Wound Healing Infection Research Articles

Safety and efficacy of infusional perioperative Tacrolimus therapy in Crohn’s Disease patients undergoing intestinal resection

Introduction: Perioperative optimization of Crohn’s Disease (CD) patients is mandatory in order to ensure favorable outcomes and limit perioperative morbidity such as anastomosis-related complications. The use of perioperative tacrolimus may offer beneficial inflammatory control and improve postoperative outcome. However, it also may exhibit unwanted effects of immunosuppression on infectious complications and wound healing. Methods: This is a single-center, retrospective study of CD patients undergoing intestinal resection between 2009 and 2018. Characteristics of CD patients receiving infusional perioperative Tacrolimus or not were systematically evaluated and exploratively compared. To investigate the impact of Tacrolimus and other predictors on postoperative infectious complications, simple regression with a threshold of p<0.05 was used. Significant predictors of the simple regression analysis, as well as Tacrolimus, were then included into multiple logistic regression. Results: This analysis included 30 patients (34.88%) having received Tacrolimus perioperatively and 56 patients (65.12%) that were not treated with Tacrolimus. In median, 1mg/day of Tacrolimus was given intravenously for 11 days. Adverse events occurred in three patients (10%). The most common adverse events were headache and paresthesia. Tacrolimus showed no significant correlation to postoperative infectious complications. Furthermore, multiple regression analysis found no significant effect of Tacrolimus on postoperative infectious complications when controlling for previously identified confounders. Conclusion: Administration of Tacrolimus showed no negative impact on postoperative infectious complications in the study cohort, indicating safety of perioperative Tacrolimus therapy. By describing in detail our study population of patients receiving perioperative Tacrolimus, we provide data guiding future prospective studies.

Antimicrobial GL13K Peptide-Decorated ZnO Nanoparticles To Treat Bacterial Infections.

As a broad-spectrum antimicrobial material, ZnO nanoparticles (NPs) offer a novel approach to infected wounds in the clinic; however, it is very necessary to improve the antimicrobial performance of ZnO to satisfy the clinic requirements. In this work, a new antimicrobial hybrid ZnO@PDA/GL13K was prepared by attaching the antimicrobial GL13K peptide on the surface of ZnO NPs via polydopamine (PDA) as a covalent bonding agent, which can enhance the reactive oxygen species (ROS) production and damage the cell wall, showing superior antimicrobial efficacy. Besides, the ZnO@PDA/GL13K hybrid can promote the healing of bacterial infected wounds, with the wound area only remaining 1.8% on day 9, about 2 times smaller than that of the ZnO group. Moreover, ZnO@PDA/GL13K also showed good biocompatibility, and no side effect on normal tissue and organs was found, implying that the antimicrobial hybrid may possess prospective application in biomedical fields.

Adhesive, Stretchable, and Photothermal Antibacterial Hydrogel Dressings for Wound Healing of Infected Skin Burn at Joints.

Dressings for infectious skin burn wounds at joints should have therapeutic functions as well as high tissue-adhesion, stretching, and self-healing properties. This makes it difficult for most hydrogel dressings to simultaneously meet the above-mentioned requirements. In this study, poly(vinyl alcohol), anhydrous sodium borax, epigallocatechin gallate, and copper chloride were used to prepare a hydrogel dressing (PBEC) for the infected burn wound healing at joints. The PBEC hydrogel can adhere to a variety of substrates, has a stretching capacity, and quickly self-healing after being damaged. Additionally, the PBEC hydrogel has the properties of reactive oxygen species scavenging, photothermal sterilization, hemostatic ability, and biocompatibility. Finally, the hydrogel could accelerate the process of wound healing in vivo, especially with the assistance of near-infrared radiation. Therefore, the hydrogel dressing shows great potential for clinical application in the healing of infected burn wounds at joints.

Self-powered chitosan/graphene oxide hydrogel band-aids with bioadhesion for promoting infected wounds healing.

Typical anti-infection strategies, such as antibiotics and other antibacterial nanomaterials, are effective in preventing bacterial infections during the wound healing process. Additionally, electrical stimulation (ES) can also inhibit bacterial growth and facilitate skin wound repair. However, self-powered and therapeutic wearable devices combining antibacterial materials with ES are still lacking. In this research, a bio-adhesive band-aid with antibacterial activity and piezoelectric properties made up of a chitosan/graphene oxide (CSGO) hydrogel matrix and a piezoelectric nanogenerator (PENG) patch based on electrospun polyvinylidene difluoride (PVDF) nanofibers is developed for infected wound healing. Specifically, self-adhesive CSGO hydrogels help the band-aid closely adhere to the wound site, and PVDF nanofibers convert biokinetic energy into electricity to provide real-time ES. The in vitro antibacterial test demonstrates that >99 % of S. aureus and E. coli are killed by the treatment of CSGO hydrogel and ES. Remarkably, in the rat model of infected wounds, the assembled band-aid consisting of a PENG of 2.25 cm2 can promote angiogenesis, collagen deposition, and re-epithelialization, greatly accelerating infected wounds healing in 21 days. This study offers a simple and practicable method for the design of wearable bioelectronics, indicating a promising future in personalized healthcare and clinical treatment.

Silk fibroin aerogels with AIE-featured berberine and MXene for rapid hemostasis and efficient wound healing.

Rapid hemostasis and wound healing are crucial in emergency trauma situations for saving patients' lives. Traditional hemostatic materials often have drawbacks such as slow hemostasis and susceptibility to post-hemostasis bacterial infections. Therefore, there is an urgent need for advanced wound dressing materials that can provide both rapid hemostasis and antimicrobial properties. In this study, we designed and fabricated a biocompatible hemostatic silk fibroin (SF) aerogel loaded with aggregation-induced emission (AIE)-featured berberine (BBr) and Ti3C2Tx MXene. The resulting SFMB aerogel demonstrates robust mechanical properties and a porous structure that enables quick hemostasis. This aerogel exhibits photodynamic and photothermal responses for antimicrobial activity, releases BBr upon light exposure to enhance bacterial-killing efficiency (99.33 % in vitro and 99.09 % in vivo), and effectively promotes the healing of infected wounds in vivo through combined photothermal/photodynamic antibacterial and anti-inflammatory mechanisms. Furthermore, the aerogel shows high hemocompatibility and cytocompatibility, supporting its potential biomedical applications. Overall, the synthesized SFMB aerogel holds promise for treating bacteria-infected wounds and for use in first aid applications in clinical settings.

Zinc Oxide-Enhanced Copper Sulfide Nanozymes Promote the Healing of Infected Wounds by Activating Immune and Inflammatory Responses.

Bacterial infection and an excessive inflammatory response are two major factors that affect the healing of infected wounds. The zinc oxide/copper sulfide (ZnO-CuS) microspheres (MSs) developed in this work can kill bacteria and resist inflammation. ZnO-CuS exhibits different enzyme-like activities depending on pH. In acidic environments, ZnO-CuS exhibits peroxidase-like (POD-like) activity and can convert hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) for sterilization. Under neutral conditions, ZnO-CuS removes reactive oxygen species (ROS) and can convert excess ROS into water and oxygen. The in vitro results of the antibacterial test demonstrate the pronounced disruption effect of ZnO-CuS on the bacterial biofilm and cell membrane. The transcriptome sequencing results of wounded animal tissue reveal that ZnO-CuS MSs increase the expression of proteins produced by immune cells, and reduce the expression levels of inflammatory factors at the wound site. Therefore, antimicrobial activity and rapid wound healing can be achieved by regulating the immune response and reducing the inflammatory response. The results from hemolysis, routine blood and blood biochemistry analyses demonstrate the excellent biosecurity of the ZnO-CuS MSs.

Nanoclay Mediated Two-Pronged Strategy for Infected-Wound Healing.

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

A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing

Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago zeylanica L. known for its excellent antibacterial ability. However, the application of PLB is limited because of its poor water solubility, instability, and tendency to sublimate. In this study, we propose a solution by designing a hyaluronic acid (HA)/polyvinylpyrrolidone (PVP) dissolving microneedle patch loaded with PLB/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. PLB was encapsulated into the cavity of HP-β-CD to improve its solubility and stability using the neutralization agitation method. The formation of the inclusion complex significantly increased the water solubility of PLB to 1350 ± 6.8 μg/mL, which is 17 times higher than its original value of 79.3 ± 1.7 μg/mL. The encapsulation efficiency was found to be 94.82 ± 3.34%. In vitro drug release studies, PLB microneedles loaded with PLB/HP-β-CD inclusion complex rapidly released into PBS within 15min. Furthermore, the PLB microneedles exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus) both in vivo and in vitro. They also remarkably accelerated the healing of infected wounds in mice by enhancing collagen deposition and re-epithelialization, reducing inflammation, and stimulating angiogenesis. Overall, this multifunctional microneedle patch shows promising potential for clinical applications in the healing of infected wounds.

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

Nowadays, the overuse of antibiotics has escalated bacterial infections into an increasingly severe global health threat. Developing non-antibiotic treatments has emerged as a promising strategy for treating bacterial infections. Notably, nanozyme-based composite materials have garnered growing interest. Therefore, the efficient preparation of nanozyme is important. Herein, we have presented an efficient method to prepare Fe-based nanozyme through polymerization-induced self-assembly assay to kill bacteria efficiently, which could significantly enhance the healing of infected wounds. Through polymerization-induced self-assembly assay, a large number of uniformly sized micelles, bearing imidazole groups, could be efficiently prepared. These nanoparticles subsequently chelate with Fe ions, followed by pyrolysis and etching processes, resulting in the production of uniformly small-sized nanozymes with high adsorption activity in the near-infrared region. The composite materials could effectively eradicate bacteria via a synergistic strategy of photothermal and catalytic therapies under infected microenvironments. In vivo animal models with full-thickness wounds showed that combination therapy not only eradicates 98 % of the bacteria but also significantly accelerates wound healing. This work underscores the utility of polymerization-induced self-assembly in the preparation of nanozymes and reveals promising applications of nanozymes in wound healing. Statement of significanceThis research introduces a functional nanozyme with photothermal activity, synthesized through polymerization-induced self-assembly, offering a promising non-antibiotic strategy to combat bacterial infections. This strategy enhances wound healing by combining photothermal and catalytic therapies, effectively eradicating drug-resistant bacteria while minimizing damage to healthy tissue. Our findings hold significant implications for the development of advanced antibacterial treatments and offer a robust assay to prepare nanozyme with small sizes. The prepared functional nanoparticles have a potential in wound healing, addressing a critical need in the face of rising antibiotic resistance.

One-step construction of silver nanoparticles immersed hydrogels by triple-helix β-glucans and the application in infectious wound healing

Hydrogels composed of polysaccharides and silver nanoparticles (AgNPs) are widely recognized for their application in wound dressings, particularly for healing wounds prone to infection. Traditional methods for preparing AgNP-immersed hydrogels are often complex, costly, and may lead to sustained cytotoxicity. To address these challenges, we developed a biocompatible, one-step green reduction strategy to generate AgNPs within hydrogels using a triple-helix β-glucan (PCPA) derived from Poria cocos, a renowned Chinese traditional herb. PCPA serves as a reducing agent, converting silver ions into AgNPs while its triple-helix conformation prevents AgNP aggregation. The resulting hydrogel (PAg-G) is injectable and contains uniformly distributed AgNPs. PAg-G exhibits broad-spectrum antimicrobial activity and enhanced bioactivity. The in vivo studies on S.aureus-infected SD rats demonstrated that PAg-G accelerates wound healing within 12 days by down-regulating inflammatory factors such as IL-6 and TNF-α, and up-regulating VEGF and CD31 expression, promoting neovascularization in wound tissues. This innovative one-step construction of AgNP-immersed hydrogels offers a promising approach for the development of antimicrobial hydrogels, especially for treating bacterial-infected wounds.

Quercetin@β-Cyclodextrin Conjugated Keratin/Polyurethane Biocomposite Mats for Infected Diabetic Wound Healing.

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

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.

Electricallymodified bacterial cellulose tailored with plant based green materials for infected wound healing applications

Effective treatment of infected wounds remains a challenge due to the rise of antibiotic-resistant microorganisms. The development of advanced materials with strong antimicrobial properties is necessary to address this issue. In this study, a unique composite of electrically modified bacterial cellulose (EBC) with allantoin (ABC) and zein was developed by dipping diffusion method. Morphological structural analysis revealed a uniform distribution of zein and aligned fibers, confirming the synthesis of the ABC-Zein composite. The formation of ABC-Zein was further confirmed by attenuated total reflection-Fourier transform infrared (ATR-FTIR), which displayed additional peaks corresponding to EBC, indicating the incorporation of zein into ABC. X-ray diffraction (XRD) analysis of ABC-Zein demonstrated a similar crystalline structure with EBC. The ABC-Zein showed mechanical integrity (tensile strength: 1.15 ± 0.21 MPa), thermal stability (degradation temperature: 290 °C), porous structure (porosity: 40.23 ± 0.21 %), and hydrophilic (water contact angle: 53.3 ± 5.3°) properties. Furthermore, the antimicrobial agent terpinen-4-ol (T4O), derived from tea tree oil, was incorporated into the ABC-Zein composite. Biological studies confirmed the antimicrobial efficacy (Staphylococcus aureus inhibition: 88.5 ± 7.19 %) and biocompatible (cell viability: 84.95 ± 5.6 %, hemolysis: 4.479 ± 0.39 %) nature of the T4O-ABC-Zein composite. The combined effects of the aligned fiber structure, zein protein, and antimicrobial T4O significantly enhanced infected wound healing by day 7, promoting inflammatory response, granular tissue formation, cell proliferation, and angiogenesis. By day 14, T4O-ABC-Zein facilitated complete wound healing, with reepithelization, collagen I deposition, and downregulation of CD 31, Ki67, and α-SMA. Overall, the innovative T4O-ABC-Zein composite, with an aligned fiber structure, improved biocompatibility, and antimicrobial properties, holds significant potential for the treatment of infected wounds.

Biomimetic Nanozyme-Decorated Smart Hydrogel for Promoting Chronic Refractory Wound Healing.

Chronic refractory wounds have become a serious threat to human health and are characterized by prolonged inflammation, recurrent bacterial infections, and elevated ROS levels. However, current therapeutic strategies usually target a unilateral healing function and are unable to tackle the complexity and sensitivity of chronic refractory wound healing. This study fabricated a biomimetic nanozyme based on rhein (Cu-rhein NSs), which effectively mimics the activity of superoxide dismutase (SOD) for scavenging various free radicals. Additionally, zinc oxide microspheres (ZnO MSs) were prepared to enhance the antibacterial activity and mechanical properties of the modified hydrogel. Cu-rhein NSs and ZnO MSs were comodified onto an extracellular matrix-mimetic dual-network smart hydrogel constructed from oxidized sodium alginate, gelatin, and borax via dynamic borate and Schiff base bonds. The smart hydrogel presented the good biocompatibility and targeted the unique acidic microenvironment with high oxidative stress of chronic refractory wounds, intelligently releasing bionic nanozymes to effectively eliminate bacteria, reduce inflammatory responses, and scavenge multiple free radicals for reducing ROS. In vivo experiments on the rat model based on diabetic infection showed that the smart hydrogel could effectively eliminate bacteria, promote vascular regeneration and collagen deposition, reduce inflammatory response, and accelerate the healing of diabetic-infected wounds (almost complete healing within 14 days). The advantages of an intelligent, biomimetic tissue regeneration cascade management strategy against diabetic infected wound healing are highlighted.

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.

Hybrid Hydrogels of Polyacrylamide and Self-assembly Photodynamic Nanoparticles with Diverse Adhesion for Infected Chronic Wound Healing.

The healing of infected wounds is challenging for patients. In this paper, a hybrid hydrogel with strong tissue adhesion, self-healing, and antibiosis without antibiotics was developed as a dressing to promote the healing of infected chronic wounds. Acrylamide (PAM) was polymerized with N,N-methylene bis(acrylamide) (BIS) as the substrate, and self-assembled nanoparticles of carboxymethyl chitosan and chlorin e6 (CMCS/Ce6 NPs) trapped with magnesium (Mg2+) ions were dispersed in the hydrogel substrate. CMCS/Ce6 NPs provided favorable photodynamic antibiosis via the production of reactive oxygen species (ROS) under NIR irradiation. The hybrid hydrogels exhibited excellent self-healing properties, diverse adhesion, and biocompatibility. The in vivo results indicated that the hybrid hydrogel accelerated wound healing significantly via comprehensive factors of photodynamic antibiosis of CMCS/Ce6 NPs, cell proliferation promotion by Mg2+, good bioadhesion, and moisture retention of the PAM hydrogel, which promoted collagen deposition and blood vessel maturation.

Multifunctional carboxymethyl chitosan/oxidized carboxymethyl cellulose hydrogel loaded with ginsenoside Rg1 and polydopamine nanoparticles for infected diabetic wound healing

Besides bacterial infection, diabetic wounds are often accompanied by local inflammatory response, oxidative stress imbalances, and vascular formation disorders, which are the main reasons for long-term non-healing of diabetic wounds. In order to solve this problem, Ch-OCMC-PDA NPs-Rg1 self-healing hydrogel was constructed by Schiff base reaction. With the addition of PDA NPs and Rg1, Ch-OCMC-PDA NPs-Rg1 hydrogel showed excellent physical properties, like compressive strength of 142 kPa, swelling ratio of 148.91 %, and Rg1 carried in the hydrogel could achieve a slow release of 90.59 % within 48 h. What's more, PDA NPs endowed it with highly efficient photothermal antibacterial properties. In addition to excellent biocompatibility, Ch-OCMC-PDA NPs-Rg1 hydrogel could effectively clear intracellular reactive oxygen species, promote macrophages M2 transformation, and facilitate human umbilical vein endothelial cells migration and tube formation. In vivo experiments exhibited that Ch-OCMC-PDA NPs-Rg1 hydrogel could reduce wound inflammation, stimulate early angiogenesis, promote collagen deposition, and shorten the healing process of diabetic infected wounds, and the wound healing rate was significantly increased compared with other groups, reaching 98.41 ± 0.31 %. In summary, the multi-functional dynamic Ch-OCMC-PDA NPs-Rg1 hydrogel provides a new possibility for the treatment of diabetic infection wounds.

Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing

Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds.Graphical

Photothermal-Induced Multimodal Antibacterial Dressing Comprising N-Halamine Hydrogel Loaded with Cow Dung Biochar for Infected Wound Healing.

Disposal of the cow dung pollutants arising from cattle farming threatens the environment and public safety in diverse ways. To date, researchers have worked on developing new pathways to control and manage cattle farming wastes, but most do not involve the reuse of these wastes. Herein, a cow dung biochar-modulated photothermal N-halamine hydrogel (i.e., PAN/CA/CoBC/pMAG-Cl) was designed for converting cow dung into biochar (CoBC), which was then coupled with a 3D interpenetrating hydrogel network to treat infected wounds. The PAN/CA/CoBC/pMAG-Cl hydrogel exhibited excellent synergistic antibacterial performance against 106 CFU·mL-1 Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) within 60 min. The bactericidal effect was multimodal, involving CoBC-based photothermal killing (i.e., temperature as high as 80.5 °C) after 808 nm near-infrared light irradiation for 10 min, contact killing through the strong oxidative characteristic of N-halamine (pMAG-Cl), and release killing via active halogens (i.e., Cl+) reinforced by the photothermal action of CoBC. The S. aureus-infected wound model in vivo demonstrated that the PAN/CA/CoBC/pMAG-Cl hydrogel worked as an ideal wound dressing, capable of resisting bacterial infection, accelerating the healing process, and promoting epithelial regeneration. This proposed strategy could indicate a new way for the disposal of cow dung pollutant and its reuse in antibacterial-associated applications.

Semi-Interpenetrating Hydrogel with Long-Term Intrinsic Antibacterial Properties Promotes Healing of Infected Wounds In Vivo.

Bacterial infections significantly deteriorate the process of wound healing. The wound dressings loaded with antimicrobials are widely used to reduce bacterial infections. However, release-based sterilization may increase the risk of drug resistance of bacteria and complicate translation. Thus, the development of long-term intrinsic antibacterial wound dressings is highly desirable. In this study, an intrinsic antibacterial hydrogel (PVA/PPG-HBPL) consisting of poly(vinyl alcohol) (PVA), poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate) (PPG), and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The mechanical properties of the PVA/PPG-HBPL hydrogel were enhanced by hydrogen bonding and semi-interpenetrating networks. It also possessed a favorable ability to absorb the wound exudates. The release of antibacterial HBPL was significantly decreased by the methods of cyclic freeze-thawing and covalent cross-linking during hydrogel fabrication, enabling the PVA/PPG-HBPL hydrogel with intrinsic and long-term antibacterial performance. The PVA/PPG-HBPL hydrogel dressing killed 99.9% of methicillin-resistant Staphylococcus aureus (MRSA) cultured on its surface without observable cytotoxicity in vitro. It observably shortened the healing process by 2 orders of magnitude of MRSA colonies compared with the control in the MRSA-infected full-thickness skin wound of rats in vivo even after being soaked in phosphate-buffered saline (PBS) for 21 days (PBS was changed every 3 days). The antibacterial hydrogels could kill wound bacteria in a timely manner, significantly reduce inflammatory cell infiltration, and promote neovascularization and collagen deposition.