年度核心文献汇总

Diabetic wounds are sustained by persistent inflammation, impaired angiogenesis, abnormal extracellular matrix (ECM) remodeling, and delayed re-epithelialization. Adipose-derived stem cell exosomes (ADSC-Exos) offer a cell-free strategy because their multicomponent cargo can modulate immune responses, vascular regeneration, fibroblast activity, and epidermal repair. Mechanistic studies suggest that ADSC-Exos promote macrophage immunometabolic reprogramming, restore pro-angiogenic signaling, improve matrix homeostasis, and protect keratinocytes from oxidative injury. Engineering approaches and biomaterial-based delivery systems may further improve local retention, controlled release, and therapeutic activity. Distinct from existing ADSC-Exos reviews, this review adopts a pathology-to-translation framework that connects the major pathological features of diabetic wounds with ADSC-Exos mechanisms, engineering strategies, delivery optimization, and clinical translation. Particular emphasis is placed on donor- and process-dependent heterogeneity, potency assessment, GMP-compatible manufacturing, biodistribution, long-term safety, and regulation. Overall, ADSC-Exos represent a mechanistically compelling preclinical platform, but clinical translation will require reproducible product quality, standardized potency criteria, scalable manufacturing, and rigorous clinical validation.

Objective Dysregulation of M1/M2 macrophage polarization drives sepsis and impaired wound healing. Deubiquitinases (DUBs) are promisingdrug targets, but the role of ubiquitin-specific protease 47 (USP47) in macrophage plasticity remains unclear. This study investigated the regulatoryfunction of USP47 in macrophage polarization and its therapeutic potential for inflammatory disorders. Methods In vitro, human THP-1 and mouse bonemarrow-derived macrophages were polarized, with USP47 modulated via genetic manipulation or the inhibitor P22077. In vivo, LPS-induced septicperitonitis and cutaneous wound models were used to evaluate the effects of Usp47 deficiency or P22077 treatment. Mechanistically, protein interactionand ubiquitination assays were performed to verify the USP47-YAP axis and downstream signaling. Results USP47 was upregulated in M1 macrophagesand downregulated in M2 macrophages. USP47 inhibition skewed macrophages toward the M2 phenotype. In vivo , Usp47 knockout or P22077 treatmentimproved survival in septic mice, reduced systemic inflammation, and accelerated wound healing, accompanied by increased M2 infiltration at lesion sites.Mechanistically, USP47 directly deubiquitinated and stabilized YAP protein; stabilized YAP drove M1 polarization via two parallel axes: nucleartranslocation to promote pro-inflammatory cytokine transcription, and promotion of NLRP3 inflammasome stabilization. Conclusions USP47 is a critical regulator of macrophage polarization via the USP47-YAP-NLRP3 axis. Targeting USP47 exerts anti-inflammatory and pro-repair effects, representing a promising therapeutic strategy for sepsis and wound healing disorders.

Background Skin homeostasis, protection against ultraviolet radiation (UVR), and wound repair depend on coordinated interactions among melanocytes, keratinocytes, and fibroblasts. Horizontal mitochondrial transfer (HMT) is a naturally occurring form of intercellular communication in which mitochondria move between cells and may contribute to stress adaptation, cellular recovery, and tissue resilience. Artificial mitochondrial transfer (AMT), performed in vitro or ex vivo, and mitochondrial transplantation (MT), involving the direct administration of isolated mitochondria in vivo, seek to therapeutically harness these biological mechanisms. However, HMT among resident skin cells and its relationship to mitochondria-based regenerative strategies remain poorly understood. Methods HMT among human melanocytes, keratinocytes, and fibroblasts was evaluated under basal conditions and following UVR exposure. Direct 2D coculture and transwell systems were used to assess predominantly contact-dependent and contact-independent HMT, respectively, using fluorescence microscopy. AMT was performed by delivering isolated mitochondria from human fibroblast, human Wharton's jellymesenchymal stem/stromal cells (WJ-MSCs), or mouse bone marrow MSCs (BM-MSCs) to recipient fibroblasts, followed by assessment of mitochondrial uptake, reactive oxygen species (ROS) production, and cell proliferation. The regenerative effects of locally administered MSC-derived mitochondria were subsequently evaluated in murine and porcine primary-intention wound models: mouse BM-MSC-derived mitochondria were used in murine wounds, whereas human WJ-MSC-derived mitochondria were used in porcine wounds. Outcomes were assessed using histological analysis, the wound healing index (WHI), and, in pigs, spatial quantification of Ki67-positive cells. Results HMT from melanocytes to keratinocytes increased significantly after UVR exposure and occurred predominantly under direct coculture conditions, reaching approximat

Bacterial infections significantly impede wound healing and threaten global public health. Although photodynamic therapy (PDT) has emerged as a promising antibiotic-free antibacterial strategy, the hypoxic condition within biofilms has limited the clinical effectiveness of conventional oxygen-dependent PDT. Herein, we designed and prepared a novel type I/II dual-mechanism and oxygen-independent aryl free radical combined oxime ester based photoinitiator (DPTO) for treating bacterial infections and enhancing wound healing. Upon white light irradiation, DPTO generates type I and type II ROS ( 1 O₂, O₂• - , and •OH) via photodynamic process. Additionally, DPTO undergoes photolysis to produce oxygen-independent aryl free radical. Particularly, DPTO could accumulate in the mitochondria, boost mitochondrial radicals, and damage mitochondria. The combined generation of type-I/II ROS and aryl free radicals confers potent in vitro antibacterial activity. Crucially, significant in vivo therapeutic efficacy was validated in a rat wound infection model. In summary, our study not only validates the substantial potential of DPTO in photodynamic antibacterial therapy but also provides a foundation for developing efficient oxime ester based photoinitiator for the treatment of bacterial infections.

Objective: Early case series using a synthetic bilayer biodegradable matrix (BTM) for diabetes-related neuropathic and neuroischemic foot wounds have shown encouraging outcomes. This study reports results from a single-centre randomised controlled trial evaluating its efficacy in a diabetes-related foot wound cohort. Methods: Participants with moderate-to-severe post-surgical diabetes-related foot wounds (Society of Vascular Surgery WIfI grade 3 or 4) were randomised to BTM plus usual standard of care (USOC) or USOC alone. Primary outcomes were complete wound healing and amputation rates at 12 months; secondary outcomes included time to healing, wound surface area reduction, and infection rates. (Ethics approval 2021/HRE00214, ACTRNNo. 12621001613897). Results: Between May 2022 and September 2024, 64 participants were enrolled (31 BTM + USOC, 30 USOC alone; three did not complete treatment). At 12 months, complete healing occurred in 64.5% of BTM-treated wounds versus 56.7% of USOC wounds ( p = 0.53, non-significant), with no significant difference in amputation rates. Post hoc Kaplan-Meier analysis of wounds with a starting surface area greater than 10 cm 2 showed significantly faster healing in the BTM group (median 219 days) versus USOC alone (312 days, log-rank p = 0.037). A multivariate Cox proportional hazards regression, adjusting for WIfI score, age and starting wound area, confirmed this effect (HR 2.67, 95% CI 1.04-6.86, p = 0.04), with large BTM-treated wounds healed approximately 2.7 times faster than USOC alone. Conclusions: In this exploratory, post hoc analysis, BTM was associated with a reduction in time to complete healing in large post-surgical diabetes-related foot wounds compared with USOC. Given the post hoc nature of this finding, confirmation in a prospectively powered trial is warranted.

Chronic wounds represent a global healthcare challenge, characterized by persistent inflammation, microbial infection, and compromised tissue regeneration, often refractory to conventional therapies. Natural phytochemicals, with their inherent diverse bioactivities, provide a multi-target approach to modulate inflammation and accelerate tissue repair, overcoming the limitations of single-agent interventions. However, their clinical utility is frequently limited by poor physicochemical stability, low bioavailability, and insufficient retention at the wound site. Advanced hydrogel platforms serve as effective delivery systems, capable of encapsulating these potent compounds to ensure localized, sustained, and on-demand release, addressing critical translational barriers. This review examines the wound-healing mechanisms and molecular targets of key phytochemical classes, critically analyzing their physicochemical limitations. We then discuss the rational design principles of phytochemical hydrogel systems, encompassing stimuli-responsive networks, externally triggered release modalities, and 3D-printed scaffolds for precise spatial drug distribution. We also highlight the emerging role of artificial intelligence in accelerating this field, from predicting hydrogel characteristics and screening novel phytochemicals to optimizing formulation strategies. Finally, we propose a strategic translational roadmap, addressing crucial aspects such as botanical standardization, scalable manufacturing, and regulatory pathways, to support the clinical translation of these systems.

Nitric oxide's (NO) crucial role in various physiological processes, such as vascular regulation, inflammation, and wound healing, has led to the development of various NO delivery platforms. However, delivering NO in a controlled and sustained manner is challenging due to its short half-life of less than 5 s. To address this challenge, we synthesized polyacrylamide (PAAm) hydrogels loaded with selenium nanoparticles (SeNPs) or polydopamine-coated selenium nanoparticles (Se@PDA NPs), which can catalytically generate NO from both endogenous and exogenous NO donors. Structural characterization confirmed that nanoparticle loading did not alter the intrinsic properties of the PAAm-gel. By adjusting the concentration of NPs loaded within the hydrogels, tunable NO generation was achieved. Both Se-gel and Se@PDA-gel exhibited sustained NO generation, with Se@PDA-gel demonstrating superior recyclability and stability, even after long-term storage under various conditions. The hydrogels exhibited excellent biocompatibility, and their biological activity was validated by elevated interleukin-10 (IL-10) and α-smooth muscle actin (α-SMA) expression, indicating anti-inflammatory effects and potential for wound healing, respectively. These findings establish Se@PDA-gel as a promising platform for controlled and sustained NO delivery, offering therapeutic potential in wound healing and anti-inflammatory therapies, particularly for cardiovascular and infectious diseases.

Background/Objectives : Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is intended to restore reparative signaling in diabetic wounds, yet its efficacy and the contribution of delivery systems remain uncertain. This systematic review evaluated its preclinical efficacy, mechanistic responses, safety, risk of bias, certainty, and attribution of effects. Methods : Following PRISMA 2020 and an OSF-registered protocol, PubMed, Embase, Scopus, Web of Science, and ScienceDirect were searched from inception to 29 July 2026 for controlled in vivo diabetic wound studies. Compatible outcomes were pooled using random-effects models with restricted maximum-likelihood estimation and Hartung-Knapp adjustment. Non-poolable findings were synthesized using attribution-specific effect direction maps. Risk of bias and certainty were assessed with SYRCLE and preclinical GRADE, respectively. Results : Twenty-nine studies were included from 3844 records. For percentage wound closure at days 10-12, three studies comprising 113 animals yielded a favorable but imprecise pooled estimate (mean difference: 12.94 percentage points; 95% CI: -0.34 to 26.23; p = 0.052; I 2 = 54.6%). Two studies comprising 45 animals suggested a non-significant 4.28-day reduction in time to complete closure (95% CI: -27.98 to 19.42). In the exploratory effect direction synthesis, directly attributable macroscopic healing showed a favorable direction in 17 of 22 studies and was the only domain meeting the prespecified 70% concordance threshold; four of these studies had confirmed unit-of-analysis concerns, and other reparative domains were heterogeneous. Formulation-level comparisons met the same exploratory threshold across four reparative domains, but the isolated contribution of rhPDGF-BB could not be determined. Safety reporting was sparse. Certainty for the primary outcome was very low. Conclusions : Directly attributable comparisons showed a predominantly favorable study-level pattern for macro

Despite the promise of catalytic nanozymes in treating multidrug-resistant (MDR) bacterial infections, their antibacterial efficiency is often constrained by limited catalytic activity and inefficient interfacial coupling between functional components. Herein, we engineered a Ti 3 C 2 MXene/Cobalt-based Metal-Organic Framework (Co-MOF) heterostructured nanozyme (CMX) via interfacial Ti-O-Co coordination between conductive Ti 3 C 2 MXene and redox-active Co-MOF. Different from physically mixed MXene/MOF systems or externally stimulated antibacterial nanozymes, CMX was designed to strengthen interfacial catalytic synergy, modulate the local catalytic environment of Co sites, and boost Fenton-like reactive oxygen species (ROS) generation under mild conditions. Consequently, the interface-engineered CMX system exhibits strong bactericidal activity, markedly reducing the viability of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and methicillin-resistant S. aureus (MRSA) by >99% within 2 h at 200 µg mL -1 . In vivo evaluations in rat infected wound models demonstrate that topical CMX + H 2 O 2 treatment reduced bacterial burden and showed no obvious systemic toxicity within the tested observation period. Furthermore, the CMX-based treatment alleviated local inflammation, promoted collagen deposition and angiogenesis-associated marker expression, and accelerated wound closure, reaching ∼95.2% closure by Day 10. This Ti-O-Co interface-engineered nanozyme provides a promising topical non-antibiotic strategy for antibacterial therapy and infected wound repair.

Cell-laden three-dimensional (3D) bioprinted hydrogels have emerged as a promising technique for enhanced wound healing by integrating biomaterials, living cells, and precise fabrication technology. Chronic wounds that persist for an extended period of time, especially when pathologically affected by diseases like diabetes, can pose a serious threat to patients' health. Conventional dressing materials typically fail to provide adequate mechanical strength, drug release control, and complete tissue regeneration. In contrast, 3D bioprinting can allow for the selective deposition of cells into the extracellular matrix-mimetic hydrogels, making it possible to construct biomimetic scaffolds for tissue regeneration. This review provides a clear overview of how key cellular components such as mesenchymal stem cells, adipose-derived stem cells (ADSCs), fibroblasts, and multicellular systems contribute to important wound healing processes like immunomodulation, angiogenesis, cell proliferation, and re-epithelialisation. It also explores how bioprinting factors, including bioink rheology, cross-linking methods, and processing conditions, influence printability, the structural stability of scaffolds, and cell survival. The close relationship between scaffold design and how cells respond is emphasised as a key factor in determining how effective the treatment will be. Although pre-clinical studies have shown promising results, bringing this research into real-world clinical use remains challenging due to issues like lack of standardisation, difficulties in scaling up, regulatory hurdles, and high costs.

Objective The etiology of chronic and non-healing diabetic wounds is manifold; the progression of the non-healing phenotype is strongly associated with poor vascular networks. Mesenchymal stem cells (MSCs) are reckoned as a promising therapy for wound healing, especially in angiogenesis. Here, we explored the role of CCBE1 in diabetic wound healing using human adipose-derived MSCs (hAD-MSCs). Methods Human adipose-derived hAD-MSCs were isolated and expanded through serial in vitro passaging. Cell proliferation and migration were evaluated using Cell Counting Kit-8 (CCK8) and scratch wound assays, respectively. collagen, and calcium-binding EGF domain-containing protein 1 (CCBE1) and vascular endothelial growth factor (VEGF) expression were analyzed via western blotting. Functional studies of CCBE1 were conducted using siRNA-mediated knockdown and plasmid-driven overexpression approaches. Type 2 diabetes mellitus was induced in Sprague-Dawley rats through a high-fat/high-glucose diet combined with streptozotocin administration. Full-thickness excisional wounds were generated on the dorsal skin, and the effects of CCBE1 modulation in hAD-MSCs on wound closure were examined. Reepithelialization and angiogenesis were analyzed using histological and immunohistochemical methods. Protein levels of CCBE1 and vascular endothelial growth factor (VEGF) were quantified by western blotting. Results hAD-MSCs showed a gradual decrease in cell proliferation, migrationand increased apoptosis, during advanced glycation end products (AGEs) conditions; meanwhile, CCBE1 and VEGF expression decreased The downregulation of CCBE1 inhibited cell proliferation and migration, and enhanced apoptosis, while CCBE1 overexpression enhanced proliferation and migration, and reduced apoptosis. Compared with untransduced hAD-MSCs, local subcutaneous injection of CCBE1-overexpressing hAD-MSCs accelerated wound closure, enhanced angiogenesis and reepithelialization at the wound bed, and increased VEGF l

A novel topical nanocarrier-based hydrogel system incorporating olmesartan medoxomil (OLM) was designed to enhance diabetic wound healing. OLM was efficiently encapsulated within lecithin-chitosan hybrid nanoparticles (LCNPs) and functionalized with hyaluronic acid (HA) to improve bioadhesion, biocompatibility, and sustained release. The optimized OLM-HA-LCNPs exhibited a nanoscale size of 324.28 ± 5.71 nm, a negative zeta potential (-39.64 ± 3.2 mV), and a high entrapment efficiency of 89.86 ± 3.15 %. In vitro release studies demonstrated a controlled, biphasic OLM release following Weibull kinetics, confirming diffusion erosion-controlled release behavior. Incorporation into a hydrogel base preserved pseudoplastic rheology, optimal pH (6.3 ± 0.2), and superior spreadability (35.26 cm 2 ). In streptozotocin-induced diabetic rats, the OLM-HA-LCNP hydrogel produced 93.5% wound closure after 14 days, compared with 87.6%, 77.1%, and 90.8% for the marketed reference, plain HA-LCNPs, and OLM-pure treatments, respectively. OLM-HA-LCNP hydrogel also increased CAT, SOD, and GSH levels by 2.7, 1.45, and 2.16 fold, respectively, and reduced MDA levels by 77% compared with diabetic controls. Histological and immunohistochemical findings further demonstrated improved epidermal regeneration, collagen deposition, and normalization of VEGF and MMP-9 expression. Collectively, these findings demonstrate that the OLM-HA-LCNPs hydrogel efficiently improves topical OLM delivery and therapeutic performance in diabetic wound healing.

In response to injury, cells proliferate, migrate, and invade to replace missing cells and close wounds. However, the role of other wound-induced cell behaviors is not understood, including the formation of syncytia (multinucleated cells). Here, we use in vivo live imaging to analyze wound-induced syncytia in mitotically competent Drosophila pupae. We find that almost half the epithelial cells near a wound fuse to form large syncytia. When the autophagy gene Atg1 is knocked down, fewer syncytia form, and wounds close more slowly. Further, a computational model of tissue fluidity indicates that cell fusion speeds wound closure time by about one-third. Syncytia use several routes to speed wound repair: they outpace diploid cells at the wound margin to lead the initial resealing of the wound; they reduce the need for intercalation as the tissue reshapes during closure; and they pool resources of their component cells to concentrate them toward the wound margin. In addition to wound healing, these properties of syncytia are likely to contribute to their roles in development and pathology.

We describe adhesive and self-healing hydrogels of chitosan functionalized with catechol groups (Chit-Cat) and crosslinked with β-glycerophosphate for the treatment of chronic diabetic wounds. Catechol functionalization enhanced the antibacterial activity of the hydrogels, eliminating both Gram-negative and Gram-positive bacteria while preserving excellent cytocompatibility against human dermal fibroblasts from aged diabetic donors. The efficacy of this therapeutical approach was assessed in vivo in a mice diabetic wound model. The results demonstrated that the treatment with Chit-Cat hydrogels decreased the wound area with no contraction compared to the treatment controls. Additionally, these hydrogels significantly enhanced angiogenesis in the treated wounds, decreased the pro-inflammatory macrophages, and facilitated a controlled transition from the inflammatory to the proliferative phase, characterized by an early prevalence of thick collagen fibers. These data suggest that Chit-Cat hydrogels offer a promising solution for wound dressing and the management of diabetic skin wounds, providing a multifunctional platform that accelerates and improves the healing in challenging clinical scenarios.

Pressure ulcers remain a persistent challenge in clinical care, particularly for patients with limited mobility, and accurate stage assessment from images is still difficult to achieve in practice. In this work, we investigate how the systematic integration of complementary visual cues can improve automated pressure ulcer staging. All experiments are conducted on a previously released clinical image dataset annotated according to EPUAP (European Pressure Ulcer Advisory Panel) staging standards. Instead of relying on a single modeling strategy, we explore a unified deep learning framework that gradually integrates wound localization, segmentation, and stage classification. Localization is handled using both detection- and segmentation-based approaches, while staging relies on convolutional and attention-based models. The proposed framework performs wound localization automatically and eliminates the need for manual region specification during inference. The results show that segmentation-based localization provides more reliable spatial guidance, with U-Net++ achieving a maximum Dice coefficient of 99.3%. Classification performance improves as global image context, localized wound regions, and attention mechanisms are combined. To provide a more comprehensive performance assessment, all classification models were additionally evaluated using five-fold cross-validation, and statistical significance was assessed using McNemar's exact test. The proposed attention-enhanced two-stream framework achieved 82.64% accuracy on the original train-test split and a mean five-fold cross-validation accuracy of 86.69%. Overall, the findings suggest that pressure ulcer staging benefits from looking beyond a single visual perspective. By examining how localization, feature fusion, and attention interact, this study provides practical insight into building more interpretable and clinically meaningful deep learning systems for automated wound assessment.

Ethnopharmacological relevance Centella asiatica (L.) Urb. is a medicinal herb belonging to the family Apiaceae. It is commonly known as Brahmi, Gotu kola, Ondelaga, and Indian pennywort. The plant has been extensively used in traditional systems of medicine such as Ayurveda, Traditional Chinese Medicine, and Southeast Asian folk medicine for the treatment of skin conditions, including wounds, ulcers, burns, and skin infections. Aim of the study This study aimed to conduct a systematic review and meta-analysis to evaluate the wound-healing efficacy of Centella asiatica on the basis of available preclinical evidence. Materials and methods This investigation was performed as per the PRISMA guidelines. Extensive examination of literature was performed across Medline/PubMed, Scopus, EMBASE, Google Scholar, and the Cochrane Library until 31 January 2025. The studies retrieved were filtered based on the set inclusion and exclusion criteria. Statistical meta-analysis was performed on quantitative data extracted from the studies that qualified for inclusion. Results A total of sixteen preclinical studies were identified that satisfied the criteria for inclusion and were subsequently incorporated in the meta-analysis. However, out of the sixteen studies, five studies did not have quantifiable data thus, a total of eleven studies were analyzed. The Centella asiatica treated groups, as compared to the untreated or vehicle-treated control groups, showed a significant improvement in numerous wound-healing parameters. These parameters encompassed morphological outcomes (tensile strength, epithelization period, wound contraction efficiency, and wet and dry tissue weights), biochemical markers (hydroxyproline content, collagen deposition, and tissue protein levels), and histopathological features (neovascularization, reduced inflammation, and increased fibroblast proliferation). Furthermore, three studies evaluating acute dermal toxicity according to OECD Guideline 404 found no ski

Chronic wounds represent a major global healthcare burden, affecting a large patient population worldwide. A critical barrier to effective treatment is the hostile wound microenvironment, characterized by elevated reactive oxygen species and high protease activity, which lead to rapid degradation of growth factors and extracellular matrix components, thereby limiting the efficacy of conventional therapeutic strategies. Metal ions have emerged as promising alternatives in regenerative medicine due to their relative stability in such environments and their ability to regulate multiple cellular processes involved in tissue repair. In the present study, we investigate the therapeutic potential of copper (Cu 2+ ) and zinc (Zn 2+ ) ions incorporated into a chitosan-proline scaffold for enhancing wound healing responses. These ions exhibit concentration-dependent biological effects, where controlled levels promote collagen synthesis, cell migration, and cellular proliferation, while excessive concentrations can induce cytotoxic responses. Cytotoxicity assessment of ion solutions and extracts of ion-loaded scaffolds was performed to determine optimal concentrations that support cellular viability while maintaining therapeutic activity. Ion release behaviour in different media further provided insights into the release kinetics and helped identify concentrations suitable for biological applications. In vitro wound healing assays using fibroblast and keratinocyte cell lines demonstrated enhanced cell migration and proliferation in the presence of Cu 2+ and Zn 2+ . Furthermore, treatment with these ions promoted collagen deposition in fibroblast cultures, indicating improved extracellular matrix formation. Gene expression analysis using RT-PCR revealed significant upregulation of wound healing markers, including collagen type I alpha 1 (Col1α1), heat shock protein 47 (HSP47), and vascular endothelial growth factor (VEGF) in L929 fibroblast cells. Collectively, these findings d

The healing of diabetic wounds is impeded by a pathological triad of recalcitrant bacterial infections, oxidative stress, and chronic inflammation. While photothermal therapy (PTT) is a promising non-antibiotic alternative, its clinical translation is constrained by a critical efficacy-biosafety paradox: high-temperature ablation (>60 °C) induces collateral tissue damage, whereas biosafe mild-temperature PTT ( 2 @ZnO heterostructures into a dynamic dextran (Dex) and poly(vinyl alcohol) (PVA) network (PD@MoS 2 -ZnO), executing a "sensitization-before-attack" strategy. Sustained Zn 2+ release selectively permeabilizes bacterial membranes, rendering pathogens hypersensitive to subsequent mild photothermal treatment (∼50 °C). In vitro assays demonstrated that this synergistic mechanism achieved exceptional antibacterial efficiency, eliminating 97.54% of E. coli and 98.98% of S. aureus . In a S. aureus -infected diabetic mouse model, the hydrogel treatment resulted in a 98.05% reduction in bacterial load and significantly accelerated wound closure, with the residual wound area diminishing to 1.11% after 15 days. Histological analyses further confirmed that the dressing promoted collagen deposition, re-epithelialization, and angiogenesis. This work establishes that an interfacial-sensitization platform provides a potent and biosafe strategy for managing complex diabetic wound infections without compromising host tissue viability.

One major obstacle for aged wound healing is the abnormal senescence of macrophages in chronic wounds which causes immunosenescence. Tissue homeostasis depends on regulation of metabolism in accumulating senescent cells (SnCs) with aging, and cell activation for aged tissue repair requires sufficient energy. Therapeutic advancements are potential by employing metabolic strategies for intervention. First, a disorder of arginine-oxidative phosphorylation metabolism in aging skin was found, which may be the main culprit of aging. Engineered EVs (4-octyl itaconate (4OI)-EVs) which possess naturally abundance of mitochondrial proteins have been developed here. Our findings demonstrate that 4OI-engineered EV (4OI-EV) may accelerate the repair of aged mouse skin and diabetic mouse skin, reduce cellular senescence, and recover cell dysfunctions. After 4OI-EV therapy, metabolism has been notably altered, with decreased glycolysis and increased arginine-oxidative phosphorylation axis through enhanced argininosuccinate synthetase 1 (ASS1) level. We demonstrate how 4OI-EV partially restores macrophages senescence by reversing mitochondrial dysfunctions and mitophagy suppressions via ASS1 which may be identified as a potential effective target for alleviating skin aging.

Covalent organic frameworks (COFs) with tailorable functional architectures hold promise in biomedical fields, while the conventional powdery morphology restricts practical use. In this study, a porphyrin-based COF with abundant amino groups has been synthesized through a defect engineering strategy, which further reacts with hyaluronic acid (HA) through an amide condensation reaction to obtain a COF-HA hydrogel. The hybrid hydrogel retains the photochemical properties of porphyrin-based COFs and is also endowed with the advantages of hydrogels, including good adhesion, plasticity, and biocompatibility. The hybrid material exhibits excellent photothermal conversion performance, achieving a temperature elevation of 29 °C under 808 nm laser irradiation (2 W/cm2) within 5 min. Additionally, the composite achieves complete antibacterial efficacy against Staphylococcus aureus and Escherichia coli under 10 min of the NIR irradiation. Furthermore, as a wound dressing, the composite hydrogel can effectively alleviate inflammatory response in S. aureus-infected cutaneous wounds, thereby contributing to prominent acceleration of wound healing and skin regeneration. This work broadens the translational prospects of porphyrin-functionalized COFs for antibacterial treatment and wound repair applications.

The aim of this study was to develop a multifunctional, biodegradable wound dressing combining microbial protection, structural integrity, moisture regulation, bioactive compound delivery, and degradability within a single platform. Free-standing cross-linked films were fabricated by sequential solvent casting of two oppositely charged polymeric solutions: an anionic CMC/hyaluronate matrix containing sericin and Helix aspersa Müller secretion filtrate (SSF), and a cationic chitosan solution. Formulation was optimized in terms of composition, SSF incorporation into the anionic or cationic solution, and film thickness. The resulting films prevented penetration of the tested bacterial strains (S. aureus and P. aeruginosa) for 24 h, regardless of SSF localization. Compared with uncross-linked chitosan-free formulations, cross-linking markedly improved structural stability while preserving high swelling capacity and susceptibility to oxidative degradation. Film composition and thickness modulated swelling, degradation kinetics, and moisture regulation. ATR-FTIR and SEM analyses supported partial penetration of chitosan into the anionic matrix, resulting in a cross-linked region and a distinct bilayer architecture. The films also exhibited suitable mechanical performance, UV barrier properties, and transparency. Release studies demonstrated rapid protein release, predominantly represented by sericin. The released components showed good cytocompatibility toward HaCaT cells, while scratch assays demonstrated significantly enhanced keratinocyte migration. Sericin emerged as the main contributor to this effect, whereas SSF alone showed no significant pro-migratory activity. Overall, this study provides proof of concept for a multifunctional wound dressing combining microbial barrier function, susceptibility to degradation under simulated oxidative conditions, moisture management, tunable physicochemical properties, and bioactivity.

An excisional wound is characterised as a complete loss of tissue from its site and involves a complex healing process. Conventional wound dressings present significant clinical challenges, including delayed re-epithelialization, an increased risk of infection, and excessive scarring. Electrospun biopolymer/nanofiber scaffolds developed by electrospinning have emerged as a promising class of advanced wound dressings with a unique extracellular matrix (ECM)- mimicking nanofibrous architecture, high porosity, and tunable physicochemical properties. The activity of electrospun nanofibres depends on the design, functionalization, and formulation strategies (technique & process parameters). The incorporation of growth factors, cytokines, drugs, phytochemicals, and antimicrobial agents enables controlled, phase-specific modulation of inflammation, angiogenesis, and tissue remodelling. Preclinical evidence consistently demonstrates that electrospun scaffolds accelerate wound closure, enhance re-epithelialization, promote neovascularization, and improve collagen organisation and mechanical strength. However, no human clinical trials specifically evaluating electrospun bio-/nanofiber scaffolds for excisional wound healing have been reported to date, representing a major translational gap between promising preclinical findings and clinical application. The review critically explains the integration of the electrospinning technique for fabricating bio-/nanofibers as scaffolds for advanced excisional wound dressings, linking process parameters to scaffold architecture and phase-specific tissue repair mechanisms. Despite significant advantages, key challenges like immunocompatibility, manufacturing scalability, regulatory classification, and long-term safety can be resolved by complying with the FDA and EMA wound dressing regulatory frameworks. Emerging trends in smart, bioactive, and stimuli-responsive electrospun scaffolds are highlighted as future directions toward clinically

Chronic diabetic wounds remain refractory to healing due to persistent inflammation, impaired re-epithelialization, extracellular matrix dysregulation, and microvascular dysfunction. Here, we report a mechanically robust and biologically integrated microneedle (MN) platform composed of a poly(ε-caprolactone) (PCL) core and a gelatin methacryloyl (GelMA) coating, engineered for the localized compartmentalized co-delivery of deferoxamine (DFO) and mesenchymal stem cell-derived conditioned medium (CM). By leveraging a dual-reservoir architecture-incorporating fresh liquid CM within the GelMA shell and lyophilized CM within the structural PCL core-the platform achieves complementary biphasic release kinetics while preserving the biological integrity of labile growth factors. In a diabetic wound model using Wistar rats, treatment with a bioactive MN platform significantly accelerated re-epithelialization, resolved chronic inflammation, and increased collagen deposition by approximately 40% compared to untreated and blank MN controls. Furthermore, vascular assessment on day 14 revealed a qualitative increase in CD31-positive vascular structures within the treated wounds. Notably, microneedles co-loaded with DFO and CM markedly improved key healing parameters compared with untreated diabetic wounds, with several parameters approaching those observed in non-diabetic control tissues at the 14-day endpoint. Mechanistically, these findings are consistent with a hierarchical healing process in which restoration of immune homeostasis promotes epithelialization and extracellular matrix remodeling, followed by enhanced vascularization. Collectively, these results indicate that spatially compartmentalized MN-mediated co-delivery of DFO and CM may represent a promising strategy for activating endogenous regenerative pathways and enhancing tissue repair in diabetic wounds. This approach may also provide a scalable therapeutic platform for improving the impaired healing capacity assoc

Chronic cutaneous wounds remain a major clinical challenge due to a persistent pro-inflammatory microenvironment characterized by unresolved inflammation and dysregulated macrophage polarization. Emerging "immune-instructive" biomaterials offer a promising strategy to actively modulate host immune responses rather than providing mere structural support. In this study, we performed a comparative screening of representative traditional Chinese medicine (TCM)-derived monomers, identifying baicalin (BAL) as the most potent regulator of macrophage polarization. To ensure localized and sustained bioactivity, BAL was encapsulated into mesoporous silica nanoparticles (MSNs) and subsequently integrated into electrospun poly(ε-caprolactone)/silk fibroin (PCL/SF) nanofibrous membranes to construct a hierarchical bioactive system (BA@MSN/PCL/SF). Mechanistic investigations combining network pharmacology, molecular docking, and pharmacological inhibition revealed that BAL directs macrophage polarization toward a pro-regenerative M2 phenotype via the PI3K/AKT/GSK3β signaling axis. In vitro , the composite membranes exhibited excellent cytocompatibility and effectively modulated inflammatory responses. In a murine full-thickness wound model, BA@MSN/PCL/SF membranes significantly accelerated wound closure, enhanced granulation tissue formation, and promoted high-quality collagen deposition and skin appendage regeneration. These therapeutic effects correlated with a pronounced shift in the local immune microenvironment, evidenced by increased ARG1 + and decreased iNOS + macrophage populations. Our findings demonstrate that integrating potent natural immunomodulators with controlled-release hierarchical scaffolds provides a sophisticated strategy for engineering immune-instructive wound dressings, offering a mechanistic basis for modernizing traditional therapies in regenerative medicine.

Wound healing is a highly organised biological event that involves hemostasis, inflammation, proliferation, and tissue remodelling processes. Dysregulated wound healing leads to the development of chronic wounds, characterised by persistent inflammation, impaired tissue regeneration, and extensive fibrosis. Recently, inflammasomes, which act as key regulators of innate immunity, have attracted increasing attention due to their important roles in wound healing. Indeed, inflammasome complexes, including NLRP3, AIM2, NLRC4, NLRP1, and Pyrin, activate inflammatory caspases, particularly caspase-1, which cleaves pro-IL-1β and pro-IL-18 into their mature, biologically active forms and promotes gasdermin D-dependent pyroptosis. Although transient inflammasome activation contributes to protective early inflammatory responses, including pathogen clearance and tissue repair, sustained or dysregulated activation promotes inflammatory caspase activation and pyroptosis, resulting in persistent inflammation, tissue injury, and aberrant extracellular matrix remodelling that can ultimately contribute to fibrosis and chronic wound development. This review focuses on state-of-the-art studies on the roles of inflammasome-derived biomarkers in wound healing. We highlight inflammasome-associated molecules as potential biomarkers of wound inflammation and tissue injury, while distinguishing their roles as mechanistic mediators from their potential as therapeutic targets. These include sensors, adaptors, inflammatory caspases, pyroptosis-related mediators, cytokines, and oxidative stress-associated factors. Our review highlights transcriptomic, proteomic, and metabolomic approaches for identifying candidate molecular biomarkers, while single-cell RNA sequencing and spatial transcriptomics provide cell-specific and spatial information that can improve biomarker validation and clinical stratification of wound states. Additionally, we discuss shared inflammasome-mediated mechanisms across di

Chronic wound infections are difficult to treat due to the polymicrobial biofilms that delay wound healing increasing antimicrobial tolerance and limiting patient compliance. To address this challenge, we developed a non-antibiotic combination of Graphene Oxide (GO) and Methylglyoxal (MGO) (patent N. 102022000024408-Composizione per il trattamento delle infezioni a carico delle lesioni cutanee) against clinically relevant chronic wound pathogens. For the tests, clinical antimicrobial resistant Staphylococcus aureus and Pseudomonas aeruginosa were used. MGO MIC was determined and the best GO + MGO combination, evaluated by using checkboard test, was tested in terms of: i) fluid membrane changes; ii) S. aureus and P. aeruginosa CFUs/mg reduction in Lubbock Chronic Wound Biofilm-LCWB, a recognized polymicrobial in vitro chronic wound biofilm model; iii) P. aeruginosa motility. MGO MIC values ranged from 32 to 128 mg/l. Notably, synergistic interactions between GO and MGO were observed exclusively against S. aureus, whereas the combinations showed additive effects against P. aeruginosa. The best GO + MGO (6.25 + 64 mg/l) combination increased bacterial membrane fluidity, inhibited informing and mature LCWBs by 60-80% in terms of CFU/mg and P. aeruginosa twitching motility. GO + MGO combination exhibited an additive antimicrobial/antibiofilm activity with a multi-target action. Overall, the GO + MGO combination, at recognized non-toxic concentrations, is a valid and innovative non-antibiotic solution for wound management affecting the polymicrobial chronic wound biofilms and P. aeruginosa motility.

Carbon quantum dots (CQDs), a novel class of nanomaterials, have received significant attention due to their unique properties, including excellent biocompatibility, low toxicity, and strong fluorescence. In this study, CQDs were integrated into a hybrid hydrogel matrix composed of carboxymethyl cellulose (CMC) and the bioactive components of aloe vera (AV) to leverage their synergistic wound healing and antimicrobial potential. AV, a renowned medicinal plant, has been traditionally used for wound healing. CMC, a versatile polymer, has excellent biocompatibility and moisture retention capabilities. The combination of AV, CMC, CQD and quercetin in a hydrogel formulation presents a promising approach for enhancing wound healing. In this study, we have synthesized CQDs and characterized them with X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), photoluminescence (PL), ultraviolet-visible spectroscopy (UV), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDAX) and RAMAN spectroscopy. CQDs show very good antimicrobial properties against wound pathogens such as Escherichia coli , Enterococcus faecalis , Staphylococcus aureus , and Pseudomonas aeruginosa , studied through well diffusion, colony-forming unit (CFU), growth curve, biofilm assay, reactive oxygen species (ROS), cell membrane integrity, protein leakage, extracellular polymeric substances (EPS), and lipid peroxidation assessing its ability to inhibit infections in wounds. The synthesized hydrogels were evaluated in vitro for their morphology, antibacterial activity, swelling behavior, degradation profile, and rheological properties. The AV/CMC/CQD/QUECERTIN hydrogels show enhanced wound healing in in vivo wound healing experiments on albino Wistar rats with 89% wound closure on day 13 compared to the control which has only 58% wound closure.

Magnesium ions (Mg 2+ ) promote angiogenesis in wound healing, yet direct Mg salt incorporation causes burst release that limits efficacy. Herein, a composite delivery system SA/Gel@PM: Mg-loaded poly(ethylene glycol) diacrylate (PEGDA) microspheres embedded in a sodium alginate/gelatin (SA/Gel) hydrogel, that achieves dual-stage sustained Mg 2+ release was reported. Food-grade peanut oil served as a biocompatible substitute for cytotoxic n-hexadecane in the continuous phase of a flow-focusing microfluidic device, enhancing PEGDA microsphere production throughput (droplet interval reduced from 260 ms to 232 ms). COMSOL-optimized flow rates (75:7.5 μL/min) yielded monodisperse PEGDA microspheres (140-170 μm). Magnesium salts were then loaded into the PEGDA microspheres by the immersion-precipitation method. SA/Gel@PM retained a 3D porous structure with ∼2000% swelling and strong exudate uptake. In vitro, the SA/Gel matrix of SA/Gel@PM further retarded Mg 2+ release compared to PM microspheres alone, thereby mitigating the initial burst effect (reducing the 4 h release of PM-10 from 39.1 to 13.9 μg/mL). CCK-8 assays with L929 fibroblasts showed >80% viability on day 1 and > 90% on day 3 for all SA/Gel@PM samples. In vivo, SA/Gel@PM-10 achieved 94.69% wound closure on day 10 with near-normal tissue remodeling. This microsphere-in-hydrogel dual-release platform offers a safe, tunable dressing strategy for Mg 2+ -enabled wound healing and related immunological regulation.

Burn wounds were often entrapped in inflammatory cascades and highly vulnerable to bacterial infection. Meanwhile, accumulated necrotic tissue and impaired vessels further aggravated local ischemia, thereby impeding the wound healing process. Herein, a sprayable hydrogel based on EGCG-grafted oxidized alginate/carboxymethyl chitosan/platelet exosomes (AECP hydrogel) was fabricated. Covalent grafting of EGCG onto alginate endowed an AECP hydrogel with a controllable release profile for a sustained functional effect of EGCG. Due to the inherent bioactivity of EGCG, the AECP hydrogel could eliminate bacteria, scavenge intracellular ROS, and promote macrophage polarization. Moreover, the introduced platelet exosomes significantly upregulated angiogenesis-related gene expression in HUVECs. 3D cell encapsulation demonstrated that the AECP hydrogel supported cell proliferation and spreading, conducive to exerting the biological functions of cells recruited to the wound site. Additionally, an AECP hydrogel precursor could be conveniently sprayed onto irregular wounds and in situ form a protective barrier via dynamic hydrogen bond interactions and Schiff base reactions. In vivo experiments confirmed that sprayable AECP hydrogel accelerated burn wound closure through enhanced collagen deposition, granulation tissue formation, macrophage polarization, and neovascularization. Overall, this work presents a sprayable EGCG-grafted, platelet exosome-incorporated alginate hydrogel with integrated immunoregulatory and proangiogenic properties, holding substantial potential for clinical burn wound management.

Delayed corneal wound healing and sensory neuropathy are hallmarks of diabetic keratopathy, yet the role of corneal epithelial cell (CEC)-derived exosomes in these processes remains unclear. This study characterized exosomes secreted by the mouse corneal epithelial progenitor cell line TKE2 at either quiescent state or scratch-wounded. The isolated extrasellar vesicles wer characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Exosomal cargo was analyzed by LC-MS/MS proteomics. The roles of exosome and selected proteins were assessed for effects on wounded healing of normoglycemic and streptozotocin-induced diabetic C57BL/6J mice. The isolated vesicles exhibited canonical exosomal features and were readily taken up by CEC at 1 dpw and trigeminal sensory neurons at 3 dpw. Exosomes derived from healing, but not quiescent, cultures accelerated delayed epithelial wound closure in diabetic corneas, while having little effect on normoglycemic corneas. HTRA1, enriched in healing exosomes, contributed to epithelial wound healing in normal corneas, as its inhibition attenuated wound closure in normoglycemic but not diabetic mice. In contrast, treating healing exosomes with a STAT3 inhibitor, which permanently blocks its activity without altering protein content, partially reduced exosome-mediated wound healing in diabetic corneas. Collectively, these findings support context-dependent effects of CEC-derived exosomes in corneal wound repair and suggest that exosomal components may contribute to the regulation of diabetic corneal wound healing.

Large-scale acute or chronic wounds often exhibit impaired closure due to delayed re-epithelialization, weakened skin contraction, and persistent inflammation. To address this challenge, we report a dual-modal mechano-electrical hydrogel that integrates multifunctional properties, including active wound contraction, intrinsic antibacterial protection, and efficient electrical modulation. Specifically, the hydrogel is composed of poly(N-isopropylacrylamide) (PNIPAm), poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), and quaternary ammonium-functionalized hyaluronic acid (MPTC-HA) microgels, where the PNIPAm chains enable temperature-triggered active contraction to remold the wound mechanical microenvironment; PEDOT:PSS forms a mixed ionic-electronic conductive network that promotes fibroblast/keratinocyte migration and re-epithelialization; MPTC-HA microgels offer tissue adhesion and antibacterial protection. Attributed to the synergy of the three components, wound closure is significantly accelerated with reduced scar formation, with the wound monitored via in situ impedance sensing. Additionally, the hydrogel can also function as a flexible epidermal bioelectrode for electrophysiological signal acquisition owing to its low interfacial impedance. These findings underscore its clinically translational potential as a bifunctional integrated platform for tissue regenerative therapy and wearable bioelectronics.

Moisture-driven power generation from wound exudate provides a promising route toward in situ self-powered wound therapy. However, its performance is limited by environmental factors, especially elevated external temperatures, which impairs water retention and disrupts humidity gradients, consequently degrading power output. Here we demonstrate a heterogeneous short-fiber humidity-powered band-aid integrated with radiative cooling technology (CE band-aid). Results show that the degradable gelatin/Poly(L-lactic acid) (PLLA)/MXene scaffold generates an open-circuit voltage of ∼120 mV and a current of ∼12 µA under wet conditions. A surface layer of polyethylene-particle-modified fibers (PLLA/PE) endows the device with high solar reflectivity (∼98%) and mid-infrared emissivity (∼93%). Under outdoor sunlight, the PLLA/PE layer maintains a surface temperature ∼10°C below ambient levels and retains 10% more moisture than commercial gauze. In rat and pig full-thickness skin defect models, PLLA/PE reduces skin temperature by up to 6.5°C, and this cooling effect significantly suppresses inflammation. Compared with other groups, the CE Band-aid upregulates the Pi3K-Akt signaling pathway via continuous electrical stimulation, promotes tissue regeneration, and inhibits apoptosis-related signaling pathways, thereby significantly shortening wound healing time. This work presents a novel, zero-energy strategy for accelerated wound regeneration.

Infected wound treatment requires multifunctional biomaterials to combat infection, oxidative stress, and impaired tissue repair. Bacterial cellulose (BC) provides a hydrated nanofibrous scaffold for wound dressings; however, its functionalization often suffers from inefficient incorporation of poorly water-dispersible bioactives and harsh purification procedures. Here, we developed a fermentation-integrated strategy that combines the submerged BC-forming capability of Kosakonia oryzendophytica FY-07 with xanthan-gum-assisted dispersion of plant-derived bioactives and temperature-triggered bacterial autolysis for in situ fabrication of functional BC composites. Alkaloid-rich Coptis chinensis extract and polyphenol-rich pomegranate peel extract were incorporated during BC biosynthesis, followed by mild enzymatic purification. The resulting membranes achieved high bioactive incorporation efficiencies of 89.73% and 94.61%, respectively, and exhibited sustained release behavior. The incorporated bioactives endowed BC membranes with enhanced antioxidant and antibacterial activities, while maintaining favorable cytocompatibility and hemocompatibility. In particular, the pomegranate peel extract-incorporated membrane showed strong radical-scavenging capacity, achieving DPPH• and ABTS• + scavenging rates of 97.64% and 95.22%, respectively. Moreover, the engineered FY-07 strain enabled temperature-triggered autolysis, resulting in an approximately 5.1-log reduction in viable cells and facilitating mild downstream purification. In a Staphylococcus aureus-infected full-thickness wound model, the composite membranes effectively promoted wound healing. This work establishes a fermentation-integrated manufacturing platform that couples microbial BC production with in situ incorporation and controlled delivery of natural bioactives, providing a sustainable approach for the fabrication of multifunctional BC-based wound biomaterials.

Wound healing is a complex biological process where uncontrolled inflammation often delays tissue repair, imposing a significant clinical and economic burden worldwide. This study aimed to develop and evaluate almond gum (Prunus dulcis) based silver and zinc oxide nanobiocomposites (AG-Ag and AG-ZnO) through integrated computational, In-vitro and In-vivo studies as a promising therapeutic approach for accelerating wound healing. This study is the first to comparatively evaluate Ag-NPs and ZnO-NPs within the same almond gum matrix. A total of 31 phytoconstituents of Prunus dulcis were screened for ADME properties via pkCSM, and potential bioactive compounds were docked against COX-2, TNF-α, and VEGFR-2. Quercetin-3-diglucoside and Corosolic acid recorded the strongest binding affinities toward COX-2 (- 8.8 kcal/mol), mechanistically supporting the anti-inflammatory basis of Prunus dulcis. The green-synthesized nanobiocomposites were characterized via UV-Vis spectroscopy, FTIR, XRD, SEM, zeta sizer, and zeta potential, with mean particle sizes of 73.33 nm and 225.2 nm for AG-Ag and AG-ZnO, respectively. In-vitro studies revealed strong antioxidant activity, with AG-ZnO exhibiting the highest TPC (342.29 ± 1.18 µg GAE/g) and TFC (158.20 ± 0.40 µg CE/g), and AG-P the lowest DPPH IC50 (47.67 ± 2.01 µg/mL). Both nanobiocomposites further demonstrated potent antibacterial and anti-biofilm activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Bacillus subtilis, alongside significant anti-inflammatory activity and negligible hemolytic toxicity. In vivo evaluation using a rabbit excisional wound model demonstrated superior wound contraction with AG-Ag (90%) and AG-ZnO (93%) compared to the standard drug Polyfax (68%) and untreated control groups. Treatment groups also showed significant modulation of inflammatory biomarkers (ESR, CRP, IL-6) at Days 7 and 15 compared to controls. Histopathological studies showed active collagen deposition, fibr

Diabetic wounds continue to present a clinical challenge in that the persistent inflammatory state, oxidative stress, hyperglycemia, impaired angiogenesis, infection, and defective ECM remodelling all contribute to delayed tissue repair. The purpose of this review is to critically assess recent research on MXene-based multifunctional wound-dressing materials employed for diabetic wound management and their therapeutic mechanisms, smart sensing, drug delivery, material integration, safety, preclinical evaluations, and translation challenges. The high surface area, surface chemistry control ability, electrical conductivity, photothermal response, and ability of MXenes to adhere with polymeric biomaterials have generated a great attraction. Recent advancements in hydrogels, patches, microneedles, smart bandages, drug delivery platforms, and biosensing platforms are reviewed, focusing on redox regulation, immunomodulation, angiogenesis, antibacterial activity, ECM remodelling, controlled drug release, and real-time wound monitoring. The impact of MXene loading, structural properties, terminations, and composite structure on the dressing performance is also discussed. Biological performance in terms of long-term biocompatibility, degradation and clearance, sterilization, storage stability, and preclinical models are evaluated. Even though promising results are apparent in preclinical studies, evidence on short- and long-term safety, functional vascular perfusion, standardized criteria of efficacy, large animal validation, and clinical superiority compared to established wound-care approaches is scarce. Reproducible manufacturing, clinically relevant models, standardized evaluation, well-designed clinical trials, and rigorous safety assessment should be priorities for future studies to advance translation to patients with diabetic wound disease.

Chronic diabetic wounds remain a major clinical challenge due to persistent inflammation, excessive reactive oxygen species (ROS), and impaired angiogenesis. However, many wound dressings do not coordinate therapeutic delivery with the changing oxidative and angiogenic requirements of diabetic wound healing. Herein, we developed a sandwich-structured composite dressing ( DFO PLGA@ C Gel) that enables spatiotemporally coordinated drug delivery to match the stage-specific demands of wound healing. The outer hydrogel layer, formed via dynamic Schiff-base crosslinking between oxidized sodium alginate (OSA) and chitosan, provides favorable injectability, tissue adhesion, and microenvironment responsiveness. Incorporation of curcumin nanocrystals into the OSA/chitosan hydrogel further improves drug dispersion and bioavailability, enabling rapid ROS scavenging and attenuation of early-stage inflammation. Meanwhile, the inner electrospun PLGA nanofiber membrane provides sustained deferoxamine (DFO) release, which was associated with increased HIF-1α expression and enhanced angiogenesis during the proliferative phase. This temporally programmed strategy synchronizes anti-inflammatory and pro-angiogenic processes, facilitating the transition from inflammation to tissue regeneration. In diabetic wound models, DFO PLGA@ C Gel reduced intracellular oxidative stress, increased angiogenesis-related signals and vessel density, and accelerated wound-area reduction. Overall, this work highlights the importance of temporal regulation in biomaterial design and presents a promising platform for precise microenvironment modulation and chronic wound therapy.

Guidelines for the diagnosis and treatment of diabetic foot ulcers and gangrenes, third edition, are fully revised guidelines drafted by the Japanese Dermatological Association Wound/Pressure Ulcer/Burn Guidelines Drafting Committee. They were developed in a systematic and transparent manner with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. In the three clinical questions with meta-analyses, imaging procedure for osteomyelitis, topical negative-pressure wound therapy, platelet-rich plasma thrapy, were weakly recommended in the diagnosis and treatment of diabetic foot ulcers and gangrenes. General information on diagnosis, prevention, assessment, and unconventional treatment of diabetic foot ulcers and gangrenes was also provided.

Aims Patients with diabetic foot ulcer (DFU) complicated by chronic kidney disease (CKD) have poor survival, yet nonlinear prognostic evidence of estimated glomerular filtration rate (eGFR) in this population remains limited. This study aimed to characterize the eGFR-all-cause mortality association in a multidisciplinary-managed DFU cohort. Material and methods In this retrospective cohort, 595 hospitalized DFU patients were enrolled. Restricted cubic spline (RCS), Kaplan-Meier, and multivariable Cox regression were applied to assess survival and independent predictors. Sensitivity and subgroup analyses were performed to confirm result robustness. Results A significant nonlinear eGFR-mortality relationship was observed (P for nonlinearity 2 (log-rank p 2 , adjusted HRs were 2.59 (95% CI: 1.34-4.98, p = 0.004) for eGFR 30- 2 and 4.67 (95% CI: 2.63-8.30, p 2 . Advanced age, lower BMI and reduced serum albumin independently predicted mortality. Sensitivity analyses confirmed result robustness, while subgroup interaction analyses revealed minimal outcome heterogeneity apart from sex-related effect modification. Conclusions DFU patients with eGFR 2 face substantially higher long-term all-cause mortality. Our findings support extending the "renal foot" phenotype to CKD Stage 3b and above. Routine eGFR evaluation aids early risk stratification and tailored multidisciplinary DFU-directed clinical care.

Diabetic Foot Ulcer (DFU), a severe chronic diabetes complication with low healing and high recurrence rates, is a major global health challenge. Overexpression of matrix metalloproteinase-9 (MMP-9) and the consequent MMP-9/TIMP1 (tissue inhibitor of metalloproteinase 1) imbalance delays healing by degrading the extracellular matrix, impairing granulation tissue formation, and exacerbating inflammation. Conventional therapies do not dynamically respond to fluctuating protease levels in chronic wounds. This study introduces an MMP-9-responsive protein release system (M9RR), where the therapeutic protein (i.e., TIMP1) is linked to a membrane-anchoring domain at its C-terminus via an MMP-9-cleavable peptide, thereby exposing the fusion protein to the extracellular side of cell membranes. The system enables targeted release of TIMP1 in high-MMP-9 microenvironments, thereby neutralizing excessive MMP-9 activity. In vitro, M9RR demonstrates MMP-9 specificity, broad mammalian cell applicability, and protection of HaCaT keratinocytes and BJ fibroblasts from MMP-9-induced damage. In db/db diabetic mice, the MMP-9-responsive TIMP1 release system (TIMP1 M9RR ) significantly improves wound contraction, granulation tissue formation, epithelial regeneration, and collagen remodeling. Additionally, a cryomicroneedle (CryoMNs)-based co-delivery system for basic fibroblast growth factor (bFGF) and TIMP1 M9RR shows effective diabetic wound healing. This modular M9RR system offers a precise, adaptive therapeutic strategy for DFU and holds promise for other MMP-related diseases.

For healing full-thickness skin defects caused by severe injury, skin substitute grafts with structural and compositional biomimicry are critical. Vascularized spheroids, as highly active biological building blocks, can be applied in biomanufacturing to fabricate functional repair constructs. However, current methods of biofabricating endothelialized spheroids still face multiple technical limitations, including low throughput, poor uniformity, and insufficient controllability and observability. Furthermore, there is inadequate control over the spatial arrangement of the spheroids during vascularized construct biomanufacturing. We proposed a synergistic, shape-controlled spheroid-hydrogel biomanufacturing method to address these issues, and developed a highly integrated, one-stop bioprinting platform for spheroids (OBPS) with real-time monitoring. We focused on key biomanufacturing stages, spheroid fabrication, bioprinting, and in vivo validation, to establish an integrated technical framework providing for 'fabrication-culture-assembly-application.' Using the OBPS, we fabricated endothelialized spheroids by co-culturing human fibroblasts and human umbilical vein endothelial cells, printed fibrinogen-supplemented gelatin methacryloyl hydrogel, and bioprinted spheroids and hydrogels in situ onto full-thickness skin defects in nude mice. Animal experiments show that shape-controlled endothelialized spheroids significantly accelerated wound closure, suppressed inflammation, promoted neovascularization and collagen remodeling, and exhibited excellent tissue integration and repair potential. The OBPS system provides a novel and effective treatment for wound healing.

Bacterial infection is a major cause of delayed wound healing, while overuse of antibiotics has accelerated the emergence of antimicrobial resistance. Developing multifunctional antibacterial biomaterials that eradicate bacteria without relying on conventional antibiotics is therefore highly desirable. Herein, we report an injectable polyethylene glycol (PEG)-based hydrogel incorporating gold nanorods (ARs) and a DNA nanostructure-mediated silver and antisense oligonucleotide delivery system (A-C@Ag) to achieve synergistic antibacterial therapy and enhanced skin regeneration. The hydrogel is formed by rapid thiol-maleimide crosslinking of PEG precursors containing AR@A-C@Ag, providing excellent injectability, biocompatibility, and mechanical stability. Upon near-infrared irradiation, the AR generates mild photothermal heating to directly damage bacteria and simultaneously promotes the on-demand release of Ag + and antisense oligonucleotides from the DNA nanostructure, resulting in markedly enhanced antibacterial activity against both Staphylococcus aureus and Escherichia coli by facilitating bacterial membrane disruption. In a S. aureus -infected full-thickness wound model, AR@A-C@Ag/Gel under NIR irradiation significantly accelerated wound closure by efficiently eliminating bacteria, suppressing inflammation, promoting angiogenesis and collagen deposition, and facilitating the regeneration of skin appendages. This work demonstrates that integrating DNA nanostructure-enabled drug delivery with mild photothermal therapy represents an effective strategy for constructing antibiotic-free antibacterial hydrogels for infected wound repair.

Diabetic wounds are persistently exposed to pathological microenvironments, such as hyperglycemia and excessive ROS accumulation, which result in insufficient angiogenesis and restricted cell migration, representing a prominent challenge in clinical wound repair. Traditional wound dressings primarily focus on passive coverage and exudate absorption, making it difficult to actively regulate the microenvironment of diabetic wounds. Therefore, in this study, platinum nanozyme (PtNP)-loaded methacrylated gelatin (GelMA) microneedles (Pt-GelMA microneedles) were constructed, aiming to synergistically accelerate diabetic wound healing by leveraging the local penetration and delivery capacity of microneedles and the hydrogen peroxide decomposition capacity of PtNPs. In vitro assays demonstrated that the Pt-GelMA microneedles have favorable cytocompatibility and can alleviate oxidative stress, promote the migration of wound repair related cells and enhance the tube formation of endothelial cells. Furthermore, in a streptozotocin-induced diabetic full-thickness skin wound model, the Pt-GelMA microneedles significantly accelerated wound closure, and promoted collagen deposition and angiogenesis, without inducing evident hepatorenal toxicity. This study provides new insights into the treatment of diabetic wounds.

The capability to simultaneously promote wound healing and enable real-time monitoring is critical for effective wound management, especially in dynamic and infection-prone regions such as joints, yet unmet needs remain in clinical practice. Herein, we present a multifunctional hydrogel dressing composed of gold nanoparticles (AuNPs), Ti 3 C 2 T x MXene, poly(acrylamide), and platelet-rich plasma (PRP), designed to both accelerate tissue regeneration and provide continuous physiological monitoring. The integration of surface-functionalized MXene and AuNPs introduces both dynamic and covalent bonding connections (hydrogen, covalent, and Au─S bonds), endowing the hydrogel with remarkable stretchability (∼1000%), rapid self-healing, and robust wet tissue adhesion to accommodate skin deformation during motion. PRP further enhances angiogenesis, collagen remodeling, and cell proliferation, significantly improving in vivo healing outcomes. Crucially, the hydrogel's conductive and thermo-responsive matrix enables resistance-based sensing of local temperature changes, offering continuous, noninvasive feedback on wound status. This dual-functional platform unites regenerative bioactivity with electronic responsiveness, addressing urgent clinical needs for adaptive healing and intelligent diagnostics, which is thus providing a promising strategy for next-generation smart dressings in wearable and personalized medicine.

Chronic wound healing is often delayed due to the inability of conventional dressings to provide a suitable extracellular matrix (ECM) microenvironment that supports the survival and function of endogenous cells. This deficiency leads to persistent inflammation, impaired angiogenesis, and excessive reactive oxygen species (ROS) production, forming a vicious cycle to exacerbate tissue damage. Herein, we propose a dual-crosslinked injectable dynamic polysaccharide hydrogel. Leveraging anti-inflammatory oxidized xyloglucan, and carboxymethyl chitosan to construct a first dynamic network based on Schiff-base chemistry, this biomimetic extracellular matrix mimics dynamic changes to promote cell proliferation and resolve inflammation. Furthermore, strontium ions with pro-angiogenic activity and protocatechualdehyde with antioxidant activity serve as crosslinking points for the second dynamic network. This design ensures spatiotemporal alignment between material mechanics and therapeutic action, effectively disrupting the vicious cycle of persistent inflammation, oxidative stress, and impaired angiogenesis in chronic wounds. Additionally, this hydrogel possesses commendable self-healing, tissue-adhesive and antibacterial properties. RNA sequencing analysis revealed that the hydrogel interrupts the inflammatory cascade, modulates immune processes, and accelerates collagen deposition and angiogenesis, promoting chronic wound healing. Collectively, these findings establish a foundation for designing straightforward and multifunctional hydrogel dressings capable of accelerating chronic wound repair by establishing a regenerative microenvironment.

Diabetic wounds are typified by hyperglycemia, hypoxia, chronic inflammation, and elevated oxidative stress, all of which collectively contribute to delayed and dysregulated healing. Inspired by the structural and functional attributes of native skin, we designed a dynamic bond-crosslinked, injectable, and in situ-forming polyurethane/hyaluronic acid-based hybrid hydrogel (PUS-OHABE). In this hydrogel, caffeic acid phenethyl ester (CAPE) was grafted onto aldehyde-modified hyaluronic acid (HA) chains through dynamic borate ester bonds. This CAPE-modified HA was then combined with a side-chain hydrazide (ADH)-modified waterborne polyurethane emulsion via Schiff base reactions to form a stable hydrogel network structure. The PUS-OHABE hydrogel exhibits good self-healing ability, stability, tissue adhesion, and hemostatic capacity. Additionally, it has a unique ability to dissociate borate ester bonds in the hyperglycemic wound microenvironment to responsively release CAPE, thereby conferring antioxidant and anti-inflammatory properties. In diabetic rat models, the PUS-OHABE hydrogel enabled rapid wound healing and re-epithelialization; meanwhile, it also promoted angiogenesis, hair follicle regeneration, and extracellular matrix remodeling, thus offering a promising strategy for the design of biomaterials targeting chronic wound healing.

Wound infections caused by fungi and bacteria remain a major global health challenge. In this study, 2,6-dimethoxy-1,4-benzoquinone (DMBQ) was isolated from Ilicis Rotundae Cortex (IRC). The compound yields inhibitory effects on Candida albicans (C. albicans), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). Specifically, DMBQ disrupts the cell membrane structure of fungi and bacteria, alters membrane permeability, and induces intracellular reactive oxygen species (ROS) accumulation. In addition, DMBQ effectively suppresses the biosynthesis of fungal ergosterol and bacterial fatty acids. The synergistic action of these multiple mechanisms contributes to the antimicrobial effects of DMBQ. We further fabricated DMBQ-loaded photocurable hydrogel microneedles, HA-GMA-DMBQ MNs (HGD MNs). The covalently cross-linked network of HGD MNs boosts mechanical strength, allowing efficient stratum corneum penetration. HGD MNs exert certain in vitro antimicrobial activity, regulate the wound inflammatory microenvironment in vivo, promote CD31-mediated angiogenesis, and accelerate infected wound healing. Collectively, this work identifies DMBQ as a natural antimicrobial agent, and its combination with hydrogel microneedles offers an effective route for swift therapy of infected wounds.

Significance Dermal repair is a tightly regulated process that becomes progressively impaired with aging, chronic diseases, and persistent tissue injury. Senescent cells (SnCs) accrue in the skin following damage and with advancing age, contributing to alterations in tissue homeostasis and repair. However, the role of SnCs in normal and impaired wound repair is pleiotropic and context-dependent, particularly in the context of age and chronic disease. Furthermore, the use of senotherapeutics that target SnCs can slow aging, mitigate chronic disease, and promote rejuvenation of aged tissues, implicating their potential efficacy in reverting dysregulated wound repair. Recent advances The implementation of multi-OMIC analysis examining SnCs has improved our understanding of SnC heterogeneity within the skin and identified distinct SnC subsets that differentially influence tissue repair and its dysfunction. These studies have facilitated the development of senotherapeutics that selectively eliminate SnCs or suppress their detrimental phenotype. Preclinical studies demonstrate that treatment with senotherapeutics can improve tissue integrity and restore regenerative capacity. Critical issues Despite significant progress, the types, functions, and temporal dynamics of SnC populations involved in wound healing remain poorly characterized. Further molecular and functional SnC phenotyping, especially under aged and diseased conditions, will be required to distinguish beneficial reparative senescence from persistent pathogenic senescence. In addition, optimal therapeutic timing, specificity, and delivery strategies remain unresolved.[Figure: see text]Future Directions:Integrating multiomics approaches in preclinical and clinical studies will be required to distinguish beneficial transient senescence from persistent pathogenic senescence for the further development of SnC-targeting therapies.

Nitric oxide (NO) donor-based gas therapy has been widely explored to promote angiogenesis in diabetic wound treatment, particularly to compensate for insufficient endogenous NO levels in damaged tissues. Here, we present a skin-derived extracellular matrix (ECM)-based platform that leverages its inherent biocompatibility and cell affinity for efficient NO delivery. An NO donor was chemically grafted onto the ECM scaffold, which was subsequently processed into a hydrogel (H@ECM-SNO/Sal-B) capable of encapsulating salvianolic acid B (Sal B), a bioactive phytochemical with pro-healing potential. This dual-functional system is designed to enhance vascular regeneration and modulate inflammatory responses within the diabetic wound microenvironment. The resulting hydrogel exhibited favorable gelation properties and sustained release of both NO and Sal B. In vitro studies demonstrated that H@ECM-SNO/Sal-B significantly enhanced human umbilical vein endothelial cell proliferation, migration, and tube formation, indicating an enhanced pro-angiogenic effect of the combined formulation. In vivo , the hydrogel accelerated wound closure, reduced inflammatory infiltration, promoted epidermal regeneration, and enhanced collagen deposition. Furthermore, it markedly upregulated the expression of angiogenesis-related markers, including hypoxia-inducible factor-1α (HIF-1α) and CD31, confirming its ability to stimulate neovascularization. By leveraging ECM as a bioactive NO carrier, this hydrogel platform enables the combined delivery of NO and Sal B, providing a multifunctional strategy for promoting diabetic wound healing.

Skin wound healing remains a prominent clinical challenge, creating an urgent demand for high-performance wound-care biomaterials. Deaminotyrosine (DAT), a recently identified flavonoid-derived gut metabolite, exhibits anti-inflammatory and immunomodulatory activities. Nevertheless, its translational application is greatly restricted by poor aqueous solubility, insufficient stability, and potential dose-dependent toxicity. Herein, we fabricated a novel zirconium-based metal-organic framework carrier loaded with DAT (denoted DAT@Zr-MOF). The resulting nanocomposite displayed a uniform spherical morphology, favorable colloidal stability, and satisfactory drug loading capacity. In vitro experiments verified its desirable hemocompatibility and cytocompatibility. DAT@Zr-MOF could be efficiently internalized by HUVECs and markedly facilitate endothelial angiogenesis, proliferation, and migration. Additionally, it inhibited LPS-triggered NF-κB signaling activation, TNF-α secretion, and ROS accumulation in RAW264.7 macrophages. After integration into a thermosensitive poloxamer 407 hydrogel, DAT@Zr-MOF significantly accelerated wound closure in a murine full-thickness skin defect model. The formulation facilitated re-epithelialization, collagen deposition, and neovascularization, achieving superior therapeutic effects relative to the blank control and free DAT groups. RNA-seq profiling of day-15 wound tissues identified 549 differentially expressed genes (DEGs). Functional enrichment analyses indicated that these DEGs were closely associated with core biological events, including skin development, keratinocyte differentiation, cytokine-receptor interactions, and leukocyte migration. Protein-protein interaction network analysis further uncovered hub genes such as Krt84 , Ccl19 , and Csf2 . Collectively, the DAT@Zr-MOF composite hydrogel expedites cutaneous wound healing by synergistically modulating angiogenesis, inflammatory response and tissue remodeling through multi-path

Burn wound infections remain a major clinical challenge due to extensive tissue damage, delayed healing, and increased susceptibility to microbial contamination, which can limit the effectiveness of conventional topical formulations. This study aimed to develop and optimize a Quality-by-Design (QbD)-based non-propellant foam (NPF) containing silver nitrate, chlorhexidine, and asiaticoside for enhanced burn wound management. A sequential design of experiments strategy was employed, involving Taguchi L8 screening followed by Box-Behnken optimization to identify the critical formulation variables influencing foam performance and drug release. The optimized formulation exhibited desirable physicochemical characteristics, including a foam density of 0.192 ± 0.002 g/mL, a skin-compatible pH of 5.56 ± 0.04, uniform drug content (98-99%), and satisfactory foam stability. In-vitro studies demonstrated cumulative drug release of 94.69% chlorhexidine, 82.13% asiaticoside, and 78.63% silver nitrate within 6 h, with the release profiles predominantly following the Higuchi diffusion model. Accelerated stability studies indicated that the formulation remained stable over six months. In a Sprague-Dawley rat burn wound model, the optimized foam achieved 93.29 ± 1.75% wound contraction by day 14, outperforming both the untreated control and the marketed formulation. Furthermore, biochemical analyses revealed increased hydroxyproline, hexosamine, and hexuronic acid levels, while histopathological examination confirmed enhanced collagen deposition, neovascularization, and re-epithelialization. These findings demonstrate that the developed QbD-based non-propellant foam represents a promising preclinical topical delivery platform capable of supporting both antimicrobial protection and tissue repair during burn wound healing.

The aim of this research was to synthesise evaluative research on support surfaces in pressure ulcer care in nursing homes, by examining how studies address effectiveness, efficiency, user satisfaction and context of use. Following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines, six databases were used. Studies assessing support surfaces in nursing homes were included. Data extraction covered studies' characteristics, support surfaces evaluated and methodologies employed. Among the 68 included studies, 40 focused primarily on support surface evaluation, mainly assessing effectiveness or efficiency (n = 31, 78%) rather than context of use (n = 5, 12%) or user satisfaction (n = 4, 10%). Residents' perspectives were captured in 42.5% (n = 17) of studies and quality of life in 25% (n = 10), with one qualitative study identified. Mattresses predominated among the 188 support surfaces evaluated (47%, n = 88). Studies were concentrated among seven research teams (49%, n = 33), and industry funding was the most common source overall (37%, n = 25). Current research prioritises effectiveness and efficiency assessment over holistic usability assessment. The limited incorporation of residents' and professionals' experiences and quality of life outcomes reveals a gap between biomedical approaches and person-centred perspectives. Future research should place residents' and professionals' experiences at the centre of support surface evaluation to generate clinically relevant and ethically grounded evidence.

Chronic wounds remain a major healthcare challenge because persistent inflammation, biofilm formation, oxidative stress, protease imbalance, hypoxia, and impaired angiogenesis prevent progression through normal healing. Conventional wound dressings provide passive protection but cannot continuously monitor the dynamic wound microenvironment or deliver adaptive therapy. Unlike previous reviews that independently summarize wound biosensors, responsive biomaterials, or drug-delivery systems, this review critically integrates the complete closed-loop paradigm of intelligent wound management, from single- and multi-stimuli-responsive sensing to AI-assisted autonomous therapeutic intervention. Chemical and physical sensing modalities are comparatively evaluated based on analytical performance, selectivity, clinical readiness, and translational limitations, while multi-responsive logic-gated platforms are assessed against conventional single-stimulus systems. The review further synthesizes available human clinical evidence, compares fabrication strategies and manufacturing scalability, and discusses regulatory pathways governing combination products, Software as a Medical Device, and AI-enabled wound care. Particular emphasis is placed on AI model development, data quality, validation, bias mitigation, and cybersecurity requirements for safe clinical deployment. Finally, major barriers including material scalability, long-term biocompatibility, sensor robustness, standardized clinical validation, and regulatory governance are critically analyzed to establish a translational framework for developing clinically reliable, intelligent smart bandages capable of precision management of chronic wounds.

A novel gold nanoparticle-chitosan (AuNP@chitosan) composite is introduced as a potent biointerface modulator for burn trauma care. In this study, the unique interfacial characteristics of the composite are linked to its therapeutic activity, and its effects on endothelial function and immune response in severe bleeding and inflammatory models are examined. AuNP@chitosan synthesis was verified using FTIR and fluorescence, and its effects were assessed in TNF-α-induced HUVECs, LPS-stimulated macrophages, and an animal model. In vitro, AuNP@chitosan protects TNF-α-injured human endothelial cells (HUVECs) by restoring thrombomodulin expression, reducing ROS, and relieving the upregulated hypoxia-adaptive markers (HIF-1α and fibronectin). Concurrently, in LPS-stimulated RAW 264.7 macrophages, it suppresses pro-inflammatory mediators (TNF-α and IL-6) while preserving COX-1 and enhancing IL-10 production. These cell-specific responses reflect distinct but complementary mechanisms, vascular protection and immune regulation, which were further validated in a rat burn model. In vivo application of AuNP@chitosan dressings significantly reduced infiltration of CD4 + , CD8 + , and CD68 + immune cells in wound tissue, supporting the translational relevance of the dual in vitro findings. The integrated cell and animal studies demonstrate that AuNP@chitosan acts via redox and immune modulation to promote a pro-healing wound environment.

The versatility of electroresponsive hyaluronic acid (HA)-based hydrogels, a promising platforms for wound healing, can be further extended to controlled drug delivery, enabling on-demand release of therapeutic agents. This work reports the development of advanced HA-based electroresponsive hydrogels incorporating electrospun poly(lactic acid) (PLA) fiber mats functionalized with conducting polymers (CPs), such as poly(hydroxymethyl-3,4-ethylenedioxythiophene) and polypyrrole, and loaded with chloramphenicol (CAM). The systems were fabricated through a multi-step approach involving plasma treatment, in situ polymerization of CPs on the fiber mats, and then semi-interpenetration with CP within a click-chemistry crosslinked HA network. The resulting hybrid hydrogels exhibited suitable mechanical properties, swelling behavior, and electrochemical activity, enabling CAM release under both passive and controlled electrically stimulated conditions while maintaining biocompatibility. Electrical stimulation significantly enhanced the initial burst release, while the subsequent release phase showed a sustained profile over an extended period (11 days). The antibacterial activity of the released CAM was confirmed against E. coli and S. aureus using an agar diffusion assay. Although both CPs exhibited comparable CAM release behavior, the polypyrrole-based hydrogel demonstrated superior wound healing performance. Overall, these findings highlight the potential of electroresponsive HA-based composite hydrogels as smart wound dressings capable of controlled and sustained antibiotic delivery.