Promote Wound Healing Research Articles

Resolution of Non-Diabetic Intractable Wounds with Severe Comorbidities Using Autologous Micrografts

The wound healing process is a complex mechanism related to many factors, such as the patient’s comorbidity, blood flow, and nutritional status. This study aimed to retrospectively evaluate patients affected by various disease states and treated with Rigenera® technology, a standardized micrograft preparation system. A total of 8 patients were treated with a suspension of autologous micrografts obtained from mechanical disaggregation of small pieces of skin tissue. The micrografts suspension was applied alone to the wound or in combination with porcine collagen scaffolds directly onto the wound as described in the text. Across all cases, there was marked improvement in wound healing, with a mean healing time of 103 days and a reduction of the diameter of the wounds by 54%. Notably, the use of micrografts resulted in an overall higher quality of life for the patients. This simple and low-cost micrografting procedure that can promote wound healing of different kinds of chronic non-healing wounds and does not require postoperative rest.

Multifunctional SEBS/AgNWs Nanocomposite Films with Antimicrobial, Antioxidant, and Anti-Inflammatory Properties Promote Infected 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 (H2O2), 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.

Skin Temperature‐Activated Multifunctional Thermoelectric Dressing for Bacterial Infected Wound Treatment

AbstractEndogenous electric field (EEF) is weakened in wounds due to electrolyte loss, hindering wound repair. Reshaping and repairing EEF play important roles in accelerating wound healing. The design of antibacterial dressings coupled with an EEF recovery ability to promote wound healing is urgent and significant. Herein, a self‐powered wearable thermoelectric dressing with antibacterial, antioxidant, and EEF reshaping activities for methicillin‐resistant Staphylococcus aureus‐infected wound therapy is fabricated. The dressing is based on a wearable thermoelectric device constructed of a polyanionic thermoelectric hydrogel loaded with tannic acid (TA). By taking advantage of the natural temperature difference between infected wounds and the external environment, the dressing is activated to convert thermal energy into electricity, producing a continuous and compensating electric field to reshape damaged EEF and stimulate tissue regeneration. Combined with the antibacterial and antioxidant properties of the TA released from the thermoelectric hydrogel, the self‐powered dressing can accelerate wound healing in vivo by topical targeted sterilization, reducing inflammation and reshaping the EEF of the wounds. Thus, this dressing provides a promising and facile self‐powered therapeutic strategy without the need for external stimuli to treat infected wounds.

A wearable and stretchable dual-wavelength LED device for home care of chronic infected wounds.

Phototherapy can offer a safe and non-invasive solution against infections, while promoting wound healing. Conventional phototherapeutic devices are bulky and limited to hospital use. To overcome these challenges, we developed a wearable, flexible red and blue LED (r&bLED) patch controlled by a mobile-connected system, enabling safe self-application at home. The patch exhibits excellent skin compatibility, flexibility, and comfort, with high safety under system supervision. Additionally, we synthesized a sprayable fibrin gel (F-gel) containing blue light-sensitive thymoquinone and red light-synergistic NADH. Combined with bLED, thymoquinone eradicated microbes and biofilms within minutes, regardless of antibiotic resistance. Furthermore, NADH and rLED synergistically improved macrophage and endothelial cell mitochondrial function, promoting wound healing, reducing inflammation, and enhancing angiogenesis, as validated in infected diabetic wounds in mice and minipigs. This innovative technology holds great promise for revolutionizing at-home phototherapy for chronic infected wounds.

Usefulness of hot shot intermittent infusion online hemodiafiltration plus far-infrared therapy for dialysis patients with lower extremity arterial disease: a case report

BackgroundLower extremity arterial disease (LEAD) occurs at a high frequency in dialysis patients and is associated with a poor prognosis. In recent years, intermittent infusion online hemodiafiltration (I-OHDF) combined with far-infrared therapy (FIR) has been reported as being useful in dialysis patients with LEAD. However, there are also reports of worsening of the ulcers and gangrene in some cases. Hot shot I-OHDF (HS I-OHDF), which involves intermittent infusion of heated dialysate, is reported as being more effective than conventional I-OHDF for improving the plasma refilling rate (PRR) and peripheral circulation. We report the case of a patient in whom a lower extremity ulcer healed only after we switched from I-OHDF + FIR to HS I-OHDF + FIR, and the usefulness of this treatment.Case presentationThe patient was a 41-year-old male dialysis patient with LEAD who showed worsening of the ulcers in the lower extremity before he was switched from I-OHDF plus FIR to HS I-OHDF plus FIR; we compared the changes in the lower extremity blood flow, PRR, degree of wound healing, and subjective symptoms over time after the switch to HS I-OHDF plus FIR as compared with the values prior to the switching. As compared with the values during I-OHDF plus FIR, the lower extremity blood flow and PRR increased markedly during HS I-OHDF plus FIR. The wounds in the lower extremity improved over time during HS I-OHDF plus FIR and showed complete healing after 6 months; evaluation by visual analog scales (VASs) showed improved scores for all of fatigue, pain, coldness, and insomnia, and the patient reported improved subjective symptoms. The mechanism underlying the effectiveness of HS I-OHDF plus FIR in promoting wound healing is unknown, however, we speculated that the temperature change in the intermittent infusion solution resulted in increased blood flow in the true capillaries (resting vessels) and transfer of the nonthermal effects of FIR to more peripheral vessels.ConclusionsThis case demonstrates that combined use of HS I-OHDF with FIR can enhance the efficacy of FIR in dialysis patients with LEAD by increasing the lower extremity blood flow and PRR, which is useful for wound healing.

Topical Application of Melatonin in a Grapeseed Oil-based Microemulsion Accelerated Wound Healing in Rat Models

Objective: Melatonin has been associated with accelerated tissue regeneration and grapeseed oil has abundant unsaturated fatty acids, particularly linoleic acid that makes it a strong antioxidant, having the potential to promote wound healing by enhancing the presence of free radicals at the wound site. The study is aimed to evaluate the potential of a microemulsion gel using grapeseed oil as the organic phase and melatonin encapsulated in the vesicles to exhibit synergistic wound healing in Swiss albino rats. Materials and Method: Microemulsion containing grapeseed oil encapsulating melatonin was developed using the water-titration method. The surfactant and co-surfactant ratio (Smix) were fixed at 1:1. A pseudo-ternary diagram was used to determine the microemulsion zone and the developed microemulsion was further incorporated in carbopol 934P gel. The formulations were evaluated for their physicochemical properties and cytotoxicity assay. The optimized formulation was topically applied to cutaneous wounds of Swiss albino rat models. 30 Swiss albino rats were divided into five groups of 6 animals each: (i) Negative control group, (ii) Standard marketed formulation treated group, (iii) Optimized microemulsion containing Grapeseed oil and melatonin treated group, (iv) Grapeseed oil treated group and (v) Melatonin treated group. All the rats in each group were topically applied with the desired formulations daily for up to 14 days. Results: The treatment with a formulation comprising 10.18% Grapeseed oil, 24.88% water, and 64.94% Smix exhibited the highest entrapment efficiency of 86.65 ± 1.88% with an enhanced in vitro drug release of up to 83.02 ± 1.09%, also demonstrating first-order release kinetics. Furthermore, it did not inhibit L929 mouse fibroblast cell proliferation up to 500 μg/mL and promoted wound closure prior to other groups. Additionally, increased tissue maturation with higher collagen deposition was mostly seen by day 7. Thus demonstrating it is suitable for dermal application and sustained release of melatonin. The in vivo wound healing study and histological investigations on rat models demonstrated comparable results as observed in the marketed formulation of melatonin. Conclusion: The results showed that GSO oil based microemulsion encapsulating MEL could be a promising wound treatment option to exhibit accelerated wound healing effects.

Development of phage-containing hydrogel for treating Enterococcus faecalis-infected wounds.

Chronic wound infections caused by Enterococcus faecalis pose formidable challenges in clinical management, exacerbated by the emergence of vancomycin-resistant strains. Phage therapy offers a targeted approach but encounters delivery hurdles. Due to their biocompatibility and controlled release properties, hydrogels hold promise as carriers. This study aimed to fabricate phage-containing hydrogels using sodium alginate (SA), carboxymethyl cellulose (CMC), and hyaluronic acid (HA) to treat E. faecalis-infected wounds. We assessed the efficacy of these hydrogels both in vitro and in vivo. The hydrogel was prepared using SA-CMC-HA polymers. Phage SAM-E.f 12 was incorporated into the SA-CMC-HA hydrogel. The hydrogel's swelling index was measured after 24 h, and degradation was assessed over seven days. Surface morphology and composition were analyzed using Scanning Electron Microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Antibacterial activity was tested via optical density (OD) and disk diffusion assays. Phage release and stability were evaluated over a month. In vivo efficacy was tested in mice through wound healing and bacterial count assays, with histopathological analysis. Hydrogels exhibited a swelling index of 0.43, a water absorption rate of %30, and 23% degradation over seven days. FTIR confirmed successful polymer incorporation. In vitro studies demonstrated that phage-containing hydrogels significantly inhibited bacterial growth, with an OD of 0.3 compared to 1.1 for the controls. Hydrogels remained stable for four weeks. In vivo, phage-containing hydrogels reduced bacterial load and enhanced wound healing, as shown by improved epithelialization and tissue restoration. Phage-containing hydrogels effectively treat wounds infected with E. faecalis-infected wounds, promoting wound healing through controlled phage release. These hydrogels can improve clinical outcomes in the treatment of infected wounds.

Guar gum and gelatin-based hydrogel wound dressing loaded calcium-containing nanoparticles: Simpler preparation, faster hemostasis and faster pro-wound healing properties

In this work, we prepared a novel calcium-containing nanoparticles (CaNPs) and added it to a hydrogel composed of guar gum (GG) and gelatin (Gel) as a backbone to prepare a novel hydrogel (GG@Gel-Ca) with rapid hemostasis, antibacterial effect and wound healing promotion. We conducted a series of test to characterize the structure and properties of CaNPs and GG@Gel-Ca hydrogel. The results showed that CaNPs had been successfully prepared and had regular morphology, and the GG@Gel-Ca hydrogel had good swelling ability, good antibacterial ability and excellent hemocompatibility/hemostasis and perfect cytocompatibility. Animal experiments also showed that GG@Gel-Ca hydrogel was able to achieve rapid hemostasis in the rat liver hemostasis model and it could also accelerate wound healing in S. aureus infections. In summary, we developed an innovative and practical method to prepare a gentle hydrogel, employing two natural polysaccharides that remained unmodified and untreated with chemicals. By incorporating the prepared calcium nanoparticles into this hydrogel, we successfully achieved effective hemostasis. Therefore, the GG@Gel-Ca hydrogel has the potential for application as hemostatic wound dressings with antibacterial properties and good wound healing.

Polyphenols in wound healing: unlocking prospects with clinical applications.

Wound healing is a multifaceted, complex process that factors like aging, metabolic diseases, and infections may influence. The potentiality of polyphenols, natural compounds, has shown anti-inflammatory and antimicrobial properties in promoting wound healing and their potential applications in wound management. The studies reviewed indicate that polyphenols have multiple mechanisms that promote wound healing. This involves enhancing antioxidant defenses, reducing oxidative stress, modulating inflammatory responses, improving healing times, reducing infection rates, and enhancing tissue regeneration in clinical trials and in vivo and in vitro studies. Polyphenols have been proven to be effective in managing hard-to-heal wounds, especially in diabetic and elderly populations. Polyphenols have shown significant benefits in promoting angiogenesis and stimulating collagen synthesis. Polyphenol treatment has been demonstrated to have therapeutic effects in wound healing and chronic wound management. Their ability to regulate key healing processes makes them suitable for new wound care products and treatments. Future research should enhance formulations and delivery methods to optimize polyphenols' bioavailability and therapeutic efficacy in wound management approaches.

Micro-fluidic covalent immobilization of multi-gradient RGD peptides on a gelatin surface for studying endothelial cell migration.

Collective endothelial migration is a hallmark of wound healing, which is regulated by spatial concentration gradients of extracellular biochemical factors. Arginine-glycine-aspartate (RGD) peptides play a vital role in regulating cell migration through specific binding to integrins. In this study, a micro-fluidic technology combined with a photopolymerization technique is developed to create gelatin methacryloyl (GelMA)-based substrates with various concentration gradients of RGD peptides. The capability of generating linear and nonlinear RGD concentration gradients was quantitatively verified through numerical simulation and immunohistochemical quantitative experiments. The results of the concentration gradients show a strong concurrence between the immunohistochemical quantification experiments and numerical simulations. Furthermore, endothelial migration experiments were conducted with various concentration gradients of RGD peptides. We have observed that endothelial cells on the surface of gels with a linear concentration gradient exhibit a larger cell area, a longer cell perimeter, and more stress fiber density. Furthermore, the cells demonstrate directional alignment and migration towards regions with a higher RGD concentration. High concentration gradients significantly enhance endothelial cell migration, consistent with observations on surfaces of gels with nonlinear concentration gradients. In brief, we proposed a simple and effective micro-fluidic photopolymerization technique capable of generating diverse concentration gradients of RGD and probing their effects on cell migration. The results suggest that regulating the RGD peptide concentration gradients can alter the migration of endothelial cells, showing potential for promoting wound healing.

Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting

The transcription factor NRF2 plays an important role in many biological processes and is a promising therapeutic target for many disease states. NRF2 is highly expressed in the skin and is known to play a critical role in diabetic wound healing, a serious disease process for which treatment options are limited. However, many existing NRF2 activators display off-target effects due to their electrophilic mechanism, underscoring the need for alternative approaches. In this work, we investigated two recently described non-electrophilic NRF2 activators, ADJ-310 and PRL-295, and demonstrated their efficacy in vitro and in vivo in human keratinocytes and Leprdb/db diabetic mice. We also compared the downstream targets of PRL-295 to those of the widely used electrophilic NRF2 activator CDDO-Me by RNA sequencing. Both ADJ-310 and PRL-295 maintained human keratinocyte cell viability at increasing concentrations and maintained or improved cell proliferation over time. Both compounds also increased cell migration, improving in vitro wound closure. ADJ-310 and PRL-295 enhanced the oxidative stress response in vitro, and RNA-sequencing data showed that PRL-295 activated NRF2 with a narrower transcriptomic effect than CDDO-Me. In vivo, both ADJ-310 and PRL-295 improved wound healing in Leprdb/db diabetic mice and upregulated known downstream NRF2 target genes in treated tissue. These results highlight the non-electrophilic compounds ADJ-310 and PRL-295 as effective, innovative tools for investigating the function of NRF2. These compounds directly address the need for alternative NRF2 activators and offer a new approach to studying the role of NRF2 in human disease and its potential as a therapeutic across multiple disease states.

A Review of Antimicrobial Peptides: Structure, Mechanism of Action, and Molecular Optimization Strategies

Antimicrobial peptides (AMPs) are bioactive macromolecules that exhibit antibacterial, antiviral, and immunomodulatory functions. They come from a wide range of sources and are found in all forms of life, from bacteria to plants, vertebrates, and invertebrates, and play an important role in controlling the spread of pathogens, promoting wound healing and treating tumors. Consequently, AMPs have emerged as promising alternatives to next-generation antibiotics. With advancements in systems biology and synthetic biology technologies, it has become possible to synthesize AMPs artificially. We can better understand their functional activities for further modification and development by investigating the mechanism of action underlying their antimicrobial properties. This review focuses on the structural aspects of AMPs while highlighting their significance for biological activity. Furthermore, it elucidates the membrane targeting mechanism and intracellular targets of these peptides while summarizing molecular modification approaches aimed at enhancing their antibacterial efficacy. Finally, this article outlines future challenges in the functional development of AMPs along with proposed strategies to overcome them.

A Programmable Handheld Extrusion-Based Bioprinting Platform for In Situ Skin Wounds Dressing: Balance Mobility and Customizability.

Bioprinting technology plays a crucial role for constructing tissue substitutes. However, the mismatched scaffold shapes and the poor treatment timeliness limit its clinical translational application. In situ printing technology that prints bioregenerants directly inside patient's body can meet the needs of specific tissue repair. This study develops a smartphone controlled handheld bioprinter for in situ skin wounds dressing. The mini bioprinter can be handheld and placed on any printing surface to create strips, complex patterns, and 3D structures, and can be equipped with microchannel needles to expand functionality. The size of the strips as well as the printing path can be programmed and controlled by the smartphone to ensure the precision of the printed product quality. Furthermore, the device not only allows for smooth switching between different bioinks for printing heterogeneous structure, but also allows for fast and uniform coverage of large wound surfaces. When dealing with complex wounds in vitro & vivo, the printer can effectively fill and precisely close wounds, promoting wound healing. The programmable handheld bioprinter can balance mobility and customizability in the management of skin wounds and is expected to realize its potential for emergency medical treatment in condition-constrained scenarios, such as battlefields or disaster areas.

Bimetallic FeCo metal–organic framework based cascade reaction system: Enhanced peroxidase activity for antibacterial performance

Metal-organic frameworks (MOFs), as a peroxidase (POD), can catalyze the conversion of H2O2 to reactive oxygen species (ROS) for antibacterial application. To achieve strong antibacterial activity, it is necessary to improve the enzyme-like activity of MOFs. In this study, FexCoMOF was synthesized by incorporating Co(II) to improve the electron transfer of Fe(III)/Fe(II), which enhanced its redox capacity as a nanozyme and further promoted the generation of hydroxyl radical (⋅OH), exhibiting higher POD activity. Doping with different amounts of Co(II) altered the particle size, specific surface area, and surface defects of FexCoMOF, thus exhibiting differential enzyme-like activities. Additionally, a glucose-responsive enzyme cascade reaction system based on Fe4CoMOF/glucose oxidase (GOx) was established. In the presence of glucose, the in situ-generated substrate H2O2 was in contact with the catalytic site and the generated gluconic acid enabled Fe4CoMOF to maintain maximum enzyme activity under physiological pH conditions, avoiding damage caused by the use of exogenous high concentrations of H2O2. In the in vitro antibacterial experiment, the minimum inhibitory concentration (MIC) of Fe4CoMOF/GOx was 10 μg mL−1 for Escherichia coli (E. coli) and 5 μg mL−1 for Staphylococcus aureus (S. aureus) (∼108 CFU mL−1). The increase in enzyme activity resulted in a considerable reduction in the dose of the antibacterial agent, which was conducive to improving bio-safety. The in vivo experiment in mice demonstrated that the glucose-responsive Fe4CoMOF-based cascade reaction system had excellent antibacterial properties and remarkably promoted wound healing. The antibacterial agent based on bimetallic MOF developed in this work provides a new idea for cascade catalytic antibacterial therapy and will have remarkable application prospects in biomaterials and nanomedicine.

Construction and Performance Study of an Injectable Dual-Network Hydrogel Dressing with Inherent Drainage Function.

With the widespread utilization of moist wound dressings, the extended healing time and increased risk of wound infection caused by excessively moist environments have garnered significant attention. The development of hydrogel dressings that can effectively control the wound moisture level and promote healing is very important. Inspired by the pore-opening perspiration effect of the skin, this study constructed an injectable dual-network hydrogel, CMCS-OSA/AG/MXene, by the composition of a dynamic covalent network of carboxymethyl chitosan and oxidized sodium alginate based on the Schiff base and hydrogen bond network of the thermosensitive low-melting-point agar with the advantage of the upper critical solution temperature (UCST) effect. Under near-infrared (NIR) light stimulation, the CMCS-OSA/AG/MXene hydrogel shows characteristics conducive to rapid removal of wound exudate while maintaining an appropriate moist environment for the wound and excellent antibacterial effects with its photothermal responses. The excellent conductivity of the hydrogel can also promote cell proliferation under external electrical stimulation (ES). Further validation through animal experiments on a full-thickness skin defect model demonstrates the excellent capability of CMCS-OSA/AG/MXene in accelerating wound healing. This work provides an innovative approach to the development of injectable hydrogel dressing materials with inherent drainage functionality and shows a new avenue to wound moisture control and wound healing promotion.

Radical-Scavenging Violet Phosphorus Nanosheets for Attenuating Hyperinflammation and Promoting Infected Wound Healing.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7nm VPNSs arefabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications.

Lactobacillus rhamnosus GG-derived extracellular vesicles promote wound healing via miR-21-5p-mediated re-epithelization and angiogenesis

Extracellular vesicles (EVs), especially those derived from stem cells, have emerged as a novel treatment for promoting wound healing in regenerative medicine. However, the clinical application of mammalian cells-derived EVs is hindered by their high cost and low yields. Inspired by the ability of EVs to mediate interkingdom communication, we explored the therapeutic potential of EVs released by the probiotic strain Lactobacillus rhamnosus GG (LGG) in skin wound healing and elucidated the underlying mechanism involved. Using full-thickness skin wound-healing mouse models, we found that LGG-EVs accelerated wound healing procedures, including increased re-epithelialization and promoted angiogenesis. Using in vitro experiments, we further demonstrated that LGG-EVs boosted the proliferation and migration capacities of both epithelial and endothelial cells, as well as promoted endothelial tube formation. miRNA profiling analysis revealed that miR-21-5p was highly enriched in LGG-EVs and LGG-EV treatment significantly increased miR-21-5p level in recipient cells. Mechanically, LGG-EVs induced regulatory effects via miR-21-5p mediated metabolic signaling rewiring. Our results suggest that EVs derived from LGG could serve as a promising candidate for accelerating wound healing and possibly for treating chronic and impaired healing conditions.Graphical abstract

Development of a Multilayer Film Including the Soluble Eggshell Membrane Fraction for the Treatment of Oral Mucosa Lesions

Background/Objectives: Oral diseases causing mucosal lesions are normally treated with local or systemic anti-inflammatory, analgesic and antimicrobial agents. The development of topical formulations, including wound-healing promoters, might speed up the recovery process, improving patients’ quality of life, and reduce the risk of deterioration in health conditions. In this study, a mucoadhesive multilayer film, including a novel biocompatible substance (solubilized eggshell membrane, SESM), was rationally designed. Methods: The SESM preparation procedure was optimized and its biological effects on cell proliferation and inflammation marker gene expression were evaluated in vitro; preformulation studies were conducted to identify the most promising polymers with film-forming properties; then, trilayer films, consisting of an outer layer including chlorhexidine digluconate as a model drug, a supporting layer and a mucoadhesive layer, incorporating SESM, were prepared using the casting method and their mechanical, adhesion and drug release control properties were evaluated. Results: SESM proved to possess a notable wound-healing capacity, inducing a wound closure of 84% in 24 h without inhibiting blood clotting. The films revealed a maximum detachment force from porcine mucosa of approx. 1.7 kPa and maximum in vivo residence time of approx. 200–240 min; finally, they released up to 98% of the loaded drug within 4 h. Conclusions: The formulated trilayer films were found to possess adequate properties, making them potentially suitable for protecting oral lesions and favoring their rapid healing, while releasing antimicrobial substances that might be beneficial in reducing the risk of bacterial infections.

Ionically assembled hemostatic powders with rapid self-gelation, strong acid resistance, and on-demand removability for upper gastrointestinal bleeding.

Upper gastrointestinal bleeding (UGIB) is bleeding in the upper part of the gastrointestinal tract with an acidic and dynamic environment that limits the application of conventional hemostatic materials. This study focuses on the development of N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride/phytic acid (HTCC/PA, HP) powders with fast hemostatic capability and strong acid resistance, for potential applications in managing UGIB. Upon contact with liquids within 5 seconds, HP powders rapidly transform into hydrogels, forming ionic networks through electrostatic interactions. The ionic crosslinking process facilitates the HP powders with high blood absorption (3.4 times of self-weight), sufficient tissue adhesion (5.2 and 6.1 kPa on porcine skin and stomach, respectively), and hemostasis (within 15 seconds for in vitro clotting). Interestingly, the PA imparts the HP powders with strong acid resistance (69.8% mass remaining after 10 days of incubation at pH 1) and on-demand removable sealing while HTCC contributes to fast hemostasis and good wet adhesion. Moreover, the HP powders show good biocompatibility and promote wound healing. Therefore, these characteristics highlight the promising clinical potential of HP powders for effectively managing UGIB.

Mangiferin Represses Inflammation in Macrophages Under a Hyperglycemic Environment Through Nrf2 Signaling.

Inflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Mangiferin, a known Nrf2 activator, was evaluated for its ability to counteract the hyperglycemia-induced inhibition of Nrf2 and enhance antioxidant defenses. The protective effects of mangiferin on macrophages in a hyperglycemic environment were assessed by examining the expression of Nrf2, NF-κB, NLRP3, HO-1, CAT, COX-2, IL-6, and IL-10 through gene and protein expression analyses using qPCR and immunoblotting, respectively. The mangiferin-mediated nuclear translocation of Nrf2 was evidenced, leading to a robust antioxidant response in macrophages exposed to a hyperglycemic microenvironment. This activation suppressed NF-κB signaling, reducing the expression of pro-inflammatory mediators such as COX-2 and IL-6. Additionally, mangiferin decreased NLRP3 inflammasome activation and reactive oxygen species accumulation in hyperglycemia exposed macrophages. Our findings revealed that mangiferin alleviated hyperglycemia-induced reductions in AKT phosphorylation, highlighting its potential role in modulating key signaling pathways. Furthermore, mangiferin significantly enhanced the invasiveness and migration of macrophages in a hyperglycemic environment, indicating its potential to improve wound healing. In conclusion, this study suggests that mangiferin may offer a promising therapeutic approach for managing inflammation and promoting wound healing in diabetic patients by regulating Nrf2 activity in hyperglycemia-induced macrophages.