Triclosan exposure perturbs skin lipid metabolism and inflammatory pathways: Insights from network toxicology and multi-omics analyses.

Forsythia suspensa accelerates wound healing by inhibiting neutrophil extracellular traps and activating Wnt/β-catenin via forsythoside A.

Lipoteichoic acid as a key wound healing mediator in Gram-positive bacteria.

Injectable photo-crosslinked hyaluronic acid/carboxymethyl cellulose hydrogel for the sustained delivery of rhFGF2 and accelerated wound healing.

Echinacoside improves antioxidant responses and angiogenesis through Parkin-MFN2-mediated mitophagy to promote diabetic wound healing.

Clinical translation of adipose-derived stem cell (ADSC)-derived extracellular vesicles (EVs) for cutaneous regeneration is challenged by variable secretion levels, heterogeneous molecular cargo, and inconsistent therapeutic potency. Here, we developed a mechanically tunable and biomolecularly instructive photocurable hybrid hydrogel (GelMA/HAMA/PEGDA) that serves both as a 3D culture microenvironment for ADSCs and as an EV-delivery scaffold. Systematic screening of PEGDA-controlled crosslinking identified GH11P (97% [15% GelMA : 1% HAMA = 1 : 1 (v/v)] + 3% PEGDA) as a formulation with balanced stiffness, controlled degradation, and cytocompatibility, supporting EV production under 3D culture. Multi-omics profiling suggested that EVs produced in this 3D matrix (3D-hcEVs) exhibit regenerative-associated signatures, including ECM-integrin interactions, focal adhesion-related pathways, PI3K-AKT signaling, and a keratin-enriched proteomic signature compared with dish-cultured EVs (dcEVs). Additional in vitro validation showed that 3D-hcEVs enhanced HaCaT migration and more strongly increased p-AKT/AKT than dcEVs at 30 and 60 min. An NTA-based in vitro release assay further demonstrated partial, sustained EV release from GH11P over 7 days. In a full-thickness dorsal wound model, GH11P scaffolds loaded with 3D-hcEVs accelerated wound closure compared with dcEV-loaded scaffolds and hydrogel-only controls. Histological analyses further indicated improved tissue regeneration features, including enhanced re-epithelialization, epidermal stratification, collagen organization, increased CD31+ neovascularization, and reduced CD68+ macrophage infiltration. Collectively, these results support the feasibility of a tunable hydrogel platform that integrates mechanical and biomolecular microenvironmental cues to modulate EV-associated molecular signatures and evaluate EV delivery for cutaneous wound repair.

Autologous vein grafting is commonly used for traumatic limb arterial defects when tension-free primary repair is not possible. The no-touch harvest technique has shown structural and patency advantages in coronary surgery, but its role in traumatic upper-extremity reconstruction remains uncertain. A 63-year-old man sustained an open right elbow injury caused by a fan blade, with brachial artery transection, superficial venous injury, lateral antebrachial cutaneous nerve injury, and superficial brachioradialis laceration. After microscopic debridement, the arterial defect between viable ends measured about 5.5cm. A median cubital vein within the wound was selected as an interposition conduit because an adequate segment remained outside the most severely damaged zone, the wall appeared continuous without visible thrombosis or crush injury, and the caliber matched the brachial artery. The vein was harvested with a limited cuff of surrounding tissue using a no-touch concept, reversed, and anastomosed end-to-end under the microscope. The patient received intraoperative heparin and short-term postoperative low-molecular-weight heparin, but no long-term oral antithrombotic therapy because of individualized bleeding-risk and wound considerations. At 20 months, duplex ultrasonography and computed tomography angiography showed sustained graft patency, preserved distal runoff, and mild ectatic change without hemodynamically significant stenosis, occlusion, or pseudoaneurysm. This case supports technical feasibility rather than superiority in selected traumatic brachial artery injuries. An in-wound superficial vein may be usable when a structurally intact segment remains available outside the most severely injured zone. The no-touch concept was technically applicable in this setting, but its clinical benefit in peripheral trauma remains unproven.

Multidrug-resistant (MDR) bacterial infections and persistent oxidative stress exert a prolonged, hostile inflammatory pressure in chronic skin wounds, posing a formidable clinical challenge. Current antibiotic-based modalities often fall short in inflammation resolution and cutaneous regeneration. Here, we present the design of a reactive oxygen species (ROS)-balancing MXene/MoSe2 (MX/Mo), with MoSe2 synthesized on MXene surfaces via a solvothermal method. In infections, MX/Mo under ultrasound activation promotes efficient electron-hole separation to trigger a localized ROS storm. This disturbs the bacterial respiratory chain and irreversibly blocks adenosine triphosphate synthesis, causing lethal energy deprivation and MDR bacterial eradication. During healing, MX/Mo without ultrasound exhibits significant multienzyme-like activity to autonomously scavenge residual ROS, alleviating oxidative injury. In in vivo studies, MX/Mo exhibits superior antibacterial and wound healing efficacy by rapidly suppressing severe Methicillin-resistant Staphylococcus aureus infections and creating a favorable microenvironment with balanced ROS levels, thereby triggering angiogenesis and promoting collagen deposition for tissue regeneration. We anticipate that MX/Mo addresses skin wounds with multifactorial pathologies by integrating antibacterial activity and oxidative stress regulation, which offers new possibilities for treating a broad range of bacterial infection-driven disorders.

Management of unstable anterior pelvic ring fractures has shifted toward minimally invasive fixation techniques. This prospective randomized cohort study compares anterior subcutaneous internal fixator with percutaneous retrograde pubic ramus screw fixation, evaluating radiological outcomes, functional scores, complications, and peri-operative parameters. Fifty adult patients with unstable anterior pelvic ring injuries (Tile B & C; Young-Burgess lateral compression and vertical shear mechanisms) were enrolled between 2023 and 2025 and randomized into two equal groups: group 1 (internal fixator) and group 2 (retrograde pubic screw). Both groups underwent individualized posterior ring fixation as required. Outcomes assessed included operative time, blood loss, fluoroscopy time, union rate, Matta radiological score at 6 months, Majeed and Pelvic Outcome Scores at 12 months, and post-operative complications. Management of anterior pelvic injury showed that retrograde screw fixation demonstrated significantly shorter operative time (32.0 ± 9.2 vs. 50.3 ± 8.4min, p < 0.001) and less intraoperative blood loss (68.3 ± 16.2 vs. 122.3 ± 31.8ml, p < 0.001). Radiological outcomes were comparable: excellent Matta score in 68% vs. 64% (p = 0.834). Union time showed no significant difference (14.1 ± 2.4 vs. 15.1 ± 1.5 weeks, p = 0.076). Functional outcomes at 12 months showed no significant difference in Majeed score (p = 0.517), while Pelvic Outcome Score favored the retrograde screw group (32.3 ± 3.5 vs. 30.0 ± 3.3, p = 0.023). Internal fixator had a higher rate of lateral femoral cutaneous nerve injury (28%), while retrograde screw fixation showed fewer reoperations and lower implant removal rate. Upon reviewing study cases and relevant literature, both minimally invasive techniques can provide reliable fixation and comparable radiological and functional outcomes for unstable anterior pelvic ring fractures. Retrograde pubic ramus screw fixation offers advantages of reduced blood loss and lower neurovascular complications. Internal fixator offers slightly reduced fluoroscopy exposure but carries a higher risk of lateral femoral cutaneous nerve irritation. Level 4.

The pleural microenvironment has long been considered a passive anatomical boundary. However, emerging evidence identifies it as an active regulator of inflammation, tissue repair, and fibrotic remodeling. This review evaluates the mechanistic contribution of pleural mesothelial cells (PMCs) to pulmonary injury and fibrosis and explores their potential role in coordinating regenerative responses. Recent preclinical and clinical studies investigating pleural biology, mesothelial plasticity, mesothelial-mesenchymal transition (MesoMT), and pulmonary fibrosis were critically analyzed. Evidence from cutaneous wound healing was integrated to identify common molecular pathways governing tissue repair and fibrotic progression RESULTS: PMCs actively participate in pulmonary remodeling by secreting cytokines, growth factors, and extracellular matrix regulators. Persistent activation of TGF-β/Smad, Wnt/β-catenin, PI3K/Akt, and IL-6/STAT3 signaling promotes MesoMT, myofibroblast accumulation, and progressive extracellular matrix deposition in pulmonary fibrosis. Conversely, pleural-derived mediators have demonstrated regenerative potential by enhancing epithelial proliferation, migration, angiogenesis, and tissue repair in experimental models. Collectively, current evidence suggests that pleural signaling functions as a context-dependent regulatory network that influences the transition between effective regeneration and pathological fibrosis CONCLUSION: The pleura can be regarded as a dynamic signaling niche that extends beyond its traditional structural role. We propose the pleural microenvironment as a regulatory interface governing the balance between tissue regeneration and fibrotic remodeling. Targeting pleural-derived signaling networks may provide novel therapeutic opportunities for restoring physiological repair while limiting fibrotic progression in chronic lung diseases.

Skin wound healing involves a complex process hindered by limited cellular regeneration capacity, persistent inflammation, and insufficient angiogenesis. Epidermal growth factor (EGF) is a natural signaling molecule that promotes proliferation and migration at multiple stages of wound healing and tissue repair. However, rapid proteolytic degradation and instability within the harsh wound microenvironment constrain its bioavailability and therapeutic efficacy. In this study, an innovative recombinant EGF-loaded thermoresponsive nanocomposite hydrogel (EGF-LPs@PF127) was developed for multimodal wound healing management to enhance the effectiveness of growth factor therapy. This multifunctional hydrogel integrates EGF-loaded liposome as a nanocomposite to shield it from enzymatic breakdown and triblock copolymer Pluronic F-127 (PF127) as the thermoresponsive component for self-adapting dressings. With efficient encapsulation and sustained release of EGF, the multifunctional hydrogel demonstrates a remarkable ability to promote the proliferation and migration of keratinocytes and reduce the proinflammatory factor levels in macrophages. Furthermore, EGF-LPs@PF127 hydrogel administered locally undergoes in situ gelation at body temperature to adapt to wound shapes in a mouse full-thickness skin wound model. The EGF-functionalized nanocomposite hydrogel administration restores the epidermal integrity, reduces proinflammatory factors, and facilitates collagen deposition and angiogenesis, ultimately accelerating wound repair. This work underscores the efficacy of the nanoarchitecture-integrated hydrogel as a superior platform for growth factor delivery, holding considerable promise for enhancing tissue regeneration and wound healing management.

Selenium nanoparticle-and quercetin-embedded nanofibrous mats for enhanced cutaneous wound healing.

ABSTRACTScalp follicular unit (FU) transplantation is a highly effective yet underutilised minimally invasive technique for promoting healing in chronic and recalcitrant cutaneous wounds. In this case series, five patients with long‐standing nonhealing leg ulcers of mixed etiologies were treated exclusively with single FU grafts harvested from the scalp with a 0.9–1‐mm punch. Complete re‐epithelialization occurred in three cases by 6, 3 and 1 month, respectively, while the remaining two cases showed marked partial improvement at 6 months, with reduction in ulcer area and pain. Overall, all five patients experienced a favourable clinical outcome. Case reports suggest that the transplantation of a minimum of 4 FU grafts/cm2 is required to promote effective wound closure, with higher graft densities being associated with faster healing. However, the optimal graft density and placement, whether uniform distribution or targeting the wound edge to exploit an ‘edge effect’, require further investigation. Considered alongside prior reports, these results suggest that 1‐mm single‐FU grafting achieves wound healing comparable to, and often faster than, 2–3‐mm punch grafts. Additionally, the technique is less invasive and causes less bleeding, overall supporting wider use as an adjunct in multidisciplinary wound care.Level of Evidence: IV

Laminin-332 is a key extracellular matrix (ECM) protein that supports keratinocyte adhesion, migration, and re-epithelialisation during wound healing. Its loss, as in Junctional Epidermolysis Bullosa (JEB) disrupts re-epithelialization, which highlights its therapeutic relevance. However, direct application of full-length laminin or its fragments is limited by poor stability and high production costs. As an alternative, biomaterial scaffolds are being developed. The Capsular Antigen F1 (Caf1) is one such scaffold, offering a stable, customisable platform for presenting bioactive motifs in a more practical format. To develop stable Caf1 scaffolds displaying laminin-332 motifs and evaluate their therapeutic potential in promoting epithelial repair under both normal and laminin-deficient conditions, with the goal of enabling clinically translatable wound-healing strategies. Laminin-332-derived peptide motifs were identified through a systematic literature review and ranked using a scoring system. Leading candidates were engineered into Caf1 and expressed in Escherichia coli. Keratinocyte migration, motility, adhesion and pSMAD2 signalling were assessed in vitro using normal human epidermal keratinocytes and LAMA3-knockdown cells cultured on Caf1-coated plates. An ex vivo human skin wound model was used to assess translational relevance: wounded skin explants were treated with Caf1 constructs and cultured at the air-liquid interface for 7 days. Re-epithelialization and epithelial thickness were evaluated by haematoxylin and eosin staining. Caf1 proteins displaying laminin-332-derived motifs were expressed in E. coli and purified. Among the engineered constructs, Caf1-J3 and Caf1-J4 significantly enhanced keratinocyte migration and single-cell motility in vitro. Combined application further accelerated wound closure, suggesting complementary effects. In LAMA3-deficient keratinocytes, these coatings restored adhesion, promoted actin cytoskeletal organisation, and reduced nuclear pSMAD2 levels. In ex vivo wounded human skin, they also promoted re-epithelialisation and supported homogeneous neo-epidermis formation. These findings show that short laminin-332-derived motifs, when presented on the Caf1 scaffold, can mimic and partially recover key basement membrane functions in epithelial repair. Caf1-J3 and Caf1-J4 function as minimal bioactive units that restore keratinocyte cell adhesion and modulate key signalling pathways involved in wound healing. This modular protein platform offers a clinically relevant strategy for chronic wounds and ECM-deficient skin, and provides a foundation for next-generation regenerative therapies.

Exosomes from adipose-derived stem cells preconditioned with 650- or 810-nm photobiomodulation enhance cutaneous wound healing in rats.

Cyathula officinalis Kuan, a medicinal plant used in traditional medicine, remains underexplored as a source of structurally defined wound-repair polysaccharides. In this study, a water-soluble polysaccharide fraction, CoPS, was isolated from C. officinalis roots and structurally characterized using methylation analysis and 1D/2D NMR spectroscopy. Purified CoPS had a total carbohydrate content of 94.8%, a weight-average molecular weight (Mw) of 7.491 kDa, and a narrow dispersity (Mw/Mn = 1.04). Monosaccharide composition analysis showed that CoPS was mainly composed of fructose and glucose at a molar ratio of 95.60:4.40. Structural analyses identified CoPS as a branched levan-type fructan with a β-(2→6)-linked fructofuranosyl backbone and β-(2→1)-linked branching motifs. CoPS was incorporated into a Carbomer/alginate topical formulation, termed CoPS-CPG, and evaluated in vitro and in vivo. CoPS-CPG showed good cytocompatibility and promoted HaCaT keratinocyte migration, reducing the residual scratch area to 48.10% at 12 h compared with 70.13% in the control group and 65.18% in the vehicle (Blank-CPG) group. In a murine full-thickness excisional wound model, CoPS-CPG reduced the residual wound area to 8.70 ± 1.20% on day 14, compared with 24.83 ± 1.51% in the control group and 14.20 ± 0.72% in the vehicle group. Histological and immunological analyses further indicated improved tissue reconstruction, a reduced inflammatory burden, enhanced CD206-associated macrophage signals, increased CD31-associated vascular structures, improved α-SMA-associated perivascular coverage, and lower late-stage HIF-1α expression. These findings identify CoPS as a structurally defined plant-derived levan-type fructan that supports cutaneous wound repair.

Wound healing is a complicated process, so it’s critical to identify efficient ways to hasten recovery. Platelet-rich plasma (PRP) and zinc oxide nanoparticles (ZnO NPs) have demonstrated potential in improving cutaneous wound healing in a variety of species. But little is known about their combined effects, especially in dogs. Therefore, this study determined how topical infiltration of PRP and ZnO NPs ointment, both separately and in combination, affect the healing of dogs’ cutaneous wounds. Thirty-six full skin wounds were induced in the chest of six adult mongrel dogs. These wounds were randomly divided into six equal groups (6 wounds each) according to treatment protocol: group 1 served as a control and the wounds were dressed daily with normal saline only, group 2: the wounds were dressed daily with lanolin only, group 3: the wounds were infiltrated once with PRP, group 4: the wounds were treated with PRP single infiltration combined with lanolin ointment daily dressing, group 5: the wounds were dressed daily with ZnO NPs ointment, and group 6: the wounds were infiltrated once with PRP and daily dressed with ZnO NPs ointment. Wound healing progress was monitored; epithelialization, wound contraction, and overall healing were assessed. Total antioxidant capacity (TAC), malondialdehyde (MDA) and the concentration of platelets derived growth factor beta (PDGFβ) were measured on wound fluid. Gene expression of matrix extracellular phosphoglycoprotien (MEPE), transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α) were also evaluated on skin biopsies at day 0, 5, 10 and 20. Histopathology, immunohistochemistry and staining of collagen bundles were performed on skin biopsies at 5, 10 and 20 days of wound induction. All data were statistically analyzed. There was a significant interaction between the group and time across all parameters (P < 0.001). The PRP–ZnO NPs group consistently has a great effect on wound size reduction, contraction, healing, epithelialization, and antioxidant activity, along with higher MEPE and PDGFβ expression and arranged parallel collagen bundles, indicating enhanced regeneration. While PRP alone showed the strongest TGF-β increase and anti-inflammatory effect (lowest TNF-α). PRP–ZnO NPs provided the best overall balance between regeneration and inflammation control. All treatments surpassed the control and lanolin groups, which showed minimal improvement. PRP–Lanolin and ZnO NPs offered moderate benefits but were less effective than PRP–ZnO NPs or PRP. ZnO NPs and PRP work together to improve skin wound healing in dogs; PRP promotes regenerative signaling, while ZnO NPs reduce oxidative stress and microbial load.

Cutaneous Radiation Injuries (CRIs) and wounds within an area of radiation exposure (combined injury, CI) are a significant concern for nuclear accidents and radiation combat/terrorist events. CRIs and CI present unique clinical challenges, and effective countermeasures are urgently needed. Here we describe a murine model of CRI and CI in C57BL/6 mice using 16.9 Gy thoracic X-ray irradiation (5.3 Gy/min, 160 kV) ± experimental wound administered immediately. Wound repair and radiation-induced dermatitis were assessed after irradiation. Our previous studies showed that genistein (200 mg/kg, s.c.), administered 24 h prior to irradiation prevented radiation injuries in two murine models. We investigated the effects of genistein in the CI model. Macroscopic and histological analyses showed that radiation significantly delayed wound closure, although wounds did not significantly alter the progression of radiation dermatitis. Genistein improved the early rate of wound closure and significantly reduced dermatitis in mice. Histological analysis showed that genistein improved skin structure and reduced inflammation and fibrosis. Immunohistochemistry showed that genistein attenuated radiation-induced cyclin-dependent kinase inhibitor 1 (p21/waf1) and α-smooth muscle actin and preserved K15 positive skin adult stem cells. These findings suggest that genistein may be an effective prophylactic against CRIs and CI.

The Wound Care Collaborative Community (WCCC) presents this proposed addendum to the 2006 US Food and Drug Administration (FDA) guidance for industry on chronic cutaneous ulcers and burn wounds, with this addendum reflecting nearly 2 decades of scientific and clinical progress. Key gaps in the original guidance have emerged with advances such as the Wound Reporting in Animal and Human Preclinical Studies (WRAHPS) reporting standards and the FDA Biomarker Qualification Program. This proposed addendum updates preclinical recommendations by emphasizing standardized bioassays for biologics, improved animal model selection using WRAHPS criteria, and acknowledgment that animal studies primarily assess safety rather than predict clinical efficacy. Clinical study design recommendations incorporate digital wound assessment technologies; standardized photographic documentation; expanded biomarker use; and innovative umbrella, basket, and platform trial designs to better address biological heterogeneity in chronic wounds. While reaffirming complete wound closure as the most clinically meaningful end point, the addendum also supports the development of validated alternative end points, including patient-reported outcomes. Additional updates include biofilm detection strategies, point of care diagnostic tools, and recognition of differences between clinical trial populations and real world patients. These evidence based recommendations aim to accelerate development of safe and effective wound care products while ensuring alignment with modern regulatory standards.

MMP-9-responsive bFGF/FGF21 patch synergistically piloting the immune remodeling and regeneration of diabetic wounds.