks, favorable tissue compatibility, and versatile capacity for functional loading, hydrogels have been widely investigated for the treatment of infected wounds. This review systematically summarizes the major antibacterial mechanisms of hydrogels, including cationic contact-killing, chemical antibacterial activity mediated by metal ions and reactive halogen species, nanozyme-catalyzed reactions and bidirectional regulation of reactive oxygen species, as well as photothermal synergistic antibacterial therapy. Key design strategies are also discussed, including natural polymer-based matrices, multiple dynamic crosslinking, stimuli-responsive controlled release, three-dimensional printing, and spatial compartmentalization. In addition, recent advances in infection-microenvironment regulation, wet-interface adaptation, temporally coordinated tissue repair, and integrated diagnosis and therapy are highlighted. The field is currently shifting from single-mode bacterial eradication toward multistage tissue repair and intelligent theranostics. However, major challenges remain, including balancing antibacterial efficacy with biosafety, achieving reproducible manufacturing and sterilization-compatible formulations, maintaining functional stability during storage, and improving the clinical relevance and standardization of preclinical evaluation. In addition, most smart systems still lack quantitative coupling among pathological signals, therapeutic dosage, and treatment outcomes. Future studies should therefore integrate mechanistic design with manufacturing reproducibility, clinically relevant validation, and quantitative feedback regulation, thereby advancing antibacterial hydrogels from multifunctional proof-of-concept systems toward precise, controllable, and clinically translatable therapeutic platforms.

Peptide-Zinc Nanoflower Hydrogel for Diabetic Wound Healing

Refractory diabetic wounds are chronic healing disorders characterized by a complex pathological microenvironment involving excessive oxidative stress, persistent inflammation, bacterial infection, and impaired angiogenesis. Existing functional nanobiomaterials often exhibit rapid release and limited therapeutic functionality, resulting in insufficient retention at wound sites and inadequate regulation of the different stages of wound healing. To address these limitations, we developed a composite hydrogel incorporating organic-inorganic peptide-zinc nanoflowers for sustained local delivery. The nanoflowers were formed through the co-assembly of Zn²⁺ with azide-functionalized FP2 (N₃-ERGVVSIKGV) and subsequently covalently immobilized within a click-crosslinked hyaluronic acid network via strain-promoted azide-alkyne cycloaddition. The hierarchical nanoflower architecture, covalent immobilization, and hydrogel network confinement collectively prolonged local retention and enabled sustained release of the bioactive components. The resulting hydrogel regulated the diabetic wound microenvironment through antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic activities, thereby promoting tissue regeneration and accelerating wound closure. These findings demonstrate a multifunctional sustained-delivery strategy for the treatment of complex diabetic wounds.

pH-Responsive Multinetwork Hydrogel with Antibacterial, Anti-Inflammatory, and Microenvironment-Modulating Properties for Enhanced Hemostasis and Wound Healing.

A multifunctional hydrogel with antibacterial, antioxidant, and anti-inflammatory properties for accelerated wound healing is presented.

Polysaccharide based biomaterials for advanced wound healing applications

Healing a wound is a complex biological process involving hemostasis, inflammation, cell proliferation, and tissue remodeling. Ad interim, polysaccharide based biomaterials have also attracted significant attention in wound healing due to their intrinsic biocompatibility, biodegradability and structural versatility, and ability to actively modulate the wound microenvironment. This review focuses on key polysaccharides, including alginate, chitosan and hyaluronic acid and discusses their roles across different stages of wound healing by correlating material structure with biological performance. The relationship between material structure and biological performance is discussed to understand their therapeutic effects. Recent advances in hybrid biomaterials, ion-coordination strategies, and stimuli-responsive dressings are highlighted for their roles in enhancing antimicrobial activity, promoting angiogenesis, and enabling controlled therapeutic delivery. Special emphasis is also placed on the emerging role of polysaccharide-based biomaterials in combating chronic wound-associated biofilms through disruption of the extracellular polymeric substance matrix, modulation of quorum-sensing pathways, and localized antimicrobial delivery. These multifunctional approaches improve infection control while simultaneously supporting tissue regeneration, thereby addressing one of the principal challenges associated with chronic wound management. The purpose of this review is to look at the impact of the use of these materials on the environment, specifically by looking at both their biodegradability and lessening of our dependency on synthetic polymers, as well as presenting an integrated design framework that links the composition, physicochemical characteristics, and biological demands of biomaterials within a time-based context to provide a rational approach for developing future wound dressings. Despite promising progress, challenges related to reproducibility, scalability, and clinical translation remain significant, underscoring the need for standardized evaluation and interdisciplinary approaches.

Spatiotemporally programmed core-shell multilayer hydrogel spheres dressing for scarless infected wound healing.

MBene-Empowered Multifunctional Sprayable Hydrogel for Burn Wound Treatment.

Burn wounds are challenging to heal due to irregular tissue architecture, high bacterial susceptibility, excessive oxidative stress, and prolonged inflammation. Here, we report a multifunctional sprayable hydrogel (PM) by integrating MoB (MBene) nanosheets into a thermoresponsive Pluronic F127 matrix for comprehensive burn wound therapy. Benefiting from electron-deficient boron sites and multivalent Mo states, MoB exhibits robust SOD- and CAT-mimetic activities, enabling efficient ROS scavenging, restoration of mitochondrial homeostasis, and macrophage polarization toward an anti-inflammatory M2 phenotype. Meanwhile, MoB shows high photothermal conversion efficiency, endowing the hydrogel with potent photothermal antibacterial activity, achieving >90% bacterial inhibition. In vivo studies demonstrate that PM hydrogel combined with light irradiation effectively remodels the wound microenvironment and markedly accelerates healing of infected burn wounds, reaching a 94% healing rate by day 14. Transcriptomic analyses further reveal that PM promotes tissue repair by modulating immune responses, enhancing cell migration and differentiation, and activating wound-regeneration-related pathways. Overall, this MoB-empowered sprayable hydrogel represents a promising, translatable platform integrating antioxidative, immunomodulatory, and antibacterial functions for effective management of infected burn wounds.