Endometrial injury and resulting female infertility pose significant clinical challenges due to the notable shortcomings of traditional treatments. Herein, we proposed a double network composite hydrogel, CSMA-RC-Zn-PNS, which forms a physical barrier on damaged tissue through photo-crosslinking while enabling sustained release of the active ingredient PNS. Based on this, we developed a combined strategy to enhance transdermal delivery efficiency using ultrasound cavitation. In vitro experiments demonstrated that CSMA-RC-Zn-PNS exhibits excellent biosafety, biodegradability, and promotes cell proliferation, migration, and tube formation, along with antioxidant and antibacterial properties. In a rat endometrial injury model, the ultrasound cavitation effect was demonstrated to enhance transdermal delivery efficiency, and the ability of CSMA-RC-Zn-PNS to promote endometrial regeneration, anti-fibrosis and fertility restoration was verified. Overall, this strategy combining CSMA-RC-Zn-PNS hydrogel and ultrasound treatment shows promising applications in endometrial regeneration and female reproductive health.

Several traditional dressings may have limitation in treating wounds. A novel chitosan-based dressing designed for improved hemostasis, moisture, and sealing shows promise in wound healing. However, its efficacy and safety are yet to be sufficiently verified in patients.

This randomized controlled trial enrolled 40 patients suffering from acute skin wounds in the limbs from 12/2022 to 12/2023. They were randomly divided into two groups (20 vs. 20) and received regular treatments in the Shenzhen Second People's Hospital. The experimental group was treated with chitosan-based liquid dressing, whereas the control group was treated with traditional dressing with recombinant human epidermal growth factor (rhEGF). The therapeutic effects (scar area and pigment deposition), adverse events, visual analogue scale (VAS), healing time, cost, and the patient and observer scar assessment scale (POSAS) were evaluated on days 0, 7, 14, and 28.

No adverse events were observed throughout the trial. On day 28, effective rate between groups were not statistically significant between the groups (70% vs. 85%, p = 0.256). Other parameters that were not significant included VAS (5.10 ± 1.62 vs. 6.35 ± 2.39, p = 0.06), healing time (8.45 ± 4.26 vs. 8.60 ± 5.44 days, p = 0.923), and cost (49.00 ± 22.48 vs. 57.40 ± 27.59, p = 0.298). However, on day 28, the patient- and observer-reported SAS of the chitosan (CS) group was significantly lower than that of the rhEGF group (12.00 vs. 9.50, z = 2.477, p = 0.013; 18.50 vs. 12.50, z = 2.209, p = 0.026; respectively), and the total POSAS (30.50 vs. 22.00, z = 2.374, p = 0.017).

Compared to rhEGF, the CS-based liquid dressing showed reliable safety and equivalent performance in treating acute limb skin wounds, as revealed by improvements in healing time and rate, pain relief, and costs. Moreover, liquid dressing significantly reduced scar formation, indicating its potential in wound therapy.

The treatment of chronic wounds presents significant challenges due to the necessity of accelerating healing within complex microenvironments characterized by persistent inflammation and biochemical imbalances. Factors such as bacterial infections, hyperglycemia, and oxidative stress disrupt cellular functions and impair angiogenesis, substantially delaying wound repair. Nanozymes, which are engineered nanoscale materials with enzyme-like activities, offer distinct advantages over conventional enzymes and traditional nanomaterials, making them promising candidates for chronic wound treatment. To enhance their clinical potential, nanozyme-based catalytic systems are currently being optimized through formulation advancements and preclinical studies assessing their biocompatibility, anti-oxidant activity, antibacterial efficacy, and tissue repair capabilities, ensuring their safety and clinical applicability. When integrated into multifunctional wound dressings, nanozymes modulate reactive oxygen species levels, promote tissue regeneration, and simultaneously combat infections and oxidative damage, extending beyond conventional enzyme-like catalysis in chronic wound treatment. The customizable architectures of nanozymes enable precise therapeutic applications, enhancing their effectiveness in managing complex wound conditions. This review provides a comprehensive analysis of the incorporation of nanozymes into wound dressings, detailing fabrication methods and emphasizing their transformative potential in chronic wound management. By identifying and addressing key limitations, we introduce strategic advancements to drive the development of nanozyme-driven dressings, paving the way for next-generation chronic wound treatments.

Oral ulcer (OU) is a highly prevalent mucosal disease characterized by persistent epithelial disruption. The primary challenge in its prolonged healing process is the disorder of re-epithelialization. This study develops a self-assembled hydrogel platform based on the natural small molecule rutin, which overcomes the re-epithelialization barrier through the synergistic effects of early growth response factor 1 (EGR1) gene programming and microenvironment remodeling. In this hydrogel, rutin formed supramolecular structures via hydrogen bonds and π-π interactions without structural modification. In vitro experiments confirm that rutin-based self-assembled hydrogel (RUTG) possesses excellent sustained-release properties and biocompatibility. Moreover, RUTG specifically regulates the transcriptional activation and translation of EGR1, thereby mediating the expression of re-epithelialization-related protein SOX9, and ultimately accelerating cell proliferation and migration as well as promoting re-epithelialization. Additionally, RUTG demonstrates beneficial anti-inflammatory and antioxidant properties, effectively remodeling the local microenvironment. In vivo studies using an oral ulcer model further confirm that RUTG could significantly accelerate the re-epithelialization process, shorten the ulcer healing cycle, and achieve functional tissue reconstruction. Collectively, this carrier-free hydrogel system, which integrates gene programming with microenvironment modulation to achieve efficient re-epithelialization, holds promise for introducing novel approaches to the treatment of oral ulcers.

Chronic non-healing wounds represent a growing global health challenge that is poorly addressed by current advances in wound care dressings. Hyperosmotic stress linked, for example, to poor glycaemic control, is a known but under-investigated contributor to the chronic wound environment and a known inflammatory stimulus. MXene (Ti3C2Tx) has been considered for smart dressing applications but has not been investigated for use with bioactive agents to directly moderate hyperosmotic stress for improved wound care. In this study, Ti3C2Tx, in combination with osmolyte betaine, was used to investigate hyperosmotic stress-induced effects on wound closure. The effect of these materials was measured using a wound closure scratch assay, and data was used to mathematically model changes in HaCaT human keratocyte migratory rate and velocity. Changes in the upregulation of apoptotic and inflammatory markers were measured, and qualitative changes in phalloidin-labelled actin cytoskeletal structure were observed. A tert-butyl glycine betainate (tBu-GB) polyacrylate microgel loaded Ti3C2Tx dressing was then fabricated and tested for biocompatibility and slow elution of osmolyte over time. Osmotic stress at levels that did not induce cell death reduced the migratory capacity of keratocytes to close the scratch. Migration by osmotically stressed keratocytes was reduced by more than 50% at 24 h and remained at 65% (±5%) at 48 h compared to complete scratch closure at 24 h in the cell only control. This reduction was reversed by a Ti3C2Tx coating, allowing complete scratch closure by 48 h in the osmotically stressed group. Exposure of osmotically stressed cells to betaine increased normalised wound closure in the osmotically stressed keraotycte group at each time point and this was augmented by the presence of a Ti3C2Tx coating. Osmotic stress induced upregulation of inflammatory markers IL-6, IL-1α, IL-1β, CXCL1, and CXCL8 by at least 10-fold. The effect was significantly greater in the presence of bacterial LPS and this was significantly reduced by the presence of Ti3C2Tx alone and in combination with betaine. Sustained and slow release of betaine was demonstrated from a tBu-GB-microgel loaded Ti3C2Tx dressing over 48 h supporting the use of such dressings to improve osmotic stress induced, poor wound closure rates.

The dysfunction of wound-healing processes can result in chronic non-healing wounds and pathological scar formation. Current treatment options often fall short, necessitating innovative approaches. Exosomes, extracellular vesicles secreted by various cells, have emerged as promising therapeutic agents serving as an intercellular communication system. By engineering exosomes, their cargo and surface properties can be tailored to enhance therapeutic efficacy and specificity. Engineered exosomes (eExo) are emerging as a favorable tool for treating non-healing wounds and pathological scars. In this review, we delve into the underlying mechanisms of non-healing wounds and pathological scars, outline the current state of engineering strategies, and explore the clinical potential of eExo based on preclinical and clinical studies. In addition, we address the current challenges and future research directions, including standardization, safety and efficacy assessments, and potential immune responses. In conclusion, eExo hold great promise as a novel therapeutic approach for non-healing wounds and non-healing wounds and pathological scars. Further research and clinical trials are warranted to translate preclinical findings into effective clinical treatments.

Subconjunctival injuries represent significant clinical challenges due to the complexities of post-injury inflammation and subsequent fibrosis, which lead to vision impairment; however, currently, no clinical interventions are available to resolve this problem. In this work, a novel dual drug-loaded core-shell nanofiber membrane based on two corn derivatives was fabricated via coaxial electrospinning to address this unmet clinical need. The nanofiber structure, comprising a polylactic acid shell and a zein core, sequentially released two natural products, rutin and celastrol. The rutin loaded in the polylactic acid shell was rapidly released to produce anti-inflammatory effects, whereas the celastrol loaded in the zein core was slowly released in the later stage to inhibit subconjunctival fibrosis. The in vitro results indicated that this nanofiber membrane platform significantly decreased the secretion of key proinflammatory cytokines and fibrosis biomarkers and reduced the risk of early bacterial invasion. Moreover, the in vivo results revealed that this platform not only ameliorated inflammation but also inhibited late-stage fibrosis, suggesting a promising therapeutic strategy. This study provides an effective exploration of a controlled and safe drug delivery platform, serving as a reference for effective interventions in other related diseases.

The skin acts as a vital barrier against external threats and regulates moisture levels. The skin's repair and rejuvenation encompass complex molecular and cellular mechanisms, constituting an essential yet intricate process to preserve skin integrity following trauma or surgical intervention. Acute wound repair unfolds through different interrelated stages, whereas chronic wounds pose significant healthcare challenges, often linked to conditions like diabetes and vascular diseases. Understanding of wound physiology is crucial for developing effective treatments. Chronic wounds require more comprehensive treatments, including surgical debridement, glycemic control, and antibiotic therapy. Ascorbic acid (AA) emerges as a promising wound-healing agent because it facilitates collagen synthesis, enhances antioxidant defense, promotes re-epithelialization and angiogenesis, regulates pH, and exhibits antimicrobial properties. Research outcomes on applying AA-based formulations on wound environment demonstrated its potential to accelerate wound closure and tissue regeneration, offering hope for improved wound management and reduced healthcare burdens associated with chronic wounds. The application of AA, which often utilizes innovative delivery methods and synergistic combinations with other actives, shows promise in preclinical studies for superior efficacy, biocompatibility, and controlled release profiles. Overall, AA-based therapies represent a significant avenue for advancing wound care and addressing the challenges of chronic wounds in healthcare systems.

Global public health faces a major danger from chemical and biological weapon-related terrorism which requires comprehensive emergency preparedness and response strategies. This review investigates present-day public health measures against bioterrorism by focusing on an all-hazards framework which unifies traditional and nontraditional threats. The review evaluates federal programs that boost state and local health systems through funding, distribution and team-based partnerships and technological innovation. The primary emergency response elements consist of identifying outbreaks early and improving surveillance together with using state-of-the-art diagnostic tools to detect biological and chemical agents. The review emphasizes the necessity of maintaining healthcare provider education alongside preparations of full medical readiness plans as well as strategic approaches for safeguarding defenseless groups. This paper investigates resource constraints and governmental agency coordination challenges during biowarfare emergencies. The review examines nucleic-acid-based diagnostic and sensor network innovations as vital components for real-time biological agent detection systems. The review emphasizes the vital role of community involvement together with psychological resistance training in addition to continued pathogen behavior study and protection research. The review demonstrates that successful bioterrorism risk reduction depends on advanced integrated protection strategies which combine state agency collaboration with state of the art monitoring techniques and strengthened public health systems.

Hypoxia, excessive reactive oxygen species (ROS), and an impaired inflammatory microenvironment are key barriers to diabetic wound healing, collectively hindering cell migration, proliferation, and neovascularization, ultimately leading to failure in the healing process. Therefore, developing an effective therapeutic strategy capable of simultaneously addressing these challenges remains a critical clinical need. In this study, we developed CeS-Gel, an advanced hydrogel dressing integrating live microalgae and CeO₂ nanoparticles within a dual-crosslinked silk hydrogel network. By harnessing photosynthesis, CeS-Gel provided a continuous and reliable oxygen supply, significantly enhancing cell migration and proliferation. Additionally, CeS-Gel exhibited potent ROS-scavenging properties, effectively mitigating oxidative stress-induced cellular damage while directly promoting M2 macrophage polarization, thereby modulating the inflammatory response. In vivo experiments demonstrated that CeS-Gel markedly accelerated wound healing in diabetic mice, achieving a 93.2 % wound closure rate. Furthermore, CeS-Gel effectively alleviated hypoxia, promoted neovascularization, and exhibited anti-inflammatory and immunoregulatory effects. This living microalgae-silk gel represents a promising approach for improving chronic diabetic wound healing with great potential for clinical application.

Photobiomodulation (PBM) has emerged as a promising method for enhancing wound healing. However, a standardized therapeutic protocol has not yet been established. This study aimed to determine the optimal irradiation parameters for wound healing in pigmented hairless mice (SKH-hr2). Mice were irradiated daily with energy doses of 2 or 4 J/cm2, achieved with different power densities in each group: 20, 50, or 100 mW/cm2. Various methods were used to evaluate the therapeutic efficacy, including histopathological analysis, clinical observation, photo-documentation, assessment of biophysical skin parameters, and Fourier Transform infrared (FT-IR) spectroscopy. The results indicated that the most favorable outcomes regarding wound healing acceleration and inflammation reduction were achieved with an irradiation setting of 50 mW/cm2 and 2 J/cm2. However, the group subjected to prolonged irradiation times with a power density of 20 mW/cm2 and energy of 4 J/cm2 exhibited subcutaneous bleeding. The FT-IR spectral absorption bands of amide groups provided important molecular-level information about the secondary structure of collagen, particularly in relation to skin regeneration and the response to applied energy, in agreement with histological data. This study highlights the critical need for further investigation into the parameters of photobiomodulation to ensure its effective application to the different skin phototypes and to mitigate potential adverse effects arising from incorrect usage.

Significance: Nonhealing or chronic wounds represent a significant and growing global health concern, imposing substantial burdens on individuals, health care systems, and economies worldwide. Although the standard-of-care treatment involves the application of wound dressings, most dressing materials are not specifically designed to address the pathological processes underlying chronic wounds. This review highlights recent advances in biomaterial design tailored to chronic wound healing. Recent Advances: Chronic wounds are characterized by persistent inflammation, impaired granulation tissue formation, and delayed re-epithelialization. Newly developed designer materials aim to manage reactive oxygen species and extracellular matrix degradation to suppress inflammation while promoting vascularization, cell proliferation, and epithelial migration to accelerate tissue repair. Critical Issues: Designing optimal materials for chronic wounds remains challenging due to the diverse etiology and a multitude of pathological mechanisms underlying chronic wound healing. While designer materials can target specific aberrations, designing a materials approach that restores all aberrant wound-healing processes remains the Holy Grail. Addressing these issues requires a deep understanding of how cells interact with the materials and the complex etiology of chronic wounds. Future Directions: New material approaches that target wound mechanics and senescence to improve chronic wound closure are under development. Layered materials combining the best properties of the approaches discussed in this review will pave the way for designer materials optimized for chronic wound healing.

Electrical stimulation (ES) serves as a biological cue that regulates critical cellular processes, including proliferation and migration, offering an effective approach to accelerating wound healing. Thermoelectrics, capable of generating electricity by exploiting the temperature difference between skin and the surrounding environment without external energy input, present a promising avenue for ES-based therapies. Herein, we developed Ag2Se@gelatin methacrylate (Ag2Se@GelMA) thermoelectric hydrogels with high room-temperature thermoelectric performance and employed them as self-powered ES devices for wound repair. Systematic in vivo and in vitro investigations elucidated their biological mechanisms for enhancing wound healing. Our findings reveal that the Ag2Se@GelMA thermoelectric hydrogels can significantly accelerate the wound closure by amplifying the endogenous electric field, thereby promoting cell proliferation, migration, and angiogenesis. Comprehensive in vitro experiments demonstrated that ES generated by the hydrogels activates voltage-gated calcium ion channels, elevating intracellular Ca2+ levels and enhancing mitochondrial functions through the Ca2+/CaMKKβ/AMPK/Nrf2 pathway. This cascade improves mitochondrial dynamics and angiogenesis, thereby accelerating tissue regeneration. The newly developed Ag2Se@GelMA thermoelectric hydrogels represent a marked progress in wound dressing technology with the potential to improve clinical strategies in tissue engineering and regenerative medicine.

The importance of electrospun membranes for biomedical applications has increased, especially when it comes to skin regeneration and wound healing. This review presents the production and applications of electrospun membranes based on polyurethane (PU) and silk fibroin (SF) and highlights their benefits as a skin substitute. This review also highlights the electrospinning technique used to prepare nanofibers for these biomedical applications. Silk, well-known for its excellent biocompatibility, biodegradability, structural properties, and low immunogenic response, is extensively investigated by addressing its molecular structure, composition, and medical uses. PU is a candidate for potential biomedical applications because of its strength, flexibility, biocompatibility, cell-adhesive properties, and high resistance to biodegradation. PU combined with silk offers a number of enhanced properties. The study offers a comprehensive overview of the advanced developments and applications of PU/SF composites, highlighting their significant potential in wound healing. These composite membranes present promising advancements in wound healing and skin regeneration by combining the unique properties of silk and PU, opening up the possibilities for innovative treatments.

Oxygen anions (superoxide and peroxide anions) are naturally unstable and prone to chemical interactions. These reactive oxygen species (ROS) are formed during long-term storage in olive oil (OO), the structural properties of which extend the ROS lifespan more effectively than those of other vegetable oils. In wound treatment, superoxide anions serve as precursors for hydrogen peroxide and play a crucial role in cell proliferation, migration, and angiogenesis. These anions were encapsulated within the OO medium for crystallization. Piezoelectric actuators were employed to distribute the trapped bubbles evenly throughout the crystallized OO. The ROS-filled OO microcapsules eliminated volatile organic compounds and particulate matter (from the air). Samples stored in crystallized OO were utilized to investigate the antibacterial effects. Both Escherichia coli and Staphylococcus aureus were implicated in skin infections (with S. aureus as the primary pathogen and E. coli as the secondary pathogen) and were selected for antibacterial testing. Microcapsules applied to cultured E. coli and S. aureus resulted in different inhibition zones. Two groups [control (C-) and treatment (T-)] of second-degree burn wounds were created on the dorsal area of 15 Wistar rats. Over a period of 2 weeks, statistical analysis using a t-test demonstrated a significant reduction in the wound size in the T-zones. Histological examination with hematoxylin, eosin, and trichrome staining of tissue samples from the wound areas revealed a notable reduction in inflammation, enhanced epidermal cell proliferation, improved activity in producing hair follicles, and increased collagen deposition in the treated regions on different days of observation.

High incidence and mortality rates of chronic wounds place a heavy burden on global healthcare systems. Achieving phased delivery of antimicrobial and regenerative drugs is crucial for promoting chronic wound healing. Herein, a microneedle (MN) patch with a biphasic release system was developed using a combination of solvent casting and spraying methods. Additionally, a copper/PDMS mold was introduced to address the issue of deformation in the chitosan material during drying on polydimethylsiloxane (PDMS). The MNs have a bilayer structure, with a hyaluronic acid (HA) coating loaded with doxycycline (DOX) for antibacterial action and a chitosan (CS) core loaded with vascular endothelial growth factor (VEGF) for promoting cell migration and proliferation. Notably, in vitro drug release studies showed that the coating drug was released by 98.8% within 10 hours, while the release of the core drug could be sustained for up to 70 hours. In vivo studies showed that chronic wounds on C57 mice treated with CS/HA-bilayer MNs achieved nearly complete healing by day 9. These wounds exhibited reduced inflammatory cell infiltration, increased epithelial tissue regeneration, and enhanced collagen deposition. This work integrates the staged management of bacterial infection and angiogenesis and offers promising prospects for enhancing chronic wound healing.

Effective modulation of persistent inflammation is crucial for chronic wound healing. However, the interaction cascade between inflammatory factors and immune cells at the soft-tissue wound interface poses an incredible challenge for this purpose. Here, we report an immunosuppressive pure DNA hydrogel (Is-pDNAgel) that reprograms inflammatory responses from both molecular and cellular dimensions. Specifically, high-density negative charges enable Is-pDNAgel to efficiently scavenge free chemokines, mitigating neutrophil and macrophage infiltration. Moreover, its immunosuppressive domain synergistically acts on activated residual immune cells and suppresses multiple proinflammatory signaling pathways, thereby creating a positive circuit to boost anti-inflammatory efficacy. Is-pDNAgel can further facilitate migration and proliferation of endogenous endothelial cells owing to its intrinsic extracellular matrix-mimicking structure, promoting re-epithelialization and neovascularization for tissue regeneration without additional bioactive components. Such an "all-in-one" hydrogel outperforms a commercial dressing to accelerate the healing of chronic wounds in a diabetic mouse model, offering a valuable tool for developing regenerative medicine.

Effective immune homeostasis modulation and re-epithelialization promotion are crucial for accelerating burn wound healing. Cell migration is fundamental to re-epithelialization, with epithelial-mesenchymal transition (EMT) as a key mechanism. A sustained inflammatory environment or impaired macrophage transition to M2 phenotype can hinder pro-resolving cytokine activation, further delaying the recruitment, migration, and re-epithelialization of epidermal cells to the injury site, ultimately compromising wound healing. Herein, the bioactive flavonol quercetin is transformed into pharmacologically active carbonized polymer dots (Qu-CDs) spray with high water dispersibility, permeability and biocompatibility for full-thickness skin burns treatment. Qu-CDs spray can efficiently initiate macrophage reprogramming and promote the transition of macrophages from M1 to M2 phenotype, modulating immune responses and facilitating the shift from the inflammatory phase to re-epithelialization. Additionally, Qu-CDs spray can promote cell migration and re-epithelialization of wound edge epithelial cells by inducing an EMT process without growth factors, further accelerating the reconstruction of the normal epidermal barrier. Mechanistically, Qu-CDs spray activates the smad1/5 signaling pathway for promoting the EMT phenotype of wound edge epithelial cells. Overall, this study facilitates the construction of novel spray dosage form of pharmacologically active carbonized polymer dots with desired bioactivities for effective wound healing.

Diabetic wounds are refractory and recurrent diseases that necessitate the development of multifunctional dressings. Inspired by the structure and function of the skin, we herein delicately design a novel swollen hydrophobic hydrogel (QL@MAB) composed of hydrophobic methyl acrylate (MA) and (3-acrylamidophenyl)boronic acid (AAPBA) network and co-loaded with antioxidant quercetin (Q) and antibiotic levofloxacin (L) for efficient diabetic wound therapy. The hydrophobic MA segments undergo phase separation to form a dense "epidermis", ensuring prolonged drug diffusion, long-term water retention, and high water content. Meanwhile, the AAPBA segments generate glucose-labile "sweat pores" via borate ester bonds with the polyphenol drug Q. Upon encountering the hyperglycemic wound microenvironment, the "sweat pores" are dilated due to the cleavage of the borate ester bonds and exposure of the diffusion channel, facilitating drug release for accelerated wound healing. In the infected diabetic rats, QL@MAB achieves rapid wound debridement and re-epithelization while promoting angiogenesis, hair follicle regeneration, and extracellular matrix remodeling. Taken together, this study not only represents a multipronged dressing for effective interventions of diabetic wounds but also contributes to the rational design of smart hydrogels tailored for biomedical applications.

Despite advances in wound treatment through tissue engineering, the rapid colonization of biomaterials by host cells remains a crucial step toward complete wound healing. Thanks to their excellent biocompatibility, biodegradability, low antigenicity and cost-effectiveness, cross-linked hydrogels have attracted much attention as a viable solution for wound treatment. In this work, we have developed an inovative cross-linking method for gelatin-based hydrogels inspired by the wound closure mechanism of the green algae Caulerpa taxifolia. Caulerpenyne (CYN), a metabolite extracted from the algae, was used as a latent cross-linking agent for gelatin. The covalent cross-linking process is triggered by an in situ and on-demand deacetylation of the enol acetate functionalities of CYN in oxytoxin 2 (OXY) containing 1,4-dialdehyde, which immediately reacts with the lysine residue in gelatin. The content of ε-amino groups in gelatin was monitored as a function of CYN concentration. Swelling and gel content were analyzed as a function of CYN concentration. Morphology, rheological and biological properties were evaluated by in vitro and in vivo tests. Cell adhesion and viability tests performed with OXY-cross-linked hydrogels and compared with non-cross-linked and genipin-cross-linked gelatin showed excellent performance. Their use in whole skin wounds in pigs showed that CYN-cross-linked hydrogels promoted complete skin regeneration without any cytotoxicity, making them extremely promising matrices in the field of regenerative medicine.

In the field of wound treatment, chronic wounds pose a significant burden on the medical system, affecting millions of patients annually. Current treatment methods often fall short in promoting effective wound healing, highlighting the need for innovative approaches. Electrospinning, a technique that has garnered increasing attention in recent years, shows promise in wound care due to its unique characteristics and advantages. Recent studies have explored the use of electrospun nanofibers in wound healing, demonstrating their efficacy in promoting cell growth and tissue regeneration. Researchers have investigated various materials for electrospinning, including polymers, ceramics, carbon nanotubes (CNTs), and metals. Hydrogel, as a biomaterial that has been widely studied in recent years, has the characteristics of a cell matrix. When combined with electrospinning, it can be used to develop wound dressings with multiple functions. This article is a review of the application of electrospinning technology in the field of wound treatment. It introduces the current research status in the areas of wound pathophysiology, electrospinning preparation technology, and dressing development, hoping to provide references and directions for future research.

Achieving scar-free skin regeneration in clinical settings presents significant challenges. Key issues such as the imbalance in macrophage phenotype transition, delayed re-epithelialization, and excessive proliferation and differentiation of fibroblasts hinder wound healing and lead to fibrotic repair. To these, we developed an active shrinkage and antioxidative hydrogel with biomimetic mechanical functions (P&G@LMs) to reshape the healing microenvironment and effectively promote skin regeneration. The hydrogel's immediate hemostatic effect initiated sequential remodeling, the active shrinkage property sealed and contracted the wound at body temperature, and the antioxidative function eliminated ROS, promoting re-epithelialization. The spatiotemporal release of LMs (ACEI) during the inflammation phase regulated macrophage polarization towards the anti-inflammatory M2 phenotype, promoting progression to the proliferation phase. However, the profibrotic niche of macrophages induced a highly contractile α-SMA positive state in myofibroblasts, whereas the sustained LMs release could regulate this niche to control fibrosis and promote the correct biomechanical orientation of collagen. Notably, the biomimetic mechanics of the hydrogel mimicked the contraction characteristics of myofibroblasts, and the skin-like elastic modulus could accommodate the skin dynamic changes and restore the mechanical integrity of wound defect, partially substituting myofibroblasts' mechanical role in tissue repair. This study presents an innovative strategy for skin regeneration.

Diabetic foot ulcer (DFU) is a common and severe complication of diabetes mellitus, the etiology of which remains insufficiently understood, particularly regarding the involvement of extracellular vesicles (EVs). In this study, nanoflow cytometry to detect EVs in DFU skin tissues is used and found a significant increase in the Translocase of Outer Mitochondrial Membrane 20 (TOM20)+ mitochondrial-derived vesicles (MDVs). The role of MDVs in DFU is yet to be reported. Using single-cell datasets, it is discovered that the increase in MDVs may be regulated by Sorting Nexin 9 (SNX9). In vitro experiments revealed that MDVs secreted by fibroblasts cultured in high glucose medium exhibited similar composition and protein enrichment results to those in DFU tissues, suggesting their potential as an ideal in vitro surrogate. These MDVs promoted apoptosis and intracellular oxidative stress, disrupted mitochondrial structure, and reduced aerobic metabolism in target cells. In vivo experiments also showed that MDV drops hindered wound healing in diabetic mice; however, this effect is rescued by SNX9 inhibitors, restoring mitochondrial dynamics and balance. Under high glucose conditions, MDVs significantly upregulated oxidative stress levels and induced mitochondrial dysfunction. This study proposes targeting MDVs as a potential therapeutic strategy for DFU.

Wound healing in diabetic patients is often compromised due to excessive inflammation, oxidative stress, and impaired angiogenesis, leading to delayed recovery and increased susceptibility to complications. This study aimed to develop an emulgel formulation of guava leaf oil, derived from Psidium guajava (Myrtaceae), and evaluate its wound healing potential in nondiabetic and diabetic rats. Preliminary phytochemical analysis of guava leaf oil identified active compounds such as D-limonene, β-caryophyllene, and 1,8-cineole, which are known for their anti-inflammatory and antioxidant properties. The emulgel was formulated and assessed for physical attributes, including pH, viscosity, spreadability, and stability. The emulgel demonstrated potent antimicrobial activity, with the 1% concentration showing significant efficacy. In vivo studies revealed enhanced wound contraction in diabetic rats treated with the emulgel, supporting its role in promoting excision wound healing. These findings underscore the therapeutic potential of guava leaf oil emulgel as an effective agent for managing nondiabetic and diabetic wounds, providing a foundation for future clinical applications.

The aim of this study is to investigate the effect of the adhesive, conductive hydrogel on wound healing when used as a therapeutic dressing. Herein, a dressing of PVA/QCS/TP@Fe3+ (PQTF) was designed and prepared integrating polyvinyl alcohol (PVA), chitosan quaternary ammonium salt (QCS), tea polyphenol (TP), and ferric ions (Fe3+) by a simple one-pot and freeze-thaw method. In view of the comprehensive properties of PQTF600 hydrogel, including adhesion, electrical conductivity, and swelling performance, PQTF600 was selected for subsequent in vitro and in vivo healing promotion studies. PQTF600 had good adhesion and conductive ability, which was suitable for human motion monitoring and wound treatment. Notably, the PQTF600 showed and controllable human safety temperature thresholds (~44.8 °C) under near-infrared light (NIR). Meanwhile, PQTF600 achieved nearly 100 % antibacterial activity against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas putida (P. putida), methicillin-resistant Staphylococcus aureus (MRSA). In addition, the PQTF600 hydrogel dressing was demonstrated to achieve 99.59 ± 4.11 % would healing rate in a mouse trauma model under the dual stimulation of NIR (808 nm) and electricity (1.5 V direct current). The versatile PQTF600 hydrogel is a promising dressing for enhancing wound closure integrating with electrical stimulation (ES) and photothermal therapy.

Re-epithelialization constitutes a critical stage in the intricate process of wound healing, yet its mechanisms in the context of diabetic wounds remain elusive. In this study, the role of the mesenchymal-epithelial transition (MET) vis-à-vis the epithelial-mesenchymal transition (EMT) of keratinocytes in diabetic wound re-epithelialization is investigated. The findings reveal an impediment in the MET process, rather than EMT, which significantly compromised re-epithelialization in diabetic wounds. Furthermore, Desmoplakin (DSP) gene expression, encoding a key desmosome protein, is down-regulated in diabetic rats. This down-regulation coincided with aberrant hypo-demethylation of the DSP promoter. The inhibition of DSP expression is linked to reduced occupancy of Ten-eleven translocation 3 (TET3) at the DSP promoter, consequently suppressing TET3-dependent DNA demethylation. Additionally, a novel lncRNA termed DSP-AS1is identified, which is antisense to DSP. Notably, DSP-AS1 expression is down-regulated in diabetic skin wounds, and it interacted with TET3, a DNA demethylase. Notably, DSP-AS1 is found to form R-loops, triple-stranded DNA:RNA hybrids, at the DSP promoter, facilitating TET3 localization to the DSP promoter. Collectively, the findings suggest that reduced R-loop formation by DSP-AS1 impairs DSP gene transcription by repressing TET3-mediated DNA demethylation. This disruption of the orchestrated re-epithelialization process contributes to refractory diabetic wound healing.

Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay.

The copper complex of the tripeptide glycine-histidine-lysine (GHK) has proven benefits in wound healing and tissue remodeling by promoting blood vessel growth and increasing skin oxygen levels, but its activity is reduced in body fluids due to fast proteolytic cleavage. Herein, we designed several peptides that bear the GHK sequence and can self-assemble into supramolecular nanostructures aiming for enhanced bioactivity. The design involves a phenylalanine (F) backbone known for its ability to form supramolecular assemblies. We tested either coassembly between the structural peptide F4D and the functional sequence GHK or assembly of covalently bound peptides, in which the GHK is bound via the glycine (F4D-GHK) or lysine (F4D-KHG, i.e., inverted GHK sequence). All tested peptides assembled into nanotapes, but their resistance to proteolytic degradation was different: covalently bound peptides generated more stable assemblies. Wound healing assays demonstrated that the supramolecular structures have enhanced bioactivity when compared to GHK alone. Multiplex immunoassay analyses demonstrated the secretion of key regulators of the healing process, such as cytokines, matrix metalloproteinases, and growth factors. Altogether our data show that incorporation of GHK/KHG into supramolecular structures improves its stability, bioactivity, and efficacy in promoting wound healing.

In the field of plastic surgery, epidermal transplantation is a potential treatment for chronic wounds that results in only minor donor site morbidity. Improving the regenerative capacities of epidermal grafts or single-cell suspensions and therefore accelerating healing processes would be of significant interest.

In the present study, we analyzed the effects of growth factors and adipose-derived stem cells (ADSCs) on keratinocyte properties. For optimum translation into the clinical setting, primary human keratinocytes and patient-matched ADSCs were isolated and used in an in vitro wound model.

The keratinocyte migration and viability increased after treatment with the growth factors insulin-like growth factor 1 (IGF-1) and keratinocyte growth factor (KGF). A similar effect was observed with the use of a concentrated ADSC-conditioned medium (ADSC-CM). It was further possible to isolate the keratinocytes in a xenogen-free medium, which is essential for clinical translation. Importantly, a patient-dependent influence on the effects of the growth factors and ADSC-CM was observed.

This study provides potential for the improvement of epidermal transplantation in the treatment of chronic wounds using xenogen-free isolated and cultivated keratinocytes, growth factors, and ADSC. Translating these results into clinical application may help accelerate wound healing and shorten the time until patients can return to everyday life.

The dynamic, complex process of cutaneous wound healing is required to restore skin integrity following an injury. This intricate process consists of four sequential and overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Hemostasis immediately begins to function in response to vascular injury, forming a clot that stops the bleeding. To fight infection and remove debris, immune cells are enlisted during the inflammatory phase. Angiogenesis, re-epithelialization, and the creation of new tissue are all components of proliferation, whereas tissue maturation and scarring are the outcomes of remodeling. Chronic wounds, like those found in diabetic ulcers, frequently stay in a state of chronic inflammation because they are unable to go through these stages in a coordinated manner. The important regulatory roles that microRNAs (miRNAs) play in both normal and pathological wound healing have been highlighted by recent investigations. The miRNAs, small non-coding RNAs, modulate gene expression post-transcriptionally, profoundly impacting cellular functions. During the inflammatory phase, miRNAs control pro- and anti-inflammatory cytokines, as well as the activity of immune cells such as neutrophils and macrophages. Additionally, miRNAs are essential components of signaling networks related to inflammation, such as the toll-like receptor (TLR), nuclear factor kappa B (NF-kB), and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Some miRNAs have been discovered to either increase or alleviate inflammatory reactions, indicating their potential as therapeutic targets. Other miRNAs aid in angiogenesis by promoting the development of new blood vessels, which are essential for providing oxygen and nutrients to the healing tissue. They also affect keratinocyte migration and proliferation during the re-epithelialization phase, which involves growing new epithelial cells over the lesion. Another function of miRNAs is that they control the deposition of extracellular matrix (ECM) and the creation of scars during the remodeling phase. The abnormal expression of miRNAs in chronic wounds has led to the exploration of miRNA-based treatments. With a focus on resistant instances such as diabetic wounds, these therapeutic techniques seek to improve wound healing results by correcting the dysregulated miRNA expression.

In recent decades, chronic wounds have become an increasingly significant clinical concern because of their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of reepithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, the authors have identified the pharmacologic product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds.

The role of TT-10 in regulating YAP activity and subcellular localization was determined by Western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination; hematoxylin and eosin staining; and measuring wound areas and gaps in normal, diabetic, and ischemic wounds.

The authors' findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, the authors showed that intracutaneous injection of TT-10 along the wound periphery promoted reepithelialization by means of YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models.

The authors' research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

The authors' research identifies TT-10, a small molecule YAP activator, as a novel therapeutic candidate that enhances keratinocyte function and promotes reepithelialization, offering plastic surgeons an innovative approach to addressing chronic wound challenges.

Despite the advances in the development of therapeutic wearable wound-healing patches, lack self-healing properties and strong adhesion to diabetic skin, hindering their effectiveness. We propose a unique, wearable patch made from a 3D organo-hydrogel nanocomposite containing polydopamine, titanium dioxide nanoparticles, and silver quantum dots (PDA-TiO2@Ag). The designed patch exhibits ultra-stretchable, exceptional-self-healing, self-adhesive, ensuring conformal contact with the skin even during movement. Our patch demonstrated potent antibacterial activity and significantly accelerated wound healing with a high wound closure rate of 99.2 % after 7 days. Remarkably, it enhanced diabetic skin wound healing compared to that achieved by adipose-derived stem cell (ADSC) therapy in a study involving 30 adult male albino rats. Microscopic analysis highlights the promising hierarchical architecture structure of the patch for wound healing applications, suggesting its potential to create a favorable environment for healing and provide long-lasting benefits. Histopathological analysis and immunohistochemical staining revealed faster healing and enhanced cellular response in the patch-treated group compared to both stem cell and control groups. Notably, the patch promoted complete re-epithelization and a significant increase in vascular endothelial growth factor (VEGF) expression on day 7, indicating improved angiogenesis. This self-healing, multifunctional patch offers a promising alternative to stem cell therapy for accelerating diabetic wound healing, showcasing its potential for clinical translation. The combination of durability, biocompatibility, and antibacterial properties makes the patch a promising candidate for advanced wound management and offering faster, more complete restoration than other approaches.

Chronic wounds have emerged as a tough clinical challenge. An improved understanding of wound-healing mechanisms is paramount. Collagen XVII (COL17), a pivotal constituent of hemidesmosomes, holds considerable promise for regulating epidermal cell adhesion to the basement membrane as well as for epidermal cell motility and self-renewal of epidermal stem cells. However, the precise role of COL17 in wound repair remains elusive, and the upstream regulatory mechanisms involved have not been fully elucidated. In this study, we delineated the temporal and spatial expression patterns of COL17 at the epidermal wound edge. Subsequently, we investigated the indispensable role of COL17 in keratinocyte activation and reepithelialization during wound healing, demonstrating the restoration of the normal repair process by COL17 overexpression in diabetic wounds. Notably, we identified a key transcriptional signaling pathway for COL17, wherein pyruvate kinase isozyme M2 (PKM2) promotes phosphorylation of STAT3, leading to its activation and subsequent induction of COL17 expression upon injury. Ultimately, by manipulating this pathway using the PKM2 nuclear translocator SAICAR, we revealed a promising therapeutic strategy for enhancing the healing of chronic wounds.

In this study, an alginate/PEG hydrogel was developed via a thiol-Michael addition reaction between oxidized quinone of catechols on dopamine-grafted sodium alginate (SA-DA) and sulfhydryl groups of 4-arm polyethylene glycol tetra-thiol (4-arm PEG-SH) under mildly basic conditions. Through the formation of thiol-terminated catechol groups, the accompanying oxidized catechols are reduced, significantly strengthening the internal network structure of the hydrogel and improving tissue adhesion. Meanwhile, the hydrogels have excellent self-healing properties due to the dynamic non-covalent bonds between the groups. Adjustment of hydrogel properties by varying the mass ratio of two hydrogel precursors. Due to the high content of thiol-terminated catechol groups, the Gel 3 exhibited good tissue adhesion, rapid self-healing ability, and other multifunctions beneficial to wound healing, including killing of E. coli and S. aureus, rapid hemostasis and promoting migration of L929 cells. The full-thickness skin wound model shows that the hydrogel dressing significantly accelerated wound contraction, with increased granulation tissue thickness, collagen disposition, and enhanced vascularization, thus promoting wound healing. Therefore, the thiol-Michael addition reaction is an effective method for creating multifunctional hydrogels, and the injectable self-healing alginate/PEG hydrogels prepared in this way could be used in the biomedical area as wound healing dressing materials.

Aligned electrospinning membranes (Align) have demonstrated the potential to enhance wound healing by establishing a regenerative microenvironment surrounding the wound; However, the precise mechanism underlying its facilitation of healing remains unclear. To elucidate aligned electrospun fiber membrane's role in accelerating wound healing and improving its quality, we conducted a comprehensive analysis. Firstly, in vivo experiments confirmed that Align promotes wound healing. Through combined bulk RNA sequencing and single-cell RNA sequencing, we identified that MMP12+ macrophages exhibit high expression of MMP12 during the early stage of wound remodeling, thereby inhibiting fibroblast migration and reducing scar formation after wound closure. Finally, both in vitro and in vivo experiments further validated the role of MMP12 in promoting wound healing and suppressing fibroblast migration. Our findings reveal that Align effectively enhances skin wound healing by upregulating MMP12 expression while inhibiting fibroblast migration. These insights provide valuable knowledge on how Align promotes efficient scar-free wound healing and serve as a theoretical foundation for developing more effective biological dressings.

Despite significant progress in tissue engineering, the full regeneration of chronic wounds persists as a major challenge, with the immune response to tissue damage being a key determinant of the healing process's quality and duration. Post-injury, a crucial aspect is the transition of macrophages from a pro-inflammatory state to an anti-inflammatory. Thus, this alteration in macrophage polarization presents an enticing avenue within the realm of regenerative medicine. Recent advancements have entailed the integration of a myriad of cellular and molecular signals into hydrogel-based constructs, enabling the fine-tuning of immune cell activities during different phases. This discussion explores modern insights into immune cell roles in skin regeneration, underscoring the key role of immune modulation in amplifying the overall efficacy of wounds. Moreover, a comprehensive review is presented on the latest sophisticated technologies employed in the design of immunomodulatory hydrogels to regulate macrophage polarization. Furthermore, the deliberate design of hydrogels to deliver targeted immune stimulation through manipulation of chemistry and cell integration is also emphasized. Moreover, an overview is provided regarding the influence of hydrogel properties on immune traits and tissue regeneration process. Conclusively, the accent is on forthcoming pathways directed toward modulating immune responses in the milieu of chronic healing.