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Despite favourable outcomes of non-surgical endodontic retreatment (NS-ReTx), treatment decisions for previously treated posterior teeth with apical periodontitis remain inconsistent. This ambispective cohort study evaluated NS-ReTx outcomes in posterior teeth. Permanent posterior teeth undergoing NS-ReTx in a residency program (2010-2023) with ≥24-month follow-up or an untoward event were included; otherwise, recall was attempted. Teeth were classified as healed, healing, or diseased. Periapical healing was defined using strict and loose criteria, and event-free survival as time to reintervention or last event-free follow-up. Analyses used logistic regression and Kaplan-Meier methods (α = 0.05). Periapical healing analyses included 423 teeth (367 patients; median follow-up 3.7 years), comprising retrospectively (n=276; median follow-up 3.4 years) and prospectively (n=147; median follow-up 4.3 years) ascertained subgroups. Overall strict/loose periapical healing rates were 82.7%/89.8%, compared with 80.8%/87.0% and 86.4%/95.2% in the retrospective and prospective subgroups, respectively. Periapical healing rates were higher among teeth with longer follow-up. Absent or smaller preoperative periapical radiolucency (PARL) and adequate-quality final restorations were associated with improved strict periapical healing. Survival analyses included 480 teeth (417 patients). Kaplan-Meier estimated event-free survival was 96.5%, 94.5%, and 92.7% at 2, 4, and 6 years, respectively. The overall crude event-free survival rate was 93.3% with a median follow-up of 3.3 years. Contemporary NS-ReTx in posterior teeth showed high periapical healing and event-free survival. Absent or smaller PARL and adequate-quality final restorations were associated with improved periapical healing. These findings should be interpreted considering potential selection bias from incomplete long-term follow-up.

Delayed wound healing after open reduction and internal fixation (ORIF) of distal fibular fractures can impair recovery and increase infection risk. The purpose of this study was to develop a simple preoperative scoring system to predict delayed wound healing after plate fixation in patients with closed distal fibular fractures. This retrospective cohort study reviewed 84 patients who underwent plate fixation for closed distal fibular fractures between 2018 and 2024. Delayed wound healing was defined as a surgical wound rated as Grade 2 or higher according to the Southampton Wound Assessment Scale postoperatively. The following preoperative variables were collected, binarized, and entered into a logistic regression model to develop a weighted risk score: age, diabetes mellitus status, fracture characteristics, and planned number of plates. Delayed wound healing occurred in 30 patients. Multivariate analysis identified age ≥70 years, complex fracture type, and use of ≥2 plates as independent predictors of delayed wound healing. Presence of diabetes mellitus was retained for clinical relevance. Each predictor was weighted as follows: age and diabetes, one point each; fracture type and planned use of ≥2 plates, two points each. These scores demonstrated good predictive performance. We developed a simple preoperative scoring system for predicting delayed wound healing following ORIF for closed distal fibular fractures using four clinical variables, supporting early risk stratification. This model may aid in identifying high-risk patients preoperatively, allowing for informed surgical planning and individualized perioperative care to minimize wound complications.

Plantago (Plantaginaceae family) exhibits remarkable diversity with over 200 species. These plants are closely associated with traditional medicine worldwide, particularly as a wound healing therapy. Recent research has revealed phytoconstituents in various Plantago species, including flavonoids, alkaloids, terpenoids, phenolic acid derivatives, iridoid glycosides, fatty acids, and polysaccharides. Despite the advanced ongoing research on Plantago extracts, there is still a gap in the evaluation of their potential as an effective topical product for chronic wounds and in the way phytoconstituents contribute to the overall effect in a single comprehensive systematic review. Therefore, this review aims to explore the wound healing capabilities of Plantago and its phytoconstituents, as well as elucidate their mechanisms of action. Our analysis emphasizes the significant wound healing potential in 25 Plantago species, notably Plantago major, Plantago lanceolata, Plantago australis, Plantago asiatica, and Plantago ovata. These plant species contain a diverse array of 57 phytoconstituents that collectively contribute to these activities. In conclusion, this review confirms the huge potential of Plantago genus as a topical wound healing agent. The healing mechanisms cover a wide array of effects such as anti-bacterial activity, anti-apoptosis, stimulation of collagen synthesis and deposition, promotion of angiogenesis, suppression of inflammatory response, inhibition of cyclooxygenase, inhibition of MAPKs phosphorylation, and enhancement of endogenous antioxidant enzyme activity. A study on the network pharmacology of such potential is worth investigating as further research.

To compare the clinical efficacy of microwave in situ ablation (MWA) combined with intralesional curettage versus intralesional curettage alone for locally aggressive benign bone tumors, including giant cell tumor of bone, aneurysmal bone cyst, and chondroblastoma, with a focus on local recurrence control, limb function, and bone healing. This retrospective cohort study included 284 patients who were divided into a combined group (MWA plus curettage, n=156) and a control group (curettage alone, n=128). Baseline characteristics, perioperative outcomes, complications, local recurrence, bone healing status, and Musculoskeletal Tumor Society (MSTS) scores were compared. Recurrence-free survival (RFS) was analyzed using Kaplan-Meier method, and independent risk factors were evaluated using Cox regression analysis. Subgroup analyses were performed based on pathologic type and lesion size. The combined group had a significantly lower local recurrence rate than the control group (7.1% vs. 18.0%, P=0.008) and an improved RFS HR=0.38, 95% CI: 0.19-0.79). MSTS scores were significantly higher in the combined group at all postoperative time points (all P>0.05). Bone healing time was shorter in the combined group (4.3&#xb1;1.5 vs. 5.0&#xb1;1.5 months, P<0.001), with a lower rate of delayed union (5.8% vs. 18.8%, P=0.001). Multivariable analysis identified MWA as an independent protective factor (HR=0.25, P<0.001), while soft tissue involvement, lesion diameter >6 cm, and extensive cortical destruction were independent risk factors. Subgroup analyses showed consistent benefits in larger lesions. MWA combined with intralesional curettage significantly reduces local recurrence, improves limb function, and accelerates bone healing compared to curettage alone. It represents a safe and effective limb-salvage strategy for locally aggressive benign bone tumors.

Corrosion resistance and self-healing capabilities of epoxy coatings that have been enhanced with cellulose nanofiber (CNF)-loaded ammonium molybdate (NH4)2MoO4 and applied to mild steel substrates were investigated in this work. Additive concentrations 1, 2.5, and 5 wt% were added to the coating system to investigate the electrochemical behavior and healing efficiency in a 3.5% NaCl environment at room temperature. Electrochemical measurements, including open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization, revealed that increasing additive concentration resulted in a significant improvement in corrosion resistance. The results showed a considerable decrease in corrosion current density and corrosion rate, as well as an increase in polarization resistance, with the 5% addition sample having the greatest value. Anodic and cathodic processes were both reduced by the inhibitor-modified coatings' mixed inhibitory behavior. The electrochemical results were validated by optical microscope analysis, which showed decreased corrosion damage and the development of a compact protective layer at scratched locations, especially in samples containing 2.5% and 5% additive. With the 5% addition system, the self-healing efficiency rose to 97.80% from 91.92% for the clean epoxy coating. The findings show that the CNF-molybdate system controls inhibitor release and creates a protective barrier in situ, greatly increasing corrosion resistance and durability in harsh settings, making it a good self-healing coating.

Diabetic wounds, a common and serious complication of diabetes, are characterized by delayed healing, primarily due to excessive accumulation of reactive oxygen species (ROS) and heightened vulnerability to bacterial infection. Herein, to address the urgent need for effective wound healing materials, we developed a thermoresponsive therapeutic hydrogel composite comprising bilirubin-loaded mesoporous polydopamine nanoparticles (BR@mPDA NPs) incorporated into an alginate/Pluronic F127 (A/F) hydrogel matrix. Upon near-infrared (NIR) laser irradiation, mPDA NPs generated a photothermal effect that eradicated more than 90% of bacteria and triggered the controlled release of BR. Furthermore, the A/F hydrogel demonstrated superior biocompatibility by maintaining cell viability above 85% and exhibited favorable hemocompatibility due to the presence of alginate. The incorporation of BR facilitated the polarization of pro-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype, thereby accelerating wound healing. In vitro experiments demonstrated that the BR@mPDA-A/F hydrogel reduced intracellular ROS levels by approximately 40%, indicating effective ROS scavenging activity. In vivo evaluation also represented significantly accelerated diabetic wound healing, achieving 90.2% wound closure by day 7 compared with 66.4% in the control group, accompanied by enhanced tissue regeneration and no detectable toxicity. Collectively, these findings highlight the BR@mPDA-A/F hydrogel as a promising therapeutic platform for diabetic wound management.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for perioperative analgesia, but effect on bone healing remains controversial. This umbrella review and reconstructed meta-analysis assessed whether NSAIDs impair bone healing and how risk varies by population, fracture type, dose, and duration. We conducted an umbrella review of systematic reviews/meta-analyses and a reconstructed meta-analysis of primary studies (PRIOR/PRISMA-compliant; PubMed, EMBASE, Web of Science, and Scopus to 9 November 2025). Two reviewers independently screened, extracted, and assessed quality (AMSTAR-2) and risk of bias. Overlapping cohorts were removed, and random-effects models were applied. Prespecified subgroups included age, clinical context (traumatic vs elective procedures), bone type (long bones vs spine), dose, and exposure duration (&#x2264;14 days). Sixteen reviews (10 meta-analyses, six systematic reviews) were included; most suggested that NSAIDs increase impaired bone healing risk, particularly with higher doses or prolonged use, with minimal signal for short, low-dose perioperative regimens, especially in spinal fusion. Quality was low/critically low. The meta-analysis pooled 38 primary studies. NSAID exposure was associated with higher nonunion risk (OR, 1.56, 95% CI, 1.18 to 2.11), but not clearly with delayed union (OR, 1.58, 95% CI, 0.65 to 3.67). Risk increased in adults (OR, 1.67, 95% CI, 1.25 to 2.47) but not in pediatric patients (OR 0.77, 95% CI 0.58 to 1.02), was higher in long-bone fractures than in spinal fusion, trended upward with higher doses, and was not elevated with short-term (&#x2264;14 days) use. Risk also differed by clinical context, higher in traumatic versus elective procedures. NSAID-related impairment of bone healing seems dose and context-dependent, with clinically important risk particularly in adults, long-bone fractures, and higher dose regimens. Short-term use (&#x2264;14 days) was not associated with increased nonunion risk. Risk seemed higher in traumatic fractures than in elective procedures. These findings support caution in higher risk scenarios, suggesting that short-duration NSAID use may be safe when avoiding higher dose exposure.

Diabetic wound is marked by chronic inflammation, oxidative stress, and poor tissue regeneration, requiring novel wound dressings. In this work, electrospun nanofibers of polyacrylonitrile (PAN) loaded with apigenin and naringenin as an effective strategy to promote diabetic wound healing have been developed. Characterization of the optimized nanofibers was performed using physicochemical, mechanical, surface, and biological methods, after which the wound healing activity of the nanofibers in a diabetic wound model induced by streptozotocin and nicotinamide was evaluated. The prepared nanofibers demonstrated a smooth structure, high content of drugs (91.2&#x202f;&#xb1;&#x202f;3.4% apigenin, 87.6&#x202f;&#xb1;&#x202f;2.8% naringenin), good mechanical stability, increased hydrophilicity (58.4&#x202f;&#xb1;&#x202f;2.1&#xb0;), biphasic drug release pattern, high biocompatibility, and antioxidant properties. In vivo experiments revealed that the nanofibers accelerate wound healing and lead to wound closure of 96.47&#x202f;&#xb1;&#x202f;3.23% on day 14 along with enhanced epithelialization, collagen synthesis, and inhibition of NF-&#x3ba;B and TNF-&#x3b1; expression.

Oxidative stress and immune microenvironment dysregulation are key pathological mechanisms underlying impaired wound healing, particularly in chronic non-healing wounds such as diabetic ulcers. Developing dressings that synergistically scavenge reactive oxygen species (ROS) while correcting aberrant immune responses is therefore of significant clinical value. Electrospun nanofibers, due to their high specific surface area and ECM-mimicking porous architecture, are promising candidates for wound repair. In this study, a biocompatible, biodegradable core-shell nanofiber scaffold (PCL-GA/SF, PGS) was fabricated via coaxial electrospinning, with a polycaprolactone (PCL) core loaded with glabridin (GA) and a silk fibroin (SF) shell. PGS exhibited a uniform, interconnected network morphology with an average diameter of 433 &#xb1; 264 nm, a tensile strength of 1.82 &#xb1; 0.13 MPa, and a water contact angle of 48.1&#xb0; &#xb1; 14.2&#xb0;, which was favorable for wound healing. In vitro, PGS significantly promoted L929 fibroblast adhesion and proliferation, effectively scavenged ROS, and attenuated H2O2-induced oxidative cytotoxicity. Mechanistically, PGS remodeled the local microenvironment by driving macrophage polarization from the pro-inflammatory M1 phenotype to the pro-regenerative M2 phenotype, synergistically enhancing fibroblast function. In vivo, PGS scaffolds markedly accelerated skin tissue reconstruction and promoted regeneration of cutaneous appendages, including hair follicles and sweat glands. In conclusion, through rational core-shell design, this study integrates antioxidant and immunomodulatory functions within a single coaxially electrospun scaffold, offering a clinically translatable strategy for chronic diabetic wound repair and the comprehensive structural and functional reconstruction of skin tissue.

Wound management faces several critical challenges, including infection, delayed healing, and pain. To address the issues, we developed a multifunctional film by loading bupivacaine into a PVA-TCN-polydopamine electrospun membrane (PVA/TCN@DA-BL), offering a new strategy for wound analgesia and infection control. Chitin nanofibers (TCN), a natural bioactive component, synergistically enhanced the membrane's antibacterial efficacy, structural stability, and overall wound healing capacity. In vitro evaluations confirmed excellent biocompatibility, with cell viability exceeding 95% in both mouse embryonic fibroblasts and macrophages, and hemolysis rates below 1.5%. In a murine wound model, the PVA/TCN@DA-BL groups achieved nearly complete wound closure by day 11, significantly outperforming the control group. Histological analysis revealed accelerated re-epithelialization, dense collagen deposition, and well-organized granulation tissue formation. Immunofluorescence staining showed increased phosphorylation levels of mTOR and p70S6K in the treated wounds, suggesting that REDD1/mTOR-related signaling changes may be associated with the overall wound-repair microenvironment. The work suggests that the PVA/TCN@DA-BL not only provides analgesic effects but also actively promotes cellular proliferation and tissue regeneration through molecular pathway modulation. The electrospun membranes combine structural stability, biocompatibility, and bioactive healing acceleration, showing significant potential for clinical wound management applications.

Uncontrolled non-compressible visceral hemorrhage and irregular wet wounds remain difficult to manage because many hemostatic powders lack robust wet adhesion and mechanical integrity under continuous blood flow, leading to displacement and rebleeding. Here, a multifunctional, natural-polysaccharide hemostatic powder (CSO) is engineered from carboxymethyl chitosan (CMCS), dopamine-grafted sodium alginate (SA-DA), and oxidized guar gum (OGM), and the mixture is activated by EDC/NHS to enable rapid, in situ self-crosslinking. Upon contact with wound, the CSO powder rapidly absorbs tissue exudate or blood, concentrates coagulation factors and blood cells, and undergoes in situ self-crosslinking to form a stable, adherent hydrogel that seals the wound for rapid hemostasis. The incorporated dopamine moiety endows the hydrogel with potent free radical scavenging ability, effectively mitigating oxidative stress and inflammation to accelerate wound healing. In addition, the CSO powder exhibits notable antimicrobial activity, helping to prevent post-hemostatic infection. In rat tail-amputation and liver-incision models, CSO achieves rapid hemostasis with markedly reduced blood loss, and further accelerates infected full-thickness skin repair by dampening inflammation and improving collagen remodeling. These features, together with favorable biocompatibility and practical applicability, position CSO as a promising powder-to-hydrogel platform for emergency and surgical hemostasis with improved healing outcomes.

To evaluate the effect of ultrasound-guided high ankle block (HAB) on postoperative wound healing and foot perfusion after diabetic foot debridement. This prospective, assessor-blinded randomized controlled trial (NCT06395961) enrolled 70 patients with Wagner II-IV diabetic foot ulcers undergoing debridement. Thirty-five patients received HAB with 35 mL of 0.375% ropivacaine, and 35 received general anesthesia (GA). The primary outcome was ulcer area on postoperative day 7, measured using ImageJ boundary delineation. Ulcer area was also assessed on days 1, 7, 14, 28, and 60. Secondary outcomes included: anterior and posterior tibial artery hemodynamics assessed by Doppler ultrasound on days 1, 7, and 14; foot skin temperature measured by infrared thermography on days 2, 4, 6, 8, 10, 12, and 14 (to avoid interference with ultrasound measurement); and visual analog scale (VAS) pain scores, opioid consumption, and adverse events assessed at various time points. The HAB group showed significantly higher ulcer healing rates on day 7 (42.2% vs. 29.4%, P=0.04), day 14 (67.9% vs. 53.2%, P=0.02), day 28 (85.7% vs. 75.2%, P=0.02), and day 60 (96.8% vs. 91.2%, P=0.01). Arterial flow volume, peak systolic velocity, end diastolic velocity, time-averaged mean velocity, and time-averaged maximum velocity were significantly improved in the HAB group on days 1 and 7 (all P<0.001). The HAB group also had significantly higher foot skin temperatures (P<0.05), lower VAS scores (P<0.001), and lower opioid consumption (P<0.001). Pneumonia occurred less frequently with HAB (2.9% vs. 20.0%, P=0.055). No significant differences were observed in reoperation or amputation rates. HAB enhances foot perfusion, accelerates early ulcer healing, and provides superior analgesia with fewer complications compared with GA.

Diabetic wounds struggle to self-heal due to excessive accumulation of reactive oxygen species (ROS), persistent microbial infection, and ineffective exudate management. Current wound dressings remain inadequate for effectively modulating this complex pathophysiological microenvironment. Herein, using cotton-derived cellulose and hyaluronic acid as raw materials, we developed a dual-crosslinked hydrogel through a facile and rapid photo-crosslinking process (<10&#xa0;s), allowing it to be molded into any desired shape to fit irregular wounds. Benefiting from a dynamic and robust dual-crosslinked network, the resulting hydrogel exhibits autonomous self-healing capability, and strong tissue adhesion, making it adaptable to complex wound environments. Notably, owing to the incorporation of quaternized and dopamine groups, it demonstrates a 99% antibacterial rate in vitro and achieves 90% clearance efficiency of ROS in vivo. Furthermore, this design confers the hydrogel with efficient coagulation-promoting and hemostatic capabilities. In type II diabetic wounds, the hydrogel can achieve 100% closure by day 14, and the histological staining revealed enhanced tissue regeneration and orderly collagen deposition. This work presents a promising polysaccharide-based hydrogel with synergistic multifunctionality serving as a versatile therapeutic candidate for the effective management and healing of diabetic wounds.

This study aimed to develop and evaluate poly(vinyl alcohol)/gelatin (PVA/Gel/AgNPs) composite films containing silver nanoparticles (AgNPs), which have the potential to be used as burn wound dressings. In the present study, AgNPs at different concentration were fabricated by a green hyrodthermel method with the help of functional groups of gelatin and PVA in the mixture of these polymers. Then, PVA/Gel composite surfaces containing in situ synthesized AgNPs were obtained in a simple and single step with solvent casting method. The chemical composition of the films was confirmed by Fourier-transform infrared spectroscopy (FTIR), verifying the presence of both gelatin and PVA. Morphological and elemental analyses performed by field emission scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDS) revealed a heterogeneous structure in AgNP-containing films, with uniformly distributed nanoparticles and characteristic silver peaks. X-ray diffraction (XRD) further confirmed AgNP incorporation, while thermogravimetric analysis (TGA) indicated enhanced thermal stability with increased residual mass at 900 &#xb0;C. Physicochemical evaluations demonstrated that the films were hydrophilic, exhibited high water retention capacity, and enabled sustained release of AgNPs. Additionally, AgNP incorporation improved the mechanical properties of the films. The AgNP-containing films exhibited concentration-dependent antibacterial activity, and formulations containing 5 and 10 mM AgNPs achieved complete bacterial growth inhibition (100%) against both Escherichia coli and Staphylococcus aureus. Cytotoxicity analysis performed using the MTT assay on L929 fibroblast cells confirmed that all films were non-toxic. The results obtained provide preliminary evidence of cytocompatibility. In vivo studies using third-degree burn wounds on Sprague-Dawley rats demonstrated effective wound healing over 21 days compared to commercial dressings. Overall, the developed PVA/Gel/AgNPs films exhibit strong potential as antibacterial wound dressings, with advantages including biocompatibility, ease of fabrication, and suitability for large-scale production.

The recalcitrant nature of chronic diabetic wounds stems from a complex pathological microenvironment characterized by bacterial biofilm formation, elevated reactive oxygen species (ROS) levels, and persistent inflammation. To address this challenge, we developed an L-arginine/ferrocene dual-functionalized chitosan hydrogel architecture (CLF@MZ) integrated with Ti3C2 MXene quantum dots (QDs) and ZIF-8 nanoparticles. This system aims to remodel the wound microenvironment through a multi-synergistic photothermal-biochemical strategy. Upon near-infrared irradiation, the MXene QDs generate localized hyperthermia to physically eradicate Staphylococcus aureus biofilms. Targeting the pathological microenvironment, CLF@MZ exhibits pH/ROS dual-responsive characteristics. In the acidic environment, ZIF-8 decomposes to release Zn2+; meanwhile, excessive ROS at the wound site is utilized to drive ferrocene-mediated conversion of L-arginine into NO. This cascade reaction not only consumes endogenous ROS to alleviate oxidative stress but also leverages the synergistic effects of the generated NO and Zn2+ to induce macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype. Subsequently, the anti-inflammatory microenvironment significantly promotes the neoformation of a mature vascular network and drives ordered collagen deposition. This synergistic system effectively overcomes the healing barriers of chronic diabetic wounds and achieves high-quality skin tissue repair, offering a novel microenvironment remodeling strategy for the treatment of complex chronic wounds.

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