Recovery Of Wounds Research Articles

Fe-based Nanozyme with photothermal activity prepared from polymerization-induced self-assembly assays boosts the recovery of bacteria-infected wounds

Fe-based Nanozyme with photothermal activity prepared from polymerization-induced self-assembly assays boosts the recovery of bacteria-infected wounds

A straightforward strategy to modulate ROS generation of AIE photosensitizers for type-I PDT

Type-I photodynamic therapy (PDT), valued for its reduced oxygen requirement, generates highly cytotoxic •OH radicals. However, conventional strategies for developing type-I photosensitizers (PSs) are complex and involve intricate organic synthesis. Herein, we present a novel strategy to alter the generation of reactive oxygen species (ROS) by simply manipulating the twisting degree of donor–acceptor (D−A) type aggregation-induced emission (AIE) PSs. Specifically, natural saturated fatty acids are employed to modulate the twisting state of AIE PSs, with higher doping ratios yielding more twisted structures and increased type-I ROS generation. In contrast, fatty acids with higher crystallinity promote planar structures and type-II ROS generation. Theoretical calculations suggest that AIE PSs with highly twisted structures lead to a prominent reduction in ΔEST and effective separation of electron−hole pairs, thereby favoring efficient intersystem crossing and charge transfer. The PDT system primarily driven by type-I ROS exhibits efficient bactericidal activity against clinically drug-resistant bacteria, which remarkably accelerates the recovery of bacteria-infected wounds in mice. This study demonstrates the first example of modulating ROS generation type by manipulating the twisting degree of D−A type AIE PSs, eliminating the need for intricate molecular design and organic synthesis. The proposed strategy opens up new avenues for advancing PDT applications.

Advanced Palladium Nanosheet-Enhanced Phototherapy for Treating Wound Infection Caused by Multidrug-Resistant Bacteria.

With the increasing spread of multidrug-resistant (MDR) bacteria worldwide, it is needed to develop antibiotics-alternative strategies for the treatment of bacterial infections. This work develops a multifunctional single-component palladium nanosheet (PdNS) with broad-spectrum and highly effective bactericidal activity against MDR bacteria. PdNS exerts its endogenous nanoknife (mechanical cutting) effect and peroxidase-like activity independent of light. Under near-infrared region (NIR) light irradiation, PdNS exhibits photothermal effect to produce local heat and meanwhile possesses photodynamic effect to generate 1O2; notably, PdNS has catalase-like activity-dependent extra photodynamic effect upon H2O2 addition. PdNS+H2O2+NIR employs a collectively synergistic mechanism of nanoknife effect, peroxidase/catalase-like catalytic activity, photothermal effect, and photodynamic effect for bacterial killing. PdNS+H2O2+NIR causes compensatory elevated phospholipid biosynthesis, disordered energy metabolism, increased cellular ROS levels and excessive oxidative stress, and inhibited nucleic acid synthesis in bacteria. In mice, PdNS+H2O2+NIR gives >92.7% bactericidal rates at infected wounds and almost the full recovery of infected wounds, and it leads to extensive down-regulation of proinflammatory pathways and comprehensive up-regulation of wound healing pathways, conferring elevated inflammation resolution and meanwhile accelerated wound repair. PdNS+H2O2+NIR represents a highly efficient nanoplatform for photoenhanced treatment of superficial infections.

In Vitro Wound-Healing Potential of Phenolic and Polysaccharide Extracts of Aloe vera Gel.

The present study aimed to conduct a comparative investigation of the biological properties of phenolic and polysaccharide extracts obtained using an ultrasound-assisted technique from Aloe vera gel and their effects on each stage of the wound healing process in in vitro experimental models. HPLC analysis showed that the phenolic extract contained aloin, ferulic, and caffeic acid, as well as quercetin dihydrate, as major compounds. Capillary zone electrophoresis indicated the prevalence of mannose and glucose in the polysaccharide extract. Cell culture testing revealed the anti-inflammatory properties of the phenolic extract at a concentration of 0.25 mg/mL through significant inhibition of pro-inflammatory cytokines-up to 28% TNF-α and 11% IL-8 secretion-in inflamed THP-1-derived macrophages, while a pro-inflammatory effect was observed at 0.5 mg/mL. The phenolic extract induced 18% stimulation of L929 fibroblast proliferation at a concentration of 0.5 mg/mL, enhanced the cell migration rate by 20%, and increased collagen type I synthesis by 18%. Moreover, the phenolic extract exhibited superior antioxidant properties by scavenging free DPPH (IC50 of 2.50 mg/mL) and ABTS (16.47 mM TE/g) radicals, and 46% inhibition of intracellular reactive oxygen species (ROS) production was achieved. The polysaccharide extract demonstrated a greater increase in collagen synthesis up to 25%, as well as antibacterial activity against Staphylococcus aureus with a bacteriostatic effect at 25 mg/mL and a bactericidal one at 50 mg/mL. All these findings indicate that the phenolic extract might be more beneficial in formulations intended for the initial phases of wound healing, such as inflammation and proliferation, while the polysaccharide extract could be more suitable for use during the remodeling stage. Moreover, they might be combined with other biomaterials, acting as efficient dressings with anti-inflammatory, antioxidant, and antibacterial properties for rapid recovery of chronic wounds.

Glycyrrhizic acid and glycyrrhetinic acid loaded cyclodextrin MOFs with enhanced antibacterial and anti-inflammatory effects for accelerating diabetic wound healing

A water stable cyclodextrin MOF (Cu-SD) was synthesized with γ-cyclodextrin derivative as organic ligand and Cu2+ as metal center to co-crystallizely load glycyrrhizic acid (GL) and glycyrrhetinic acid (GA). Cu-SD has a high drug loading capacity for GL (499.91 μg/mg) and GA (112.37 μg/mg), and the drug-loaded materials had a controlled release in different meadiums. In addition, Cu-SD and its drug loaded materials demonstrated better inhibiting α-glucosidase activity than the control drug acarbose. Furthermore, Cu-SD presented excellent antibacterial activity, and the antibacterial activity was significantly enhanced after GA and GL being encapsulated by Cu-SD. Moreover, both free and drug-loaded materials had good anti-inflammatory activities, and the anti-inflammatory effects of GL@Cu-SD and GA@Cu-SD were superior to those of their corresponding free drugs. Cu-SD, GL@Cu-SD and GA@Cu-SD demonstrated good biocompatibility and were applied to treat the wounds of diabetic rats. The experimental results showed that GL@Cu-SD and GA@Cu-SD had good promoting effects on the recovery of chronic diabetic wounds by suppressing wound inflammation.

Accelerated, injectable, self-healing, scarless wound dressings using rGO reinforced dextran/chitosan hydrogels incorporated with PDA-loaded asiaticoside

The process of wound healing is intricate and complex, necessitating the intricate coordination of various cell types and bioactive molecules. Despite significant advances, challenges persist in achieving accelerated healing and minimizing scar formation. Herein, a multifunctional hydrogel engineered via dynamic Schiff base crosslinking between oxidized dextran and quaternized chitosan, reinforced with reduced graphene oxide (rGO) is reported. The resulting OQG hydrogels demonstrated injectability to aid in conforming to irregular wound geometries, rapid self-healing to maintain structural integrity and adhesion for intimate integration with wound beds. Moreover, the developed hydrogels possessed antioxidant and antibacterial activities, mitigating inflammation and preventing infection. The incorporation of conductive rGO further facilitated the transmission of endogenous electrical signals, stimulating cell migration and tissue regeneration. In addition, the polydopamine-encapsulated asiaticoside (AC@PDA) nanoparticles were encapsulated in OQG hydrogels to reduce scar formation during in vivo evaluations. In vitro results confirmed the histocompatibility of the hydrogels to promote cell migration. The recovery of the full-thickness rat wounds revealed that these designed OQG hydrogels with the incorporation of AC@PDA nanoparticles could accelerate wound healing, reduce inflammation, facilitate angiogenesis, and minimize scarring when implemented. This multifunctional hydrogel system offers a promising strategy for enhanced wound management and scarless tissue regeneration, addressing the multifaceted challenges in wound care.

Kirigami-inspired artificial spidroin microneedles for wound patches

Intelligent wound management has important potential for promoting the recovery of chronic wounds caused by diabetes. Here, inspired by the field of kirigami, smart patterned high-stretch microneedle dressings (KPMDs) based on gene-modified spider silk proteins were developed to achieve sensitive biochemical and physiological sensing. The spider silk protein (spidroin) has excellent tensile properties, ductility, toughness and biocompatibility. Notably, the kirigami method-prepared kirigami structure of the spidroin MN dressing had a high tensile strength , while its ductility reached approximately 800 %. Moreover, the unique optical properties of photonic crystals allow for fluorescence enhancement, providing KPMD with color-sensitive properties suitable for wound management and clinical guidance. Furthermore, to improve the sensitivity of KPMD-s to motion monitoring, a microelectronic matrix was integrated on its surface. These distinct material properties suggest that this research lays the foundation for a new generation of high-performance biomimetic diatomaceous earth materials for application.

Formulation and Evaluation of Topical Delivery Diosgenin Emulgel for Diabetic Wounds

A variety of cellular processes work together in a highly coordinated manner to facilitate a complex and dynamic process of wound healing ensuring the efficient restoration of injured tissue. Diosgenin, a plant sterol saponin is primarily found in various plants. The aim of this research was to create an emulgel containing Diosgenin and examine its effects on wound healing in diabetic rats with excision wounds. Histopathological findings further supported the efficacy of the emulgel and results indicate that the application of Diosgenin Emulgel (DE) shows an effective approach for healing of diabetic wounds. The objective of the research stands to explore the possibility of formulation development and wound-healing capabilities of DE. The study evaluated the wound healing effects of the DE in Streptozotocin-induced (STZ) (55 mg/kg) given by intraperitoneal route diabetes and control group. The emulgel was topically applied to assess its effectiveness in promoting wound healing. The application of DE on the rat wounds resulted in a notable wound closure within a 21-day period and significant epithelization was observed with p < 0.001. The study concluded that the formulation demonstrated remarkable effectiveness in promoting the functional recovery of diabetic wounds.

Treatment of Acute Wound Infections by Degradable Polymer Nanoparticle with a Synergistic Photothermal and Chemodynamic Strategy.

Mild-heat photothermal antibacterial therapy avoids heat-induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo-conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co-assemble with DSPE-mPEG2000 into nanoparticle NPM123/Fc. NPM123/Fc under 1064nm laser irradiation (NPM123/Fc+NIR-II) generates mild heat and additionally more toxic ∙OH from endogenous H2O2, displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc+NIR-II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc+NIR-II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc+NIR-II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc+NIR-II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics-alternative anti-infective measure.

Highly Elastic, Bioresorbable Polymeric Materials for Stretchable, Transient Electronic Systems

HighlightsThe paper introduces a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), with remarkable mechanical properties, including high elongation-at-break (< 1300%), resilience, and toughness (75 MJ m−3) for soft and transient electronics.Fabrication of conducting polymers with PGCL yields stretchable, conductive composites for transient electronic devices, functioning reliably under external strains.The study demonstrates the feasibility of a disintegrable electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds on soft, time-dynamic tissues or versatile biomedical areas of interest.

Accelerated wound healing after topical application of hyaluronic acid cotton to hemorrhoidectomy wounds in a rat model.

Anal wounds following hemorrhoidectomy can lead to severe pain and postoperative bleeding, impacting patient recovery and quality of life. Hyaluronic acid (HA) stimulates tissue regeneration and wound healing by accelerating cell migration and proliferation. This study aimed to investigate the differences in wound healing rate and completeness of recovery of perianal wounds topically treated with HA-soaked cotton in a murine model. Forty-eight 8-week-old Sprague-Dawley rats with perianal wounds created using a biopsy punch were divided into 2 groups: simple dressing with gauze (control) and topical HA-soaked cotton. A single application of HA-soaked cotton was administered after surgery. Wound healing rate and completeness of recovery were evaluated by measuring the healed area and conducting histological analyses. The HA-cotton group exhibited a shorter complete wound healing duration compared to the control group (13.9 days vs. 16.4 days, P = 0.031). Differences in wound healing area between the 2 groups were greatest on postoperative day 2 (51.6% vs. 28.8%, P < 0.001). The HA-cotton group exhibited fewer cases of granulation tissue (2 vs. 5) or redness (0 vs. 3) upon complete wound healing. Histologically, the HA-cotton group showed accelerated reepithelialization, rapid shift to lymphocyte-dominant inflammation, enhanced fibroblast proliferation, and increased collagen deposition compared to the control group. Herein, topical application of HA-soaked cotton on perianal wounds in rats resulted in accelerated wound healing, particularly in the initial stages, and improved completeness of recovery, underscoring the potential of the topical application of HA-soaked cotton on hemorrhoidectomy wounds in human patients to improve wound healing.

Asymmetric porous hydrogel encapsulating vulcanized molecular brushes with anti-bacterial adhesion, anti-infection, and pro-healing properties towards infected wound treatment.

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.

Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy.

Adipose mesenchymal stem cell-derived exosomes (ADSC-Exos) have great potential in the field of tissue repair and regenerative medicine, particularly in cases of refractory diabetic wounds. Interestingly, autophagy plays a role in wound healing, and recent research has demonstrated that exosomes are closely associated with intracellular autophagy in biogenesis and molecular signaling mechanisms. Therefore, this study aimed to investigate whether ADSC-Exos promote the repair of diabetic wounds by regulating autophagy to provide a new method and theoretical basis for the treatment of diabetic wounds. Western blot analysis and autophagy double-labelled adenovirus were used to monitor changes in autophagy flow in human immortalized keratinocyte cell line (HaCaT) cells. ADSC-Exos were generated from ADSC supernatants via ultracentrifugation. The effectiveness of ADSC-Exos on HaCaT cells was assessed using a live-cell imaging system, cell counting kit-8 and cell scratch assays. The cells were treated with the autophagy inhibitor bafilomycin A1 to evaluate the effects of autophagy on cell function. The recovery of diabetic wounds after ADSC-Exo treatment was determined by calculating the healing rates and performing histological analysis. High-throughput transcriptome sequencing was used to analyze changes in mRNA expression after the treatment of HaCaT cells with ADSC-Exos. ADSC-Exos activated autophagy in HaCaT cells, which was inhibited by high glucose levels, and potentiated their cellular functions. Moreover, ADSC-Exos in combination with the autophagy inhibitor bafilomycin A1 showed that autophagy defects further impaired the biological function of epidermal cells under high-glucose conditions and partially weakened the healing effect of ADSC-Exos. Using a diabetes wound model, we found that ADSC-Exos promoted skin wound healing in diabetic mice, as evidenced by increased epidermal autophagy and rapid re-epithelialization. Finally, sequencing results showed that increased expression of autophagy-related genes nicotinamide phosphoribosyltransferase (NAMPT), CD46, vesicle-associated membrane protein 7 (VAMP7), VAMP3 and eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) may contribute to the underlying mechanism of ADSC-Exo action. This study elucidated the molecular mechanism through which ADCS-Exos regulate autophagy in skin epithelial cells, thereby providing a new theoretical basis for the treatment and repair of skin epithelial damage by ADSC-Exos.

Effects of dose-dependent chronic caffeine consumption in a rat burn wound model: Histopathological and immunohistochemical evaluation.

Using histopathological and immunohistochemical methods, we aimed to examine the dose-dependent effects of chronic caffeine consumption on the recovery of burn wounds in an in vivo rat model. Forty-five rats were randomly assigned to a high-dose group (20 mg/kg per day for eight weeks; n=15), a low-dose group (10 mg/kg per day for eight weeks; n=15), or a control group (n=15). The burn model was created in rats. The groups were separated into three subgroups (n=5) based on the day after injury (7th, 14th, or 21st day). The wound area, wound closure percentage, and histopathological and immunohistochemical reactivity were evaluated. Successful wound healing was noted in rats treated with low doses of caffeine, similar to the control group. Pathology revealed low re-epithelization, low inflammation, and high granulation in the high-dose group. In addition, there was a significant difference between the control and high-dose groups regarding the immunohistochemical reactivity of αVβ3 integrin, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) (P<0.05). We demonstrated that chronic caffeine consumption in rats adversely affects the recovery process of wounds in a dose-dependent manner. This effect may occur through delayed wound healing via the molecules MMP-9, αVβ3 integrin, and VEGF. Treatment that modulates these molecules can lead to enhanced and quicker recovery of damaged skin in coffee lovers.

Transparent silk fibroin film-facilitated infected-wound healing through antibacterial, improved fibroblast adhesion and immune modulation.

The clinical application of regenerated silk fibroin (RSF) films for wound treatment is restricted by its undesirable mechanical properties and lack of antibacterial activity. Herein, different pluronic polymers were introduced to optimize their mechanical properties and the RSF film with 2.5% pluronic F127 (RSFPF127) stood out to address the above issues owing to its satisfactory mechanical properties, hydrophilicity, and transmittance. Diverse antibacterial agents (curcumin, Ag nanoparticles, and antimicrobial peptide KR-12) were separately encapsulated in RSFPF127 to endow it with antibacterial activity. In vitro experiments revealed that the medicated RSFPF127 could persistently release drugs and had desirable bioactivities toward killing bacteria, promoting fibroblast adhesion, and modulating macrophage polarization. In vivo experiments revealed that medicated RSFPF127 not only eradicated methicillin-resistant Staphylococcus aureus in the wound area and inhibited inflammatory responses, but also facilitated angiogenesis and re-epithelialization, regardless of the types of antibacterial agents, thus accelerating the recovery of infected wounds. These results demonstrate that RSFPF127 is an ideal matrix platform to load different types of drugs for application as wound dressings.

Hollow porous PLA/PBAT composite microfibers with enhanced toughness and prolonged drug release for wound healing

An appropriate wound dressing is necessary to enhance the recovery of wounds and the restoration of tissue after the skin gets injured. In this study, a hollow porous microfiber (HPMF) scaffold composed of a combination of polylactic acid (PLA)/polybutylene adipate/butylene terephthalate (PBAT)/polyvinyl alcohol (PVA) was developed using coaxial electrospinning for wound healing. The porous structure of PLA/PBAT HPMFs was formed by dissolving PVA in water. The results showed that when maintaining a PLA: PBAT weight ratio of 7:3, high-quality porous PLA/PBAT composites were achieved, leading to a 36.25% increase in toughness and a 4.9% increase in biodegradability compared to pure PLA. Furthermore, in vivo wound healing assays suggest that composites successfully loaded can effectively promote wound healing on the 13th day. Therefore, this work underscores the significant potential of PLA/PBAT HPMF dressing for wound repair.

Клінічне дослідження ефективності гідрогелевих пов’язок із лідокаїном у зменшенні запалення епізіотомної рани, післяпологового стресу та болю

Episiotomy, like other surgical interventions, triggers inflammatory responses within the physiological context by engaging proinflammatory mediators such as interleukins, cytokines, and prostaglandins. The painful experiences associated with episiotomy have the potential to significantly impact both the physical and emotional well-being of the parturient, particularly when considering individual variables such as the extent of the incision and the presence of complicating factors. In the postpartum period, the presence of fear, anxiety, and anticipation of pain may contribute to heightened stress levels, thereby exerting a profound impact on the emotional state of the parturient. Emotional stress, in turn, has the capacity to modulate pain perception, amplifying the discomfort associated with the incision. Elevated concentrations of stress hormones can influence immune responsiveness and inflammatory cascades, subsequently affecting the intricate process of episiotomy healing. Purpose - to examine determinants influencing the recovery of episiotomy wounds, encompassing inflammation markers, postpartum pain, and psychosocial stress. Materials and methods. A prospective randomized study analyzed clinical, laboratory, and historical data from 123 primiparous patients with episiotomy wounds at Kyiv City Maternity Hospital No. 5 during 2021-2022. The study comprised a comparison group (63 patients receiving standard treatment) and a research group (60 patients additionally utilizing hydrogel dressings with lidocaine). Both groups underwent assessment for heat shock protein Hsp60 and bacterial homolog GroEl levels, serum interleukin-6 dynamics, cortisol levels, pain, and stress levels according to the Edinburgh Postnatal Depression Scale. Statistical analysis employed the Mann-Whitney U test and EZR v. 1.54 statistical package. Results. No statistically significant differences were found in Hsp60 and GroEl levels, interleukin-6, cortisol, and pain levels after 24 hours between the comparison and research groups (p&gt;0.05). However, interleukin-6 levels after 72 hours postpartum were 12.35 pg/ml (10.478-14.09) vs. 6.9 pg/ml (4.50-9.85); p&lt;0.001; cortisol levels - 25.22 μg/dl (23.113-29.335) vs. 23.5 μg/dl (19.6-26.0), respectively; p&lt;0.001. Pain levels by the visual analog scale after 72 hours postpartum were 4 (3-5) points vs. 3 (3-4) points; p&lt;0.001; and at 10 days postpartum - 3 (2-3) points vs. 2 (2-3) points; p=0.010. Stress levels after 72 hours postpartum were 16 (13-19.75) points vs. 11.5 (9-15.5) points; p&lt;0.001. Conclusions. Grasping the intricate interplay of episiotomy, inflammation markers, stress, and pain is pivotal for delivering comprehensive postpartum care. The implementation of evidence-based strategies, such as personalized pain management protocols, psychological support, and systematic monitoring of inflammation markers, can significantly enhance women's well-being and render the postpartum recovery process more comfortable. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Nano-Emulsified Perfluorooctyl Bromide Can Infiltrate Gram-Negative Bacteria and Sensitize Them to Ultrasound.

Gram-negative (G-) bacterial infections remain one of the most urgent global health threats, because the distinctive envelope structure hinders the penetration of therapeutics. Here, we showed that a perfluorooctyl bromide nanoemulsion (PFOB NE) uniquely interacts with G- bacteria. After cell envelope attachment, the PFOB can infiltrate the cell and was diffused throughout. In this process, it impaired the membranes by disintegrating phospholipid molecules, enhancing the consequent ultrasonic cavitation to break the envelope. We identified through ultrasound that the NE had remarkable bactericidal effects against various antibiotic-resistant pathogens. Using in situ sterilization, this approach accelerated the recovery of bacteria-infected murine skin wounds. Thus, combining PFOB and ultrasound might be an alternative tool for conquering the growing threat of G- pathogens.

ApoSEVs-Mediated Modulation of Versatile Target Cells Promotes Diabetic Wound Healing: Unveiling a Promising Strategy.

Diabetic chronic wounds present a formidable challenge in clinical management, lacking effective treatment options. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for tissue repair and regeneration. However, transplanted MSCs often undergo rapid apoptosis, giving rise to heterogeneous extracellular vesicles (EVs), including apoptotic bodies (apoBDs) and apoptotic small extracellular vesicles (apoSEVs). The potential stimulatory role of these EVs in diabetic wound healing remains unknown. In this study, we investigated the effects of apoSEVs derived from adipose-derived mesenchymal/stromal cells (ADSCs) on the recovery of diabetic wounds by modulating the function of versatile target cells. First, we characterized the apoSEVs and apoBDs derived from apoptotic ADSCs. Subsequently, we evaluated the effects of apoSEVs and apoBDs on macrophages, endothelial cells, and fibroblasts, three essential cell types in wound healing, under high-glucose conditions. Furthermore, we developed a gelatin methacryloyl (GelMA) hydrogel for the sustained release of apoSEVs and investigated its therapeutic effects on wound healing in type 2 diabetic mice in vivo. apoSEVs facilitated the polarization of M1 phenotype macrophages to M2 phenotype, promoted proliferation, migration, and tube formation of endothelial cells, and enhanced fibroblast proliferation and migration. However, apoBDs failed to improve the function of endothelial cells and fibroblasts. In vivo, the apoSEVs-loaded GelMA effectively promoted wound healing by facilitating collagen fiber deposition, angiogenesis, and immune regulation. Our study elucidates the beneficial effects of apoSEVs on wound recovery in diabetes and introduces a novel strategy for diabetic wound treatment based on apoSEVs.

Hollow Cobalt Sulfide Nanospheres with Highly Enzyme-like Antibacterial Activities to Accelerate Infected Wound Healing.

The emergence of nanozymes presents a promising alternative to antibiotics for reactive oxygen species-mediated broad-spectrum antimicrobial purposes, but nanozymes still face challenges of low therapeutic efficiency and poor biocompatibility. Herein, we creatively prepared a novel kind of hollow cobalt sulfide (CoS) nanospheres with a unique mesoporous structure that is able to provide numerous active sites for enzyme-like reactions. The results revealed that 50 μg/mL of CoS nanospheres exhibited strong peroxidase- and oxidase-like activities under physiological conditions with the assistance of a low concentration of hydrogen peroxide (H2O2, 100 μM) while possessing highly efficient GSH-depletion ability, which endowed CoS nanospheres with triple enzyme-like properties to combat bacterial infections. The in vitro experiments demonstrated that the CoS nanozyme displayed significant antibacterial effects against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). The in vivo implantation showed that the synthesized CoS effectively eliminated bacteria and promoted the recovery of infected wounds in rats while exhibiting a low cytotoxicity. This study provides a promising treatment strategy to accelerate infected wound healing.