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The present study aimed to investigate the efficacy of different doses of Eucerin-based ointment containing opium compared to routine treatment on experimentally induced burn injury. Male Wistar rats were divided into five experimental groups for topical application: silver sulfadiazine 1% (SSD), Eucerin-based ointment containing opium at concentrations of 0.05%, 0.5%, and 5%, and a Eucerin-based ointment containing 0.05% opium plus SSD (mixed group), following burn wound induction using the comb burn model. An equal volume of different ointments was administered topically. The wound appearances of different groups were photographed at different time points for 21 days. In addition, blood and skin samples were taken 2 and 10 days after thermal injury to assess inflammatory parameters and oxidative stress markers. Also, the liver enzyme activity and kidney function tests were assessed on day 10. The body weight in Opium 5% significantly decreased compared to all other groups after ten days. The wound area was significantly reduced (P<0.05) in three groups: Opium 0.05%, Opium 0.5%, and mixed, compared to the SSD group on days 14 and 21. On day 21, the wound size in the Opium 5% group was significantly larger than that in the SSD group. Significantly lower serum levels of MDA were observed in all groups compared to the SSD group on days 2 and 10. There were no significant differences between treatment groups for concentrations of TNF-α in serum and burned skin samples (p>0.05). The serum concentrations of interleukin-10 in the mixed group were significantly higher compared to the SSD group on day 10. After ten days, groups were not different regarding AST, ALT, and creatinine concentrations (p>0.05). Histopathological analysis revealed that the wound healing efficacy of opium at its lowest concentration (0.05%) surpassed that of silver sulfadiazine (SSD). Furthermore, the combination of 0.05% opium with SSD enhanced the wound repair potential of SSD in burn injuries. This study showed that opium ointment delayed wound closure dose-dependently. Low doses of topical opium ointment and its mixed application with silver sulfadiazine had a protective role in thermal-induced injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mehrpour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Oxidative stress is a major pathological factor that impedes the diabetic wound healing process. Procyanidins (PC) form nanoparticle-vesicles (PPNs) through hydrogen bonding and exhibit good drug delivery capability; however, their application in diabetic wounds is unsatisfactory. To meet the antioxidant needs for treating, high-throughput screening in the natural product library (NPL) under in vitro oxidative stress conditions was conducted to enhance the antioxidant activity of PPNs. HUVECs treated with tert-Butyl Hydroperoxide (TBHP) were established as screening model in vitro. Baicalein (BAI) was identified from over 600  products in the library as the most effective one to combat oxidative stress. Further study showed that PC and BAI may react in equal proportions to synthesize new vesicles, named BAI-PC Polyphenolic nanovesicles (BPPNs), which possess reactive oxygen species (ROS) responsive and antioxidant effects. Network pharmacology indicated that in diabetic wounds, the target genes of PC are mainly enriched in the vascular endothelial growth factor (VEGF)-related pathways, while BAI primarily regulates tyrosine phosphorylation. The complementarity between the two has been validated in both in vitro and in vivo experiments. In summary, the antioxidant drug BAI, identified through high-throughput screening of NPL, could optimize the biological function of PPNs; the newly-synthesized BPPNs may accelerate diabetic wound healing through dual mechanisms of promoting angiogenesis and combating oxidative stress., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Institutional Ethical Committee of Wenzhou Medical University (wydw2023-0243). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Recurrent aphthous stomatitis leads to ulcers that cause severe pain, which is a substantial burden on patients. Equisetum arvense extract (EA) is a crude drug that promotes wound healing of mucous membranes caused by perineal incision during childbirth and alleviates pain. Here, we elucidated the effects of EA on wound healing and pain in a stomatitis hamster model. After stomatitis induction, two different EA doses were continuously applied to the wound area through the intramucosal injection of acetic acid into the cheek pouch (stomatitis/100*EA group and stomatitis/EA group). The body weight and wound area were measured over time, and histological evaluation was performed after stomatitis induction. The wound area was harvested 10 h after stomatitis induction, and gene expression associated with pain and inflammation was analyzed using qPCR. The dorsal root ganglia of the rat spinal cord were isolated, dispersed, and cultured to examine the inhibitory effect of EA on the K+-evoked release of neurotransmitter substance P. In the stomatitis/100*EA group, a significant reduction in wound size was observed compared with the stomatitis/physiological saline (PS) group, and the weight gain rate was considerably higher. The stomatitis/EA group revealed similar histological changes in the wound and wound size as the stomatitis/PS group; however, the weight gain rate was considerably higher on day 7. The stomatitis/EA group suppressed the expression of inflammatory cytokine mRNA, such as Tnf-α and Il-6, and Cox-2 mRNA in the wound area compared with the stomatitis/PS group. EA treatment reduced the upregulated substance P release from the dorsal root ganglia following high-concentration K+ stimulation. EA alleviates pain in a stomatitis model by suppressing inflammatory cytokine expression in the wound area and substance P release from primary sensory neurons. Therefore, using oral care products containing EA is expected to suppress stomatitis pain., Competing Interests: F.S. and M.M. belonged to a collaborative research laboratory of Earth Corporation (https://corp.earth.jp/en/index.html) and Hiroshima University, which used joint research funds to conduct this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Shiba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Increased incidences of antibiotic resistance have necessitated the development of novel wound disinfection strategies with minimal risk of resistance development. This study aimed at developing a biocompatible wound dressing biomaterial with the potential to treat acute and chronic wounds infected with multidrug-resistant Pseudomonas aeruginosa . A multifunctional antibacterial nanoconjugate was synthesized by covalently coupling a synthetically designed peptide (DP1, i.e. , RFGRFLRKILRFLKK) with reduced graphene oxide (rGO). The conjugate displayed antibacterial and antibiofilm activities against multidrug-resistant Pseudomonas aeruginosa . In vitro studies demonstrated 94% hemocompatibility of the nanoconjugate even at concentrations as high as 512 μg mL -1 . Cytotoxicity studies on 3T3-L1 cells showed 95% cell viability, signifying biocompatibility. Owing to these properties, the biomedical applicability of the nanoconjugate was assessed as an antibacterial wound dressing agent. rGO-DP1-loaded wound dressing exhibited enhanced reduction in bacterial bioburden (6 log 10 CFU) with potential for wound re-epithelization (77.3%) compared to the uncoated bandage. Moreover, an improvement in the material properties of the bandage was observed in terms of enhanced tensile strength and decreased elongation at break (%). Collectively, these findings suggest that rGO-DP1 is an effective biomaterial that, when loaded on wound dressings, has the potential to be used as a facile, sustainable and progressive agent for bacterial wound disinfection as well as healing.

Microfluidic-engineered hydrogel microspheres have emerged as a promising avenue for advancements in tissue engineering and regenerative medicine, particularly through the precise manipulation of fluids to achieve personalized composite biomaterials. In this study, we employed microfluidic technology to fabricate hydrogel microspheres (HMs) using Chinese herbal Bletilla striata polysaccharide (BSP) as the primary material. Concurrently, the natural active ingredient 20(S)-protopanaxadiol (PPD) was encapsulated within the HMs in the form of liposomes (PPD-Lipo), resulting in the formation of nanocomposite hydrogel microspheres (PPD-Lipo@HMs) intended for diabetic wound tissue repair. PPD-Lipo@HMs are characterized by the expansive specific surface area, adjustable mechanical properties, and exceptional biocompatibility. PPD-Lipo@HMs can stimulate the production of vascular endothelial factors, which in turn enhances the migration of endothelial cells, the creation of tubes, angiogenesis, and tissue repair. Moreover, the PPD-Lipo@HMs accumulation produces a microsphere scaffold that effectively covers damaged tissues, promoting the attachment, spread, and multiplication of fibroblast and endothelial cells. The polysaccharide material BSP within PPD-Lipo@HMs can modulate the immune microenvironment of the damaged tissue, reducing inflammation, encouraging re-epithelialization and granulation tissue formation, accelerating angiogenesis and collagen deposition, ultimately leading to tissue repair. The findings highlight the superior therapeutic efficacy of the microfluidic-engineered PPD-Lipo@HMs in addressing the complex challenges of diabetic wound tissue repair, thereby affirming the significant potential of microfluidic engineering technology in tissue repair applications., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (SYXK2024-092). Consent for publication: All authors read and agreed to submit the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The treatment of complex or chronic skin wounds caused by burns, trauma, surgery, and genetic disorders has been a worldwide challenge. Small intestinal submucosa (SIS) is a biological material that is widely used in wound healing. How to further expand the wound healing application of SIS, especially in repairing infected wounds, remains a hot research topic for many tissue engineering and biomaterial scholars focusing on skin regeneration. This study uses nanometal-organic frameworks (nano-MOFs), which have not been applied to modify the SIS membrane before, to construct multifunctional dual nano-MOFs @ SIS membrane (dnMOF@SISm). Nano-MOFs are functionalized onto the nanofiber of SIS via in situ self-assembly under mild reaction conditions without any toxic reagent or complex instruments. The dnMOF@SISm can release Co 2+ , Zn 2+ , and bioactive factors, participating in the whole stage of the repair of infected wounds. In vitro , it can regulate the biological activities of various functional cells such as fibroblasts, endothelial cells, and macrophages and shows good antibacterial ability. In the infected full-thickness skin defect rat model, dnMOF@SISm can release metal ions and ligands, killing pathogenic bacteria colonized on the wound surface at the first stage, and then trigger and accelerate the skin repair process via angiogenesis, immune regulation, and collagen deposition. Above all, an efficient, nontoxic, mild self-assembly strategy realizes the functionalization of dual nano-MOFs on the nanofiber of SIS to expand its clinical application scenarios, especially in infected wounds.

Infected chronic wounds, in particular, diabetic wounds, are hard to heal, posing a global health concern with high morbidity and mortality rates. Diabetic full-thickness wounds infected with E. coli belong to the most difficult to heal chronic infected wounds. Here, we introduced tannic acid-modified silicon-based nanoparticles (TA-SiNPs) with broad-spectrum bactericidal activity that bacteria develop minimal resistance to, and they can effectively treat full-thickness wounds in diabetic mice infected with E. coli . Our findings indicate that these TA-SiNPs could achieve 100% antibacterial efficiency against S. aureus and 99.83% against E. coli , underlied by a positive surface charge and tannic acid groups facilitating bacterial membrane chemical composition depletion and depolarization of the membrane. In addition, we showed that spraying TA-SiNPs onto the skin wound of diabetic mice infected with E. coli resulted in wound healing with 98% closure after 12 days, in stark contrast to 49% of the control (PBS) and 68% of the one treated with Ofloxacin. Along with infection inhibition and ROS scavenging, we identified cell proliferation stimulation, inflammatory cytokine downregulation, and healing cytokine upregulation in the lesion, favoring the healing process. This study not only demonstrates the feasibility of employing silicon-based nanoparticles in diabetic wound healing for the first time, but also reports the first broad-spectrum bactericidal silicon nanodots. Furthermore, this provides novel insights into the mechanism of tannin-based nanoparticles disrupting bacterial membranes by depleting their chemical constituents. Our results highlighted that the developed TA-SiNPs are an effective nanomaterial for treating the infected chronic wounds.

The electrospun nanofiber membrane has demonstrated great potential for wound management due to its porous structure, large surface area, mechanical strength, and barrier properties. However, there is a need to develop transparent bioactive nanofibers with strong mechanical properties to facilitate the monitoring of the healing process. In this study, we present an electrospinning-based method for creating transparent (∼80-90%), strong (∼11-13 MPa), and Janus nanofiber membranes. The innovative square pattern architecture of the membrane includes a thin hydrophobic polycaprolactone layer on top of a layer of hydrophilic ethylene-vinyl alcohol nanofiber, which enables the absorption of excess biofluid from the wound and exhibits Janus wettability for water. Furthermore, incorporating 5% chitosan into the composition of the nanofibers accelerates the healing process through its antioxidant properties and antimicrobial activity against various bacteria, including drug-resistant strains. The developed membrane also demonstrates skin-repairing function, quick blood clotting (around 145 ± 12 s), and biocompatibility with keratinocyte (≥90%), as well as in vitro quick cell migration (∼24 h). With a tensile strength of 11-13 MPa, the membrane effectively adheres to the knee joint even after running 4 km. These optimal properties of the electrospun nanofiber membrane make it suitable for effective wound management and inspection of the healing process, without the need for frequent dressing changes.

Hydrogel-based dressing materials offer significant potential in expediting skin wound healing. Nevertheless, they face several challenges: poor adhesion to wound tissues, difficulties in preservation under ambient conditions, and limited multifunctionality to support all wound healing stages. In this work, a dry patch is designed to address these persistent issues by featuring an in situ solid-to-gel transformation and Janus wet tissue adhesiveness. The HGP patch integrates a wet adhesive layer combining dopamine-conjugated hyaluronic acid (HD) and poly(acrylic acid) (PAA), a drug-loading layer comprising gelatin (Gel), and a nonadhesive gelation layer of poly(vinyl alcohol) (PVA) and sodium alginate (SA). This hierarchical structural design confers exceptional wound adhesion, hemostatic capabilities, and antibacterial and antioxidant activities, as well as immune regulatory properties. These attributes collectively support accelerated skin wound healing, particularly in cases complicated by bacterial infections. This research charts an approach to engineer hydrogel-based wound dressings through on-site hydrogel formation, thus advancing the treatment of wounds afflicted with complex infections.

Photothermal therapy (PTT) is an efficient way to combat bacterial infections and circumvent multidrug resistance. However, balancing efficacious bacterial killing and minimizing damage to the surrounding normal tissues remain a great challenge. Herein, a highly cooperative Prussian blue/kaolinite (PB/Kaol) hybrid nanosystem is constructed for antibacterial therapy to accelerate the healing of infected wounds. After hybridization with Kaol, the prepared PB/Kaol forms interfacial Al-O-Fe bonds, a fast charge transfer channel from Kaol to PB, which contributes to the enhanced photothermal effect of PB/Kaol. Additionally, the hydroxyl and Lewis acid-base sites of the Kaol surface could promote the adhesion of PB/Kaol to bacteria, thereby ensuring that as much hyperthermia as possible is focused on the bacteria and minimizing damage to the surrounding healthy tissues. Furthermore, PB/Kaol inherits the anti-inflammatory and hemostasis functions of PB and Kaol, resulting in the rapid healing of infected wounds.

It remains a challenge to effectively regulate the complicated microenvironment during the wound healing process. The optimization of synergistic action of angiogenesis and inflammation is considered critical for quicker scarless wound regeneration. Here, the silk nanofiber (SNF) acts as a multifunctional carrier to load hydrophobic asiaticoside (AC) and hydrophilic Mg 2+ , and also serves as an element to assemble injectable hydrogels, forming a bioactive matrix with improved angiogenic and anti-inflammatory capacities (SNF-AC-Mg). Mg 2+ and AC distributed homogeneously inside the silk nanofiber hydrogels without compromising the mechanical performance. Both Mg 2+ and AC released slowly to continuously tune both angiogenic and inflammatory behaviors. The hydrogels exhibited good biocompatibility, inflammation inhibition, and pro-angiogenic properties in vitro , suggesting the synergistic bioactivity of AC and Mg 2+ . In vivo analysis revealed that the synergistic action of AC and Mg 2+ resulted in better M2-type polarization of macrophages and angiogenesis during the inflammatory phase, while effectively achieving the inhibition of excessive accumulation of collagen and scar formation during the remodeling phases. The quicker scarless regeneration of the defects treated with SNF-AC-Mg implies the priority of SNFs in designing bioactive niches with complicated cues, which will favor the functional recovery of different tissues in the future.

Wound healing is a complex and dynamic process supported by several cellular events. Around 13 million individuals globally suffer from chronic wounds yearly, for which dressings with excellent antimicrobial activity and cell viability (>70%, as per ISO 10993) are needed. Excessive use of silver can cause cytotoxicity and has been linked to increasing antimicrobial resistance. In this study, HDI Ag foam was synthesized using a safer hexamethylene diisocyanate-based prepolymer (HDI prepolymer) instead of commonly used diisocyanates like TDI and MDI and substantially lower Ag content than that incorporated in other Ag foams. In vitro characteristics of the HDI Ag foam were evaluated in comparison with leading clinically used foam-based dressings. All dressings underwent a detailed characterization in accordance with industrially accepted BS EN 13726 standards. The HDI Ag foam exhibited highest antimicrobial efficiency against S. aureus and P. aeruginosa (static condition), with the lowest amount of Ag (0.2 wt%) on the wound contact surface. The extracts from HDI Ag foam showed superior cell viability (>70%), when tested on the L929 mouse fibroblast cell line. Measurements of moisture vapor transmission, fluid handling, physico-chemical and mechanical properties ensured that the HDI foam was clinically acceptable for chronic wound patients., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Treating sunburn and other UV-induced skin damage issues remains a significant challenge in the field of dermatology. In this study, we synthesized a highly bioactive recombinant type III collagen (rCol III) to accelerate the healing of UV-damaged skin. The high-purity rCol III demonstrated excellent biocompatibility and bioactivity, significantly promoting the adhesion, proliferation, and migration of HFF-1 cells. In a mouse UV-damage model, Combo evaluations demonstrated that rCol III contributed to restore transepidermal water loss (TEWL) values of UV-damaged skin to normal levels. Histological analysis further confirmed that rCol III substantially accelerated skin repair by enhancing collagen regeneration. Additionally, rCol III facilitated the regeneration of zebrafish tail fin tissue and alleviated shrinkage caused by excessive UV exposure. The biocompatible and bioactive rCol III offers a novel strategy for treating UV-induced skin damage, holding immense potential for applications in skin tissue engineering.

Nanotechnology enables the manipulation of materials at the nanoscale, offering innovative solutions in various fields. Nanoparticles, with their small size and unique properties, have significant applications in the biomedical filed. The current study was designed to assess the biological applications of self-synthesized cobalt carbonate (CoCO 3 ) nanoparticles. The crystalline structure and chemical composition of the CoCO 3 -NPs were confirmed by SEM, XRD, and FTIR techniques. We observed the 16.58 nm size of novelly synthesized CoCO 3 NPS. The scanning electron microscope study confirmed a uniform cubic spinel structure. The biocompatibility and antimicrobial activity were checked in an invitro setup. We exposed albino mice to these synthesized NPs to study wound healing and metabolic effects. The results of biocompatibility analysis indicated hemolytic activity in a dose-dependent way, which showed no cytotoxic effect except at a higher concentration. Furthermore, the results showed enhanced wound healing processes in CoCO 3 -NP-treated albino mice as compared to the control group. CoCO 3 -NPs have considerable effect on the thyroid hormone and insulin levels in albino mice. The levels of T3, T4, and insulin were increased in a dose-dependent manner. Interactions between CoCO 3 -NPs and thyroxine and insulin were confirmed through molecular docking. We confirmed the antimicrobial efficiency of the nanoparticles using MIC values and zones of inhibition against Staphylococcus haemolyticus and Staphylococcus aureus. Despite their concentration-dependent biocompatibility concerns, the results are promising, as CoCO 3 -NPs hold potential for use in medical practice, particularly in advanced wound management and microbe inhibition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The first barrier of the human body is the skin, and more serious harm may occur when skin wound healing is delayed. One of the components of enamel matrix proteins is amelogenin, which inhibits inflammation and promotes periodontal tissue regeneration. However, its role in skin wound healing and angiogenesis is inconclusive. Thus, this study aimed to assess the therapeutic effect of recombinant human amelogenin (rhAM) on mouse skin wounds and to determine its effect on angiogenesis and its underlying mechanism. rhAM was expressed in Escherichia coli and purified using the optimized acetic acid method. A skin injury mouse model was established to explore the effects of rhAM on skin wound healing. After treatment with rhAM for 7 days, the wound healing rate was calculated, and the therapeutic effect of rhAM on skin wounds was assessed using hematoxylin & eosin (HE), Masson, and CD31 immunofluorescence staining. The expression of growth and inflammatory factors in wound tissues were detected using Western Blot. In addition, the rhAM effects on the proliferation and migration of human umbilical vein endothelial cells (HUVEC) and mouse fibroblasts (NIH 3T3) were studied in vitro using the Cell Counting Kit-8, cell scratch, cytoskeleton staining, and qPCR. The rhAM effect on HUVEC angiogenesis and its potential mechanism was studied using tube formation and Western Blot. The results showed that the purity of the obtained rhAM was more than 90 % using the optimized acetic acid method, and high-dose rhAM treatment could improve wound healing rate in mice. Additionally, more blood vessels and collagen were produced in the skin wound, and the expression of angiopoietin-related protein 2 (ANGPTL2) and transforming growth factor (TGF)-β1 was upregulated; however, that of interleukin-6 was down-regulated. We also found that rhAM promoted the proliferation and migration of HUVEC and NIH 3T3, the mRNA levels of vascular endothelial growth factor (VEGF), fibroblast growth factor, TGF-β1 and ANGPTL2 in HUVEC cells were upregulated, and expression of VEGF and phosphorylation of the p38 mitogen-activated protein kinase were activated. Therefore, rhAM could promote skin wound healing by upregulating angiogenesis and inhibiting inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The prolonged existence of chronic wounds heightens the risk of patients experiencing chronic pain, necrosis, and amputation. Dental pulp stem cells (DPSCs) have garnered attention due to their potential immunomodulatory and tissue repair regenerative effects in the management of chronic wounds. However, stem-cell-based therapy faces challenges such as malignant differentiation, immune rejection, and long-term effectiveness. To overcome these challenges, we proposed a chronic wound therapy using a hydrogel derived from human-originated dental pulp stem cell lysate (DPSCL). Our data indicate that, with the degradation of the dental pulp stem cell lysate-based hydrogel (DPSCLH), the slowly released cell lysates recruit anti-inflammatory M2 macrophages and promote the proliferation, migration, and keratinization of HacaT cells. In addition, in vivo studies revealed that DPSCLH avoids immune rejection reactions and induces a long-term accumulation of endogenous M2 macrophages. In a mouse model of diabetic wounds, DPSCLH effectively modulates the inflammatory microenvironment around diabetic wounds, promotes the formation of the stratum corneum, and facilitates the healing of wounds, thus holding tremendous potential for the treatment of diabetic wounds.

In the present study, we have developed an agar-based asymmetric Janus nanofibrous wound dressing comprising a support and an electrospun layer with antibacterial and antioxidant properties, respectively, to facilitate healing effectively. The support layer containing agar and silver nitrate was fabricated by using solvent casting for sustained release, combating the dose-dependent cytotoxicity of silver nanoparticles, where nanoparticles were synthesized using a one-pot reduction method. The electrospun layer, fabricated with a mixture of agar and polycaprolactone infused with gallic acid, was electrospun over the support layer to impart antioxidant properties. Characterizations using UV-vis spectroscopy, transmission electron microscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy validated the synthesis of nanoparticles in 10-20 nm diameter and the asymmetric Janus dressing. The developed Janus nanofibrous structure exhibited 98% porosity, excellent fluid-handling properties, a moisture permeability of 1200 g/m 2 /day, and a water absorption of ∼250%. Moreover, the time-kill assay confirmed potent bacteriostatic effect against Gram-positive and Gram-negative bacteria, and sustained release of silver nanoparticles followed the Korsmeyer-Peppas model. With over 90% free radical scavenging efficacy, 37% degradation in 7 days, and less than 2% hemolysis, the dressings demonstrated exceptional antioxidant, biodegradable, and hemocompatible properties. The biocompatibility assessment further confirmed its cytocompatible efficacy, with more than 79% wound closure in the wound scratch assay. Most importantly, in vivo studies demonstrated the efficacy of the developed Janus dressing, promoting over 97% healing within 12 days of injury with higher epithelial formation. Overall, the in vitro and in vivo assessment of the developed Janus dressing confirmed its potential to function as a versatile and effective material for wound care applications.

Individuals with diabetes frequently face serious challenges, including delayed wound healing and increased risk of infection. Notably, the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair, reducing the risk of infection, and enhancing overall skin health. Research has predominantly emphasized the re-epithelialization of diabetic wounds, with a paucity of in-depth studies on hair follicle regeneration. In the current study, we explored the effects of a bioactive amphibian-derived peptide, Cy RL-QN15 , on promoting hair regeneration in a diabetic skin model. In vivo experiments demonstrated that local treatment with Cy RL-QN15 not only accelerated wound healing of scalded skin on the backs of diabetic Kunming (KM) mice but also improved growth of damaged hair follicles. Additionally, back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy RL-QN15 treatment. Further analysis indicated that the hair-regenerating effects of Cy RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as c-MYC, Cyclin D1, and Lef1, ultimately inducing hair regeneration. This study not only reveals the robust effects of the bioactive peptide Cy RL-QN15 in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.

Deep skin wounds require grafting with a skin substitute for treatment. Despite many attempts in the development of an affordable and efficient skin substitute, the repair of deep skin wounds still remains challenging. In the current study, we present a 3D sponge composite made from human placenta (a disposable organ) and sodium alginate with exceptional properties for skin tissue engineering applications. Toward this goal, different proportions of alginate (Alg) and decellularized placenta scaffold (DPS) were composited and freeze-dried to generate a 3D sponge with the desired biomechanical and biological features. Comprehensive in vitro, in ovo, and in vivo characterizations were performed to assess the morphology, physical structure, mechanical behaviors, angiogenic potential, and wound healing properties of the composites. Through these analyses, the scaffold with optimal proportions of Alg (50%) and DPS (50%) was found to have superior properties. The optimized scaffold (Alg50/DPS50) was applied to the full-thickness wounds created in rats. Our data revealed that the addition of DPS to the Alg solution caused a significant improvement in the mechanical characteristics of the scaffold. Remarkably, the fabricated composite scaffold exhibited mechanical properties similar to those of native skin tissue. When implanted into the full-thickness wounds, the Alg50/DPS50 composite scaffold promoted angiogenesis, re-epithelialization, and granulation tissue formation, as compared to the group without a scaffold. Overall, our findings underscore the potential value of this hybrid scaffold for enhancing skin wound healing and suggest an Alg50/DPS50 composite for clinical investigations.

Objective: Diabetes mellitus (DM) delays wound healing, including those following tooth extractions. Curcumin (CCM) can promote soft tissue and bone healing. The present study investigates the healing effects of CCM on tooth extraction sockets in diabetic rats., Methodology: Ninety-six male Wistar rats were divided into the following four groups: Control+Corn Oil (CO), Control+CCM, DM+CO, and DM+CCM. Each group was subdivided into 7-, 14-, and 28-day time point subgroups comprising eight rats. All animals had their maxillary first molars extracted. CCM-treated rats received 100 mg/kg of CCM orally for 7, 14, and 28 days. The lesion area was evaluated using macroscopic analyses, whereas socket healing was assessed by hematoxylin and eosin staining. Keratinocyte growth factor (KGF), Runt-related transcription factor 2 (Runx2), and collagen type I (COL1) expression levels were obtained using quantitative polymerase chain reaction (qPCR). Bone healing was analyzed by means of microcomputed tomography (μCT)., Results: After 7 days, the groups showed no significant differences in lesion area and by day 14, no lesions were present. CCM treatment increased KGF mRNA expression in diabetic rats; however, diabetic rats showed delayed bone healing unrelated to CCM. CCM treatment resulted in increased Runx2 mRNA expression only in control rats, whereas COL1 mRNA expression remained unaffected by CCM., Conclusion: CCM shows potential as a soft tissue healing enhancer in diabetic rats and could serve as an additional treatment to promote soft tissue repair in diabetic individuals. Although CCM did not impact alveolar bone healing, it may enhance bone healing in other skeleton regions.

Chronic wound infection has become a global health problem, with bacterial biofilms, which are difficult to penetrate using traditional antibiotics, considered the primary cause of recurrent infection and delayed healing in chronic wounds. In recent years, the outstanding performance of nanomaterials in controlling biofilm infections has been widely acknowledged, and these materials are regarded as highly promising for chronic wound infection management. The formation and structure of chronic wound biofilms undergo complex dynamic changes. Therefore, a deep understanding of the underlying causes of repeated wound infections and the specific antibacterial mechanisms of nanomaterials at different stages of biofilm formation is crucial for effective "chronic wound infection management". This review first reveals the relationship between biofilms, wound chronicity, and recurrent infections. Secondly, it focuses on the four stages of chronic wound biofilm formation: (1) adhesion stage, (2) aggregation and promotion stage, (3) maturation stage, and (4) regeneration and dissemination stage. It also comprehensively summarizes the specific antibacterial mechanisms of nanomaterials. This study analyzes essential factors affecting the control of chronic wound biofilms by nanoparticles from various perspectives, such as the material itself, the local wound environment, and the systemic host response. Finally, the limitations and potential future trends in current research are discussed. In summary, nanoparticles represent a promising strategy for combating chronic wound biofilm infections, and this review provides new insights for alternative adjuvant therapies in managing bacterial biofilm infections in chronic wounds., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Jing et al.)

Bacterial infections, especially induced by multidrug-resistant pathogens, have become a significant global health concern. In the infected tissues, biofilms not only serve as a source of nutrients but also act as protective barriers that impede antibiotic penetration. Herein, we developed tea polyphenols epigallocatechin gallate (EGCG) Au nanoparticles (E-Au NPs) through direct one-step self-assembly methods by EGCG chelating with Au ions to eradicate antibiotic-resistant bacteria methicillin-resistant Staphylococcus aureus (MRSA) and prevent the formation of biofilm under near-infrared (NIR) irradiation. The outstanding antibacterial effect involved in mild photothermal therapy, reactive oxygen species production, pathogenicity-related genes regulation, and quinoprotein formation that were specific to the polyphenol-based NPs. The excellent antibacterial and anti-inflammatory therapeutic efficacy of E-Au NPs was validated and topically applied in murine MRSA-infected skin wounds and keratitis model in vivo to kill bacteria, reduce the inflammation response and promote wound healing. Furthermore, the ophthalmic and systemic biosafety profiles were thoroughly evaluated while no significant side effects were revealed achieving a balance between high-efficiency antibacterial properties and biocompatibility. This study provides an effective therapeutic agent of metal-phenolic materials for superficial tissue infection with favorable prognosis and potential in clinical translation., Competing Interests: Declarations Ethics approval and consent to participate The experimental protocol concerning animals used in this work was approved by the Animal Ethics Committee, the Second Affiliated Hospital, School of Medicine, Zhejiang University (Approval No. 2022 − 164). Consent for publication All authors involved in this study have provided their consent for the publication of the research findings. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Natural polysaccharide-based active-ingredient carriers have been a source of great concern for a long time. In order to explore potential antibiotics and probiotics carriers, a novel injectable chondroitin sulfate/salecan (CS) hydrogel was constructed by forming dynamic hydrazone bonds. Scanning electron microscope (SEM), proton nuclear magnetic resonance ( 1 H NMR), Fourier transform infrared spectroscopy (FTIR), bacteriostatic test, and rheological experiments were used to investigate the chemical structure, inherent morphology, and enzymatic corruption of the hydrogel in vitro. The resulting hydrogels exhibited ideal probiotics loading capacity, drug release behavior, excellent antimicrobial activity and variable properties. Crucially, owing to its exceptional biocompatibility and reversible crosslinking network, this hydrogel can function as a three-dimensional extracellular matrix for cells, enabling cells to maintain high vitality and proliferation, and promote wound healing. The aforementioned findings indicated that this novel hydrogel can be a promising candidate as an active-ingredient carrier and scaffold material for tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Wound healing is a natural process that can be disrupted by disease. Nanotechnology is a promising platform for the development of new therapeutic agents to accelerate acute and chronic wound healing. Drug delivery by means of nanoparticles as well as wound dressings have emerged as suitable options to improving the healing process. The characteristics of mesoporous silica nanoparticles (MSNs) make them efficient carriers of pharmaceutical agents alone or in combination with dressings. In order to maximize the effect of a drug and minimize its adverse consequences, it may be possible to include targeted and intelligent release of the drug into the design of MSNs. Its use to facilitate closure of adjacent sides of a cut as a tissue adhesive, local wound healing, controlled drug release and induction of blood coagulation are possible applications of MSNs. This review summarizes research on MSN applications for wound healing. It includes a general overview, wound healing phases, MSN formulation, therapeutic possibilities of MSNs and MSN-based drug delivery systems for wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dressings should protect wounds, promote healing, absorb fluids, and maintain moisture. Bacterial cellulose is a biopolymer that stands out in biomaterials due to its high biocompatibility in several applications. In the area of dressings, it is already marketed as an alternative to traditional dressings. However, it lacks any intrinsic activity; among these, the need for antimicrobial activity in infected wounds stands out. We developed a cationic cellulose film by modifying cellulose with 1-(5-carboxypentyl)pyridin-1-ium bromide, enhancing its wettability (contact angle: 26.6°) and water retention capacity (2714.37 %). This modified film effectively retained oxacillin compared to the unmodified control. Liposomal encapsulation further prolonged oxacillin release up to 11 days. Both oxacillin-loaded films and liposomal formulations demonstrated antimicrobial activity against Staphylococcus aureus. Our findings demonstrate the potential of chemically modified cellulose as a platform for controlled anionic antibiotics and/or their formulations delivery in wound care., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Renato Ribeiro Viana, Karina Andressa Sedans, Bruna Conceição Costa Silva, Cesar Augusto Tischer and Luis Fernando Cabeça have patent pending to BR10202202711. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rapid regeneration of the injured tissue or organs is necessary to achieve the usual functionalities of the damaged parts. However, bacterial infections delay the regeneration process, a severe challenge in the personalized healthcare sector. To overcome these challenges, 3D-printable multifunctional hydrogels of Zn/tannic acid-reinforced glycol functionalized chitosan for rapid wound healing were developed. Polyphenol strengthened intermolecular connections, while glutaraldehyde stabilized 3D-printed structures. The hydrogel exhibited enhanced viscoelasticity (G'; 1.96 × 10 4  Pa) and adhesiveness (210 kPa). The dual-crosslinked scaffolds showed remarkable antibacterial activity against Bacillus subtilis (∼81 %) and Escherichia coli (92.75 %). The hydrogels showed no adverse effects on human dermal fibroblasts (HDFs) and macrophages (RAW 264.7), indicating their superior biocompatibility. The Zn/TA-reinforced hydrogels accelerate M2 polarization of macrophages through the activation of anti-inflammatory transcription factors (Arg-1, VEGF, CD163, and IL-10), suggesting better immunomodulatory effects, which is favorable for rapid wound regeneration. Higher collagen deposition and rapid re-epithelialization occurred in scaffold-treated rat groups vis-à-vis controls, demonstrating superior wound healing. Taken together, the developed multifunctional hydrogels have great potential for rapidly regenerating bacteria-infected wounds in the personalized healthcare sector., Competing Interests: Declaration of competing interest The authors declare that no conflicts of financial interests or personal relationships have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Konjac glucomannan (KGM) as an emerging natural polymer has attracted increasing interests owing to its film-forming properties, excellent gelation, non-toxic characteristics, strong adhesion, good biocompatibility, and easy biodegradability. Benefiting from these superior performances, KGM has been widely applied in the construction of multiple composite materials to further improve their intrinsic performances (e.g., mechanical strength and properties). Up to now, KGM-based composite materials have obtained widespread applications in diverse fields, especially in the field of biomedical. Therefore, a timely review of relevant research progresses is important for promoting the development of KGM-based composite materials. Innovatively, firstly, this review briefly introduced the structure properties and functions of KGMs based on the unique perspective of the biomedical field. Then, the latest advances on the preparation and properties of KGM-based composite materials (i.e., gels, microspheres, films, nanofibers, nanoparticles, etc.) were comprehensively summarized. Finally, the promising applications of KGM-based composite materials in the field of biomedical are comprehensively summarized and discussed, involving drug delivery, wound healing, tissue engineering, antibacterial, tumor treatment, etc. Impressively, the remaining challenges and opportunities in this promising field were put forward. This review can provide a reference for guiding and promoting the design and biomedical applications of KGM-based composites., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Long-term inflammation and impaired angiogenesis are the main reasons for the difficulty of diabetic wound healing. What to do to effectively promote vascular endothelial cell response and immune cell reprogramming is the key to diabetic skin healing. However, contemporary therapies cannot simultaneously coordinate the promotion of vascular endothelial cells and macrophage polarization, which leads to an increased rate of disability in patients with chronic diabetes. Therefore, we developed a method of repair composed of self-assembling Prussian blue nanoenzymes, which achieved synergistic support for the immune microenvironment, and also contributed to macrophage polarization in the tissue regeneration cycle, and enhanced vascular endothelial cell activity. The template hydrothermal synthesis PB-Zr nanoplatform was prepared and locally applied to wounds to accelerate wound healing through the synergistic effect of reactive oxygen species (ROS). PB-Zr significantly normalized the wound microenvironment, thereby inhibiting ROS production and inflammatory response, which may be because it inhibited the M1 polarization of macrophages in a rat model of wound. PB-Zr treatment significantly promoted the activity of vascular endothelial cells, which better promoted the growth and regeneration of other tissues in the body. The results confirmed the disease microenvironment of PB-Zr-mediated wound therapy and indicated its application in other inflammation-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Persistent inflammation and bacterial infection commonly occur during the wound healing process, necessitating urgent development of effective strategies for treating drug-resistant bacterial infections. In this study, bismuth vanadate (BiVO 4 ) was successfully synthesized as an antibacterial agent that promotes wound healing. Through In vitro antibacterial experiments, it was observed that the prepared BiVO 4 exhibited excellent performance in catalyzing H 2 O 2 to produce hydroxyl radicals (OH) at a lower concentration (0.2 mg mL -1 ), resulting in significant antibacterial effects against Gram-negative Extended-Spectrum β-Lactamases-Producing Escherichia coli (ESBL-E. coli) strains. Furthermore, biosafety tests, cell scratch experiments, and ESBL-E. coli infected wound rat model experiments demonstrated high biocompatibility of BiVO 4 with a cell survival rate exceeding 85 %. Additionally, BiVO 4 promoted the production of vascular endothelial growth factors and fibroblasts migration while contributing to collagen production, effectively facilitating immune reconstruction at the wound site. By integrating peroxidase (POD)-like under acidic conditions (pH 4) and catalase (CAT)-like catalytic activities at under neutral conditions (pH 7), BiVO 4 exhibited the ability to activate free radical sterilization and accelerate wound healing by activating O 2 . Therefore, our findings provide evidence for a dual enzyme regulatory mechanism involving antibacterial properties and promotion of wound tissue reconstruction for potential application in both antibacterial treatment and wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hyaluronic acid (HA), as an extracellular matrix, is known to promote wound healing, and its bioactivity is affected by molecular weight. However, the mechanism of LMW-HA on cells migration remains unclear. In this study, we investigated the effect of LMW-HA on cells migration and the underlying mechanism by employing proteomics. The scratch assay showed that LMW-HA can significantly enhance the migration of keratinocytes in vitro, and ten differentially expressed proteins (DEPs) were found to be associated with wound healing through proteomics and network pharmacology. The result of bioinformatic analysis indicated that these DEPs are involved in positive regulation of cell motility and cellular component movement. Moreover, protein targets of key pathways were further validated. The findings suggest that LMW-HA can promote wound healing by accelerating epithelization via the HIF-1α/VEGF pathway, which provides new insight and reference for HA to enhance cells migration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mesenchymal stem cell (MSC)-derived exosomes (EXs) have emerged as promising therapeutic agents for wound healing. However, the optimal conditions for manufacturing MSC-derived EXs that maximize their wound-healing potential have yet to be established. Hence, we compared the efficacy of five different MSC culture media, including three different serum-free, a platelet-supplemented, and a fetal bovine serum-supplemented media, in exosome manufacturing for wound healing applications. Although umbilical cord-derived MSCs (UCMSCs) cultured in these media exhibited similar proliferation, morphology, MSC surface marker expression, and stemness, EXs derived from UCMSCs cultured in different culture media displayed varying levels of growth factors and cytokines. Notably, EXs derived from platelet-supplemented media (DM-PLT&#95;EXs) exhibited significantly higher concentrations of keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF-A), platelet-derived growth factor (PDGF-BB), interleukin 6 (IL-6), interleukin 7 (IL-7), and interleukin 8 (IL-8) than EXs from other media. These differences correlated with the superior capability of DM-PLT&#95;EXs to promote human skin fibroblast proliferation and stimulate angiogenesis of human umbilical vein endothelial cells, making them a more suitable choice for wound healing applications. Our findings emphasize the significance of the culture medium selection in tailoring the therapeutic potential of UCMSC-derived EXs for wound healing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The ability to heal from wounds is perhaps the most important biological function that ensures our survival and perpetuation. Cutaneous wound healing typically consists of four characteristic stages, namely hemostasis, inflammation, proliferation, and remodeling, which are carefully carried out by coordinated actions of various cells, cytokines, and hormones. Incoordination of these steps may impede complete and efficient reconstruction and functional recovery of wounds or even lead to worsened outcomes. Hormones, as powerful modulators of organ functions, participate in multiple steps of the wound healing process and play a pivotal role by choreographing the complex interplay of cellular and molecular events. Leveraging the regulatory effects of hormones to enhance the healing process, hormonal therapy has emerged as a promising approach in the clinical treatment of wounds. Current research has focused on determination of the optimal dosages, delivery methods, and combinations of hormonal therapies to maximize their therapeutic benefits while minimizing potential side effects. This review highlights the molecular mechanisms, clinical benefits and side effects of the most commonly used hormones in clinical treatment of wounds., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

As the incidence of chronic wounds increases, the requirements for wound dressings are rising. The specific aim of this study is to propose a novel gallic acid (GA) functionalized silk fibroin (SF) and gelatin (Gel) composite wound dressing in which GA is used as an antibacterial and wound healing substance. Via electrospinning, SF, Gel, and GA mixed solutions could be conveniently fabricated into a composite nanofiber mat (SF-Gel-GA), consisting of uniform fibers with an average diameter around 134.57 ± 84 nm. The internal mesh structure of SF-Gel-GA provides sufficient drug loading capacity, proper moisture permeability, and proper degradation rate. SF-Gel-GA presents excellent biocompatibility. NIH-3T3 fibroblast cells could adhere and spread stably on the SF-Gel-GA surface with slightly promoted proliferation. In the presence of SF-Gel-GA, the growth of both Gram-positive and Gram-negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa , is significantly inhibited in both plate and suspension cultures. A cutaneous excisional mouse wound model proves the efficient ability of SF-Gel-GA to promote wound healing. Compared with pure SF dressing and commercial Tegaderm Hydrocolloid 3M dressing, the wound closure rate with SF-Gel-GA treatment is significantly improved. The histological assessments further demonstrate SF-Gel-GA could facilitate collagen deposition, neovascularization, and epithelialization at wound sites to promote wound healing. In conclusion, a novel SF-Gel-GA composite wound dressing with efficient wound healing activities have been developed for chronic wound treatment with broad healing potential., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Zirconia is the most promising implant abutment material due to its excellent aesthetic effect, good biocompatibility and corrosion resistance. To obtain ideal soft tissue sealing, the implant abutment surface should facilitate cell adhesion and inhibit bacterial colonization. In this study, pre-sintered zirconia was placed in a suspension of titania (TiO 2 ) and zirconium oxychloride (ZrOCl 2 ) and heated in a water bath for dense sintering. A titania coating was prepared on the zirconia surface and subjected to UV irradiation. The surface morphology, elemental composition and chemical state of each group of samples were analyzed by scanning electron microscope, x-ray energy spectrometer, x-ray photoelectron spectroscopy and x-ray diffraction. The responses of human gingival fibroblasts (HGFs) and common oral pathogens Streptococcus mutans ( S. mutans ) and Porphyromonas gingivalis ( P. gingivalis ) to modified zirconia were systematically assessed. Our findings demonstrated that the surface of titania-coated zirconia after UV irradiation produced a large number of hydroxyl groups, and its hydrophilicity was significantly improved. Meanwhile, the UV irradiation also greatly removed the hydrocarbon contaminants on the surface of the titania-coated zirconia. The UV-treated titania coating significantly promoted the proliferation, spreading, and up-regulation of adhesion-related genes and proteins of HGFs. Furthermore, the titania coating irradiated with UV could reduce the adhesion, colonization and metabolic activity of S. mutans and P. gingivalis . Therefore, UV irradiation of titania-coated zirconia can promote the biological behavior of HGFs and exert a significant antibacterial effect, which has broad clinical application prospects for improving soft tissue integration around zirconia abutments., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Burn injuries cause severe pain, infection risks, psychological distress, financial burdens, and mortality, necessitating effective care. Aloe vera, a traditional burn remedy, shows wound-healing potential, but its analgesic effects and efficacy with varying burn severity are uncertain. This study aims to investigate A. vera's effect on wound healing, pain management, and infection prevention in patients with burns. A systematic search on PubMed, Embase, and CENTRAL was performed on October 9, 2023, for randomized controlled trials (RCTs). The risk of bias was examined using the Cochrane risk-of-bias tool (version 2), and the meta-analysis was carried out using a random-effects model. The primary outcome was wound-healing time, with secondary outcomes examining pain severity and wound infection. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence for each outcome. Nine RCTs were included in the current study, of which 6 provided data on the primary outcome. Aloe vera significantly reduced mean wound-healing time compared to other topicals (mean difference [MD] -3.76 days; 95% CI, -5.69 to -1.84). Additionally, the meta-analysis of the secondary outcomes found no significant differences in pain reduction (MD -0.76 points; 95% CI, -1.53 to 0.01) and wound infection risk (risk ratio 1.10; 95% CI, 0.34-3.59) between A. vera and control groups. In conclusion, A. vera expedites wound healing in patients with second-degree burns without increased infection risk compared to other antimicrobial agents. The analgesic effects on burn injuries remain uncertain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Etherified Carboxymethylcellulose Matrix (eCMC) is a revolutionary application of carboxymethylcellulose (CMC) in wound care, known for its potential in hemostasis and tissue regeneration. This study aims to investigate the mechanism of eCMC in tissue healing by establishing a rat burn model and administering eCMC as a treatment. The objective is to analyze cytokines and inflammatory mediators using a Cytokine Array and histochemical staining to understand the effects of eCMC on tissue regeneration. A rat burn model was created, and eCMC was applied as a treatment. Tissue samples were collected at multiple time points to assess the expression of cytokines and inflammatory mediators using a Cytokine Array. In addition, histochemical staining was performed to evaluate tissue regeneration factors. eCMC induced the expression of endogenous cytokines, particularly vascular epithelial growth factor and platelet-derived growth factor, while inhibiting inflammatory cytokines such as CINC-1, CINC-2, and MMP-8. This dual action facilitated wound healing and mitigated the risk of infection. eCMC demonstrates promising potential for enhancing skin regeneration. Further research is warranted to delve into the precise mechanism of eCMC's cytokine regulation. In vitro and in vivo studies should be conducted to comprehensively investigate the therapeutic capabilities of eCMC in wound healing., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association.)

Burn wounds are one of the most hazardous issues, globally. Silkworm produces a protein called sericin. Sericin assists in wound healing by facilitating the proliferation of keratinocytes and fibroblasts, while turmeric is potentially helpful in wound healing because of its antioxidant, anti-inflammatory, and anti-infectious activities. The current study aimed to investigate the synergetic and individual effects of turmeric, sericin, and their nanoparticles on burn wounds in mice. The female mice having age of 2 months (each weighing 29-30 g) were arbitrarily distributed in 7 groups. Five mice were added to each group. Burn wounds were induced in mice by using a hot metal rod. Burn wounds were evaluated histologically and morphologically. Turmeric nanoparticles substantially improved the wound contraction area as compared to the negative control group and other treatment groups. The serum level of glutathione (4.9 ± 0.1 µmol/L), catalase (6.0 ± 0.2 mmol/mL), glutathione peroxidase (183.4 ± 5.1 U/L), and superoxide dismutase (194.6 ± 5.1 U/mL) was significantly increased in the turmeric nanoparticles (TNPs) group as compared to the negative control (2.8 ± 0.1 µmol/L, 3.5 ± 0.1 mmol/mL, 87.8 ± 3.0 U/L, and 92.0 ± 4.8 U/mL respectively). The minimum levels of malondialdehyde (3.8 ± 0.2 mmol/L) were noticed in the TNPs group contrary to the negative control (7.4 ± 0.2 mmol/L). The restoration of the epidermis was also observed to be faster in the TNPs group as compared to all other treatment groups. The histopathological analysis also demonstrated the effectiveness of turmeric, sericin, and their nanoparticles. In conclusion, turmeric, sericin, and their nanoparticles are effective in improving the healing process of burn wounds, but TNPs showed the most effective results as compared to all other treatment groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Tendon injuries present a significant challenge for independent repair, and can progress into tendinopathy over time, highlighting the importance of early intervention. Dendritic cell-derived exosomes (DEXs) has been shown to shift the polarization of M1 macrophages, the predominant inflammatory cells in the early stages of tendon injury. This study introduces a therapeutic approach that effectively manages inflammation while promoting regeneration in the treatment of tendinopathy., Methods: The purification and characterization of DEXs were meticulously conducted. Experiments were carried out using an Achilles tendon rupture mouse model, with weekly DEXs treatment starting on postoperative day (POD) 4. In vitro, the function of DEXs was assessed by coculturing them with tendon stem/progenitor cells (TSPCs) in culture medium containing IL-1β. Tendon healing progress was evaluated using Sirius Red staining, Masson's trichrome staining, biomechanical testing, and immunofluorescence microscopy. The inflammatory microenvironment of injured tendons was evaluated using the Luminex procedure and flow cytometry analysis., Results: DEXs treatment significantly enhanced tendon cell differentiation, promoted collagen type I synthesis, and inhibited collagen type III synthesis, thereby expediting tendon healing. Furthermore, DEXs treatment improved the inflammatory microenvironment by reducing multiple cytokines (IL-1β, IL-4, IL-6, TNF-α, and IFN-γ) and induced the conversion of M1 macrophages to M2 macrophages by activating the PI3K/AKT pathway., Conclusion: DEXs demonstrated a potent ability to promote tendon healing while ameliorating the inflammatory microenvironment, suggesting their potential as a therapeutic approach to prevent the development of tendinopathy., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Chen et al.)

Nanocomposite films of (30% PVC/70% PVDF) blend containing silver nanoparticles were synthesized via pulsed laser ablation route (PLA). Changes in physical characterization of PVC/PVDF blend before and after the incorporation of AgNPs have been studied. FTIR results confirms the interaction between AgNPs and PVC/PVDF. XRD results obtain the existence of peak at 38.42̊ in sample PVC/PVDF/Ag4 which confirm the embedded AgNPs in the high concentration. SEM photos confirm the distribution of silver nanoparticles on the surface of the sample in spherical shape which approved the dispersion of silver nanoparticles in PVC/PVDF blend. The inhibitory zone diameters observed for PVC/PVDF/Ag4 against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Bacillus cereus were recorded as 11 ± 1, 10 ± 1, 15.7 ± 0.6, and 17.7 ± 0.6, respectively. PVC/PVDF/AgNPs nanocomposite film could be suggested for biomedical applications such as wound healing products., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The ionic environment has a strong influence on the bioelectricity of skin, which is also present in the wound healing process. Inspired by this, we proposed a mechanism for hydrogel-based dressings to respond to endogenous electric fields through exudate absorption and conducted a verification study using a typical hydrogel, namely, polyacrylamide and sodium alginate (PAM-SA) hydrogels, as an example. Theoretical calculations showed that the PAM-SA hydrogels could absorb and orient the various electrolytes of exudate in the hydrogel at the wound site, contributing to the reconstruction of the electric field at the wound site. During the treatment process, this effect significantly accelerated the healing process of the rat epidermis, which exceeded the conventional dressing in terms of healing speed and efficacy, and the wounds on the complete layer of rat skin (wound area: 1.13 cm 2 ) could be rapidly repaired within 10 days. Revealing the electrophysiological behavior of PAM-SA dressings during wound healing can help further improve the design model, the optimization concept, and development paths for the bioelectrical structures of modern dressings and bioelectrical stimulation in wound healing.

Wound healing is a complex biological process that can trigger inflammation and oxidative stress and impair myofibrillogenesis and angiogenesis. Several advanced wound-dressing nanocomposite materials have been designed to address these issues. Here, we designed a new multifunctional styrene-ethylene-butylene-styrene/silver nanowire (SEBS/AgNWs)-based nanocomposite film with antimicrobial, antioxidant, and anti-inflammatory properties to promote wound healing. The porous morphological structure of SEBS/AgNWs enhances their antimicrobial, antioxidant, and anti-inflammatory properties. SEBS/AgNWs significantly inhibited the growth of Staphylococcus aureus , methicillin-resistant Staphylococcus aureus , and Escherichia coli strains, effectively wiping out ABTS•+, DPPH•, hydrogen peroxide (H 2 O 2 ), and hydroxyl (•OH) radicals, showing their effective ROS-scavenging properties. It further showed significant antioxidant properties by increasing the levels of enzyme-like catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), while decreasing malonaldehyde (MDA) levels. Additionally, SEBS/AgNWs reduced the expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), while increasing levels of transforming growth factor- β (TGF-β), vascular endothelial growth factor-A (VEGF), and CD31 in wound healing. This suggests that applying a multifunctional nanoplatform based on SEBS/AgNWs could enhance wound healing and improve patient outcomes in wound care management.

With a surge in the number of accidents and chronic wounds worldwide, there is a growing need for advanced hemostatic and wound care solutions. In this regard, in situ forming hydrogels have emerged as a revolutionary biomaterial due to their inherent properties, which include biocompatibility, biodegradability, porosity, and extracellular matrix (ECM)-like mechanical strength, that render them ideal for biomedical applications. This review demonstrates the advancements of in situ forming hydrogels, tracing their evolution from injectable to more sophisticated forms, such as sprayable and 3-D printed hydrogels. These hydrogels are designed to modulate the pathophysiology of wounds, enhancing hemostasis and facilitating wound repair. The review presents different methodologies for in situ forming hydrogel synthesis, spanning a spectrum of physical and chemical cross-linking techniques. Furthermore, it showcases the adaptability of hydrogels to the dynamic requirements of wound healing processes. Through a detailed discussion, this article sheds light on the multifunctional capabilities of these hydrogels such as their antibacterial, anti-inflammatory, and antioxidant properties. This review aims to inform and inspire continued advancement in the field, ultimately contributing to the development of sophisticated wound care solutions that meet the complexity of clinical needs.

Inspired by the hierarchical structure of the skin, asymmetric porous hydrogel encapsulating vulcanized molecular brushes (VMB@APH) as multifunctional wound dressing has been integrally constructed. The as-obtained VMB@APH effectively combines the anti-bacterial adhesion, anti-infection, and pro-healing properties, which is of great significance for accelerating the recovery of infected wounds.

Most natural and synthetic polymers are promising materials for biomedical applications because of their biocompatibility, abundant availability, and biodegradability. Their properties can be tailored according to the intended application by fabricating composites with other polymers or ceramics. The incorporation of ceramic nanoparticles such as bioactive glass (BG) and hydroxyapatite aids in the improvement of mechanical and biological characteristics and alters the degradation kinetics of polymers. BG can be used in the form of nanoparticles, nanofibers, scaffolds, pastes, hydrogels, or coatings and is significantly employed in different applications. This biomaterial is highly preferred because of its excellent biocompatibility, bone-stimulating activity, and favourable mechanical and degradation characteristics. Different compositions of nano BG are incorporated into the polymer system and studied for positive results such as enhanced bioactivity, better cell adherence, and proliferation rate. This review summarizes the fabrication and the progress of natural/synthetic polymer-nano BG systems for biomedical applications such as drug delivery, wound healing, and tissue engineering. The challenges and the future perspectives of the composite system are also addressed.

Diabetic wounds are usually entangled in a disorganized and self-perpetuating microenvironment and accompanied by a prolonged delay in tissue repair. Sustained and coordinated microenvironment regulation and tissue regeneration are key to the healing process of diabetic wounds, yet they continue to pose a formidable challenge. Here we report a rational double-layered dressing design based on chitosan and a degradable conjugated polymer polydiacetylene, poly(deca-4,6-diynedioic acid) (PDDA), that can meet this intricate requirement. With an alternating ene-yne backbone, PDDA degrades when reacting with various types of reactive oxygen species (ROS), and more importantly, generates proliferative succinic acid as a major degradant. Inheriting from PDDA, the developed PDDA-chitosan double layer dressing (PCD) can eliminate ROS in the microenvironment of diabetic wounds, alleviate inflammation, and downregulate gene expression of innate immune receptors. PCD degradation also triggers simultaneous release of succinic acid in a sustainable manner, enabling long-term promotion on tissue regeneration. We have validated the biocompatibility and excellent performance of PCD in expediting the wound healing on both diabetic mouse and porcine models, which underscores the significant translational potential of this microenvironment-modulating, growth-promoting wound dressing in diabetic wounds care., Competing Interests: Competing interests The Authors declare no competing interest., (© 2024. The Author(s).)

Essential oils (EOs) are volatile secondary metabolites of natural plants with multitudinous pharmacological activities. However, limited by their properties, such as low solubility, high volatility, photothermal instability, irritation, release, etc., EOs encounter significant challenges in pharmaceutical applications. Deep eutectic solvents (DESs) have been developed for the transdermal delivery of biomolecules and lipid-soluble drugs. Herein, a series of DES carriers were synthesized to improve the undesirable properties of EOs. We first optimized the DESs according to solubilization and aqueous dispersity using Chimonanthus nitens Oliv. EO (COEO) as a model EO. Then, the EO-DES formulations were diluted to prepare optimal aqueous EO-DES nanoformulations (AqEDs). Mechanically, hydrogen bonding allowed the DES to dissolve the complex components in EOs; meanwhile, the interaction forces, such as π - π stacking and hydrogen bonding, drove the EO-DES to assemble into nanostructures in aqueous conditions, forming AqEDs. Lastly, a case study demonstrated that clove EO-AqEDscould effectively promote methicillin-resistant Staphylococcus aureus -infected wound healing in vivo , along with biocompatibility. This AqED strategy provides a generalized platform for solubilizing EOs and improving their transdermal/topical delivery.

Chronic diabetic wounds suffer from severe complications caused by long-term high levels of oxidative stress and bacterial infection. Quercetin (Que) has excellent anti-inflammatory, antioxidant, and antibacterial activity, making it a promising drug to address the above issues. To exploit the benefits of Que in a more effective and sustained way to treat diabetic wounds, carboxymethyl β-cyclodextrin (CMCD) was synthesized and conjugated to keratin, then complexed with Que to form Que@Ker-CMCD inclusion, followed by electrospinning with polyurethane (PU) to afford Que@Ker-CMCD/PU mats. The approach significantly enhanced water solubility, bioavailability, and sustained release of Que. Crucially, these mats exhibited robust antioxidant and antibacterial activities. Moreover, the mats fostered an environment conducive to cell proliferation, migration, angiogenesis, and re-epithelialization, pivotal processes in wound healing and remodeling. Consequently, a marked acceleration in remodeling chronic diabetic wounds was observed. In conclusion, this study introduces a novel therapeutic strategy that not only harnesses the multifaceted benefits of Que but also enhances its delivery and performance, offering a promising avenue for the effective treatment of chronic diabetic wounds.

Moisture loss, infection, and severe inflammatory reactions are the primary factors affecting burn wound healing and leading to scar formation. Herein, we developed a quercetin-loaded polysaccharide-based injectable hydrogel (named PECE). The PECE consists of oxidized sodium alginate (OAlg) coupled with chitosan (CS) via Schiff bases and electrostatic interactions, while Que is incorporated via hydrogen bonding. Benefiting from the hydroxyl and carboxyl groups, PECE features distinguished moisturizing ability. Additionally, the sustained release of Que imparts remarkable antibacterial activity against Escherichia coli and Staphylococcus aureus . Likewise, PECE demonstrates favorable in vitro anti-inflammatory capacity as released Que significantly downregulates pro-inflammatory factors (IL-6 and TNF-α) secreted by RAW 264.7 macrophages. More importantly, in a rat model of deep second-degree burn wounds, PECE effectively inhibits wound infection, reduces inflammation, and promotes angiogenesis and collagen deposition, ultimately minimizing scar formation. Overall, this work presents a promising strategy for scarless healing of burn wounds.

The development of novel wound dressings is critical in medical care. Graphene and its derivatives possess excellent biomedical properties, making them highly suitable for various applications in medical dressings. This review provides a comprehensive technical analysis and the current application status of graphene-based medical dressings. Initially, we discuss the chemical structure and the fabrication method of graphene and its derivatives. We then provide a detailed summary of the mechanisms by which graphene materials promote wound repair across the four stages of wound healing. Subsequently, we categorize the types of graphene-based wound dressings and analyze corresponding characteristics. Finally, we analyze the challenges encountered at present and propose solutions regarding future development trends. This paper aims to serve as a reference for further research in skin tissue engineering and the development of innovative graphene-based medical dressings.