The presence of bacterial drug resistance and biofilms significantly hinders the healing of bacteria-infected wounds by reducing the effectiveness of antibiotics and maintaining inflammatory reactions. To address this issue, a multifunctional hydrogel (HXM) that combines photothermal therapy (PTT), photodynamic therapy (PDT), and enzyme-like activity is fabricated in this study. The HXM hydrogel is synthesized via a thiol-ene click reaction between 4-ARM-PEG5000-SH and hyaluronic acid (HA) modified with organic small molecule dyes (cyanine dyes (Cy5.5(COOH))) and methacrylic anhydride (MA) (HA-Cy5.5(COOH)-MA), followed by MoS2 coordination. Under near-infrared irradiation, the hydrogel exerts potent antibacterial effects via synergistic PTT/PDT. After infection control, the hydrogel promotes the polarization of macrophages to the M2 type, upregulating antioxidant enzymes (superoxide dismutase-like) to scavenge excess reactive oxygen species (ROS). Meanwhile, it secretes anti-inflammatory cytokine interleukin-10, which helps resolve inflammation and accelerate infected wound repair. Further, its intrinsic catalase-like activity degrades ROS, disrupting the ROS cycle. In vivo, the HXM hydrogel exhibited antibacterial, antioxidant, and anti-inflammatory functions, enhancing wound closure through coordinated biofilm disruption and oxidative stress mitigation. Therefore, this work is expected to provide a potential therapeutic strategy for promoting infected wound healing in vivo.

Reprogramming endothelial tip cell fate via PI3K-VEGF signaling cascade: a multifunctional adhesive hydrogel for enhanced angiogenesis and infected wound healing

Traditional hyperthermia-boosted photothermal therapy (PTT) for infected wounds often suffers from thermal damage to healthy tissue, exacerbates immune dysregulation, and compromises antibacterial efficacy in deep tissue. Here, we developed a functional microneedle system (MTF@MNs) by incorporating MXene-tannic acid/iron (MXene-TA/Fe, MTF) nanosheets into a photocrosslinkable GelMA/PEGDA hydrogel matrix. The engineered microneedle architecture facilitates targeted delivery of therapeutic nanosheets into deep, biofilm-rich subcutaneous regions, which are characterized by elevated H2O2 levels, acidic pH, and poor drug permeability. Under mild near-infrared (NIR) irradiation, MTF@MNs synergistically enhance the peroxidase-like nanozyme activity of MXene-TA/Fe while accelerating Fe2+/Fe3+ release, facilitating efficient eradication of deep-tissue infections without thermal injury. Our results demonstrate that MTF@MNs not only exhibit robust reactive oxygen species (ROS) scavenging capacity, but also promote macrophage polarization toward pro-regenerative phenotypes. Furthermore, they attenuate pro-inflammatory cytokine release by inhibiting the TNF/MAPK signaling pathway in macrophages. Collectively, the MTF@MNs system accelerates infected wound healing through reprogramming the immune microenvironment, enhancing collagen deposition, and stimulating angiogenesis, thus offering a promising strategy for the management of deep-tissue infections.

Recently, electrospun nanofiber composite scaffolds encaged with bioactive agents have gained prominence as an innovative therapy for managing full-thickness infectious wounds. This study mainly focuses on the development and comprehensive characterization of multi-component polyvinyl alcohol (PVA)-based nanofiber scaffolds incorporating pupae oil (PO) and Prussian blue nanoparticles (PBNPs) using electrospinning technique for accelerated full thickness infectious wound healing. Scanning electron microscopy (SEM)photographs revealed a porous, interconnected fibrous structure with diameters ranging between 200 and 300nm. Fourier-transform infrared spectroscopy confirmed the chemical compatibility and successful incorporation of PO and PBNPs into the scaffolds. The scaffolds exhibited optimal biodegradation over a two-week period and demonstrated appropriate water uptake capacity to absorb wound exudates. Furthermore, they displayed potent antibacterial and antibiofilm efficacy against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), as well as minimal microbial penetration across nanofiber scaffolds. In vitro studies on L-929 fibroblast cells indicated improved cell viability, migration, cell adhesion, and proliferation. In vivo evaluation in an infected rat model demonstrated rapid wound closure and improved tissue regeneration. Moreover, haematoxylin and eosin (H&E) and masson-trichome staining corroborated the scaffolds' excellent wound healing efficacy. Additionally, enzyme-linked immunosorbent assay demonstrated significant downregulation of key pro-inflammatory markers. These results suggest that the bioinspired, multi-component PVA-based nanofiber scaffolds loaded with natural bioactive agents (PO and PBNPs), hold great potential as a therapeutic strategy for promoting enhanced healing of full-thickness infected wounds.

Metal polyphenol double-network hydrogels based on chitosan/hyaluronic acid loaded with rosmarinic acid promote the healing and repair of infected wounds.

Retraction notice to "Multifunctional chondroitin sulfate based hydrogels for promoting infected diabetic wounds healing by chemo-photothermal antibacterial and cytokine modulation" [Carbohydrate Polymers 314 (2023) 120937

Highly adhesive, stretch, antioxidative and antibacterial double-network hydrogel containing artemisinin for infected wound closure and healing

Retraction notice to "A bioactive dextran-based hydrogel promote the healing of infected wounds via antibacterial and immunomodulatory" [Carbohydrate Polymers 291 (2022) 119558

Apoptotic extracellular vesicles derived from mesenchymal stromal cells encapsulated in chitosan-modified hydrogels with multiple and sequential regulatory functions for infected wound healing

Multifunctional protein-polysaccharide hydrogel with antimicrobial and angiogenic properties to promote infected wound healing.

Porous chitin powder decorated with ZIF-8-derived nanozyme for diabetic infected wound healing.

A multifunctional fungal defensin bladesin loaded-hydrogel for accelerated infectious wound healing

Dextran based hydrogel wound dressing with cytocompatible, anti-protein and antibacterial properties for infected wound healing.

Chitosan-based double-network hydrogel with synergistic photothermal/nitric oxide therapy for methicillin-resistance Staphylococcus aureus infected wound healing.

Bioactive binary Schiff-base hydrogel from chitosan and functional PEGylated dialdehydes: Synthesis and structure-properties correlation.

Biofilms, formed by microorganisms and surrounding substances, hinder traditional drug delivery and delay wound healing. Microneedles, with their excellent mechanical properties, minimally invasive nature, and ability to penetrate biofilms for rapid drug delivery, offer a promising solution for biofilm eradication. In this study, we developed an intelligent, responsive bilayer microneedle system (CurMN@RRH) based on photodynamic therapy to accelerate wound healing caused by bacterial infections. Cur@ZIF-8 nanoparticles are synthesized in a one-pot process and embedded in gelatin and hyaluronic acid to form the microneedle tips. The microneedle substrate consists of ROS-responsive boronate-ester-based hydrogels (TSPBA-PVA), loaded with the antioxidant glutathione (GSH). In the early stages of wound healing, the acidic environment triggered by bacterial infection prompts the release of curcumin from Cur@ZIF-8 nanoparticles, which generates hydroxyl radicals under blue light to promote bacterial death. In later stages, the CurMN@RRH microneedles release GSH, clearing excessive reactive oxygen species and reducing inflammation, thus accelerating healing. Both in vitro and in vivo experiments demonstrate that the intelligent CurMN@RRH microneedles exhibited strong antibacterial, anti-inflammatory, and antioxidant properties, promoted cell proliferation, and accelerated tissue wound healing. This approach offers a novel strategy for treating bacterial infection-induced wounds.

Background/Objectives: Natural plant-based compounds, especially black pepper extract, are known to have anti-inflammatory, antibacterial, and antioxidant qualities that promote procollagen formation and wound healing. This study focused on developing a collagen-based composite enriched with P. nigrum extract in powder form, designed to enhance the efficacy of the antibiotic cefazolin while promoting the healing of chronic wounds. Methods: The polyphenolic P. nigrum extract was obtained by ultrasound-assisted extraction and was characterised by UHPLC-MS/MS and spectrophotometry. Antimicrobial and antioxidant activities were assessed using conventional methods. Pharmacokinetic and pharmacodynamic parameters were evaluated for the specific taxon compounds using Deep-RK. P. nigrum extract was incorporated into a collagen hydrogel with arginine and freeze-dried. The powders were characterised by FTIR, SEM, TGA-DSC, and DLS. The antimicrobial activity and potential synergistic effects with cefazolin were evaluated on reference microbial strains and isolates from infected wounds. Biocompatibility and hemocompatibility were evaluated, as well as wound closure in vitro. Results: Polyphenols, including phenolic acids, stilbenes, anthocyanins, and flavonoids, which provide a potent antioxidant capacity through electron transfer mechanisms (FRAP, CUPRAC), were abundant in the P. nigrum extract. FTIR and SEM analyses confirmed the integration of phenolic compounds into the collagen–arginine matrix without protein denaturation. TGA–DSC data showed thermal stabilisation at moderate extract concentrations. The extract exhibited predominantly bacteriostatic antibacterial activity and antibiofilm effects, with synergy/additivity with cefazolin, especially at medium doses. Tests on keratinocytes confirmed biocompatibility, and hemocompatibility demonstrated an excellent safety profile, with protection against AAPH-induced oxidative stress. Conclusions: Overall, collagen powders with P. nigrum extract at moderate/low concentrations combine stability, antibiotic-enhanced activity, and cellular compatibility, making them promising adjuvants for the topical treatment of chronically infected wounds.

ABSTRACTHydrogel microparticles with different actives encapsulation have reliable efficacy in wound repair, and the challenge is to improve the active substance to improve the efficacy. Here, a novel ultrasonic responsive core‐shell microcapsule delivery system is proposed, which can simultaneously load traditional Chinese medicine sonosensitizer and oxygen synergistic effect to promote the healing of infected wounds. The microcapsule has a core of oxygen‐rich perfluorocarbon (PO) and a hydrogel shell with curcumin (PO/C‐MC). Ultrasound can trigger the release of oxygen from perfluorocarbon and stimulate the sonodynamic effect of curcumin, which is not only an anti‐inflammatory traditional Chinese medicine but also a sonosensitizer, thus realizing the synergistic treatment of traditional Chinese medicine and acoustic dynamics. Under the irradiation of low‐intensity ultrasound, PO/C‐MCs can effectively increase the oxygen concentration and enhance the antibacterial effect of sonodynamic therapy, synergizing with the anti‐inflammatory effect of traditional Chinese medicine to promote the rapid healing of chronic infected wounds. The study demonstrated that ultrasound‐responsive PO/C‐MCs microcapsules significantly enhanced the healing process of infected wounds in mice. Given these beneficial characteristics, PO/C‐MCs represent a promising therapeutic candidate with considerable potential for clinical application in managing chronic infected wounds.

Infected wounds suffer from limited self-healing, persistent bacterial infections, prolonged inflammation, and oxidative wound microenvironment. While anti-bacterial peptides such as SAAP148 demonstrate remarkable efficacy against drug-resistant pathogens, their clinical application is hindered by rapid inactivation and uncontrolled burst release. To address these limitations, collagen type I (Col I) is integrated with self-assembling peptide RADA16 to develop a novel self-assembled nano-micro structured hydrogel (Col I-RADA16, CR) without chemical cross-linkers. This unique design leverages the micron-scale porous structure of Col I and the nanofibrous architecture of RADA16, resulting in a hydrogel with excellent mechanical properties, sustained SAAP148 release, and enhanced bioactivity. CR not only promotes fibroblast adhesion, migration, and proliferation, but when loaded with SAAP148 (Col I-RADA16-SAAP148, CRS), effectively inhibits bacterial infection, enhances macrophage polarization and accelerates wound healing in vivo. Importantly, histological and immunohistochemical analyses revealed that the CRS hydrogel significantly enhances regeneration of skin appendages (e.g., hair follicles and glands) by action of CK5 and CK14 in the ERBB/MAPK, mTOR/PI3K-Akt, JNK/p38 MAPK signaling axes, significantly surpassing the performance of traditional collagen or gelatin sponges. This innovative dual-scale design and cross-linker-free fabrication strategy offers a versatile and clinically translatable platform for infected wound healing, addressing critical limitations in current wound care technologies.

To evaluate the clinical efficacy of metronidazole topical solution in preventing surgical site infections and promoting wound healing. A comprehensive literature review was conducted using PubMed, EMBASE, Cochrane Database, and China National Knowledge Base to evaluate the impact of metronidazole topical (MS) and physiological saline rinses (SS) on infection rates and wound healing in patients with septic appendicitis after treatment. Review Manager 5.0 was utilized to evaluate the outcomes of the selected studies. The impact of the selected articles was assessed through Forest plot analysis, sensitivity analysis, and bias analysis conducted on the gathered data. Eight studies met the inclusion criteria. The results showed a significantly lower surgical site infection rate in the metronidazole (MS) group compared to the saline (SS) group (RR = 0.28, 100% CI [0.15, 0.51], P = 0.05, I ²= 59%). However, no significant difference was observed in grade I healing rates between the two groups (RR = 1.02, 100% CI [0.91, 1.15], P = 0.41, I ² = 0%). Similarly, there was a significant difference in grade II healing rates ((RR = 0.7, 100% CI [0.32, 1.55], P = 0.30, I² =5%). A significant heterogeneity was observed in grade III healing rates (RR = 0.56, 100% CI [0.17, 1.89], P = 0.21, I² =36%). Sensitivity analysis and funnel plots showed that the study was credible with limited publication bias. Metronidazole topical rinse may be more effective and safer than saline rinse in treating purulent appendicitis. Local application of metronidazole to purulent appendicitis incisions is a promising approach. The review was not registered prospectively and some included studies had moderate bias. Larger multicenter trials are needed to validate the efficacy of metronidazole irrigation across diverse patient populations.