Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full‐Thickness Skin Regeneration During Wound Healing

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full‐thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid‐graft‐dopamine and reduced graphene oxide (rGO) using a H₂O₂/HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self‐healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full‐thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full‐thickness skin repair.     

In Situ Fabrication of Ultrasmall Gold Nanoparticles/2D MOFs Hybrid as Nanozyme for Antibacterial Therapy

As one of the common reactive oxygen species, H₂O₂ has been widely used for combating pathogenic bacterial infections. However, the high dosage of H₂O₂ can induce undesired damages to normal tissues and delay wound healing. In this regard, peroxidase‐like nanomaterials serve as promising nanozymes, thanks to their positive promotion toward the antibacterial performance of H₂O₂, while avoiding the toxicity caused by the high concentrations of H₂O₂. In this work, ultrasmall Au nanoparticles (UsAuNPs) are grown on ultrathin 2D metal–organic frameworks (MOFs) via in situ reduction. The formed UsAuNPs/MOFs hybrid features both the advantages of UsAuNPs and ultrathin 2D MOFs, displaying a remarkable peroxidase‐like activity toward H₂O₂ decomposition into toxic hydroxyl radicals (·OH). Results show that the as‐prepared UsAuNPs/MOFs nanozyme exhibits excellent antibacterial properties against both Gram‐negative (Escherichia coli) and Gram‐positive (Staphylococcus aureus) bacteria with the assistance of a low dosage of H₂O₂. Animal experiments indicate that this hybrid material can effectively facilitate wound healing with good biocompatibility. This study reveals the promising potential of a hybrid nanozyme for antibacterial therapy and holds great promise for future clinical applications.     

Microalgae-Based Biohybrid Microrobot for Accelerated Diabetic Wound Healing

A variety of wound healing platforms have been proposed to alleviate the hypoxic condition and/or to modulate the immune responses for the treatment of chronic wounds in diabetes. However, these platforms with the passive diffusion of therapeutic agents through the blood clot result in the relatively low delivery efficiency into the deep wound site. Here, a microalgae-based biohybrid microrobot for accelerated diabetic wound healing is developed. The biohybrid microrobot autonomously moves at velocity of 33.3 µm s⁻¹ and generates oxygen for the alleviation of hypoxic condition. In addition, the microrobot efficiently bound with inflammatory chemokines of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) for modulating the immune responses. The enhanced penetration of microrobot is corroborated by measuring fibrin clots in biomimetic wound using microfluidic devices and the enhanced retention of microrobot is confirmed in the real wounded mouse skin tissue. After deposition on the chronic wound in diabetic mice without wound dressing, the wounds treated with microrobots are completely healed after 9 days with the significant decrease of inflammatory cytokines below 31% of the control level and the upregulated angiogenesis above 20 times of CD31⁺ cells. These results confirm the feasibility of microrobots as a next-generation platform for diabetic wound healing.     

PEG修饰的镍钴层状双氢氧化物微球抗菌及溶血性能研究

双氧水作为常用的活性氧试剂广泛应用于清洗创面、去除痂皮、清洗带恶臭的创伤。但是由于其具有强烈刺激性,常采用表面涂抹的方式应用,不可注入体内。并且其常用的浓度高于生理水平,会对健康组织有一定毒性,甚至会延迟伤口愈合。为了解决这个问题,设计了一种利用聚乙二醇修饰的生物相容性好的镍钴层状双氢氧化物微球PEG-Ni/Co-LDHs,使得其具有较高的抑菌效果,同时能减少双氧水的用量。采用一步沉淀法合成了PEG-Ni/Co-LDHs,使用SEM、TEM、XRD等方法对PEG-Ni/Co-LDHs的结构进行表征,结果显示该材料的分散性能好,粒径约为470 nm,微球呈花状结构,由薄层似花瓣结构层层组装而成。PEG-Ni/Co-LDHs具有过氧化物酶的活性,这使得在双氧水的作用下能有效产生羟基自由基,高效抑制革兰氏阴性菌(大肠杆菌)和革兰氏阳性菌(金黄色葡萄球菌)增殖,高浓度时与双氧水联合作用,细菌成活率分别为32%和19%。采集大鼠血细胞对纳米材料PEG-Ni/Co-LDHs进行溶血性能研究,发现在高浓度时,其溶血率低于12%,未出现明显的溶血作用,具有很好的生物相容性。研究结果表明,PEG-Ni/Co-LDHs具有高抗菌活性和低溶血毒性的特点,为其今后作为抗菌剂在生物体内应用奠定了研究基础。     

Preparation,characterization, and in vivo evaluation of nano formulations of ferulic acid in diabetic wound healing

Diabetes mellitus is most common disorder characterize by hyperglycemia. Chronic hyperglycemia may lead to over production of free radicals thereby results in oxidative stress which impaired healing of wounds. Ferulic acid (FA) has been shown to have antidiabetic and antioxidant properties. The aim of the present study was to develop Ferulic acid nanoparticles and to study its hypoglycemic and wound healing activities. Ferulic acid-poly(lactic-co-glycolic acid) (FA-PLGA) nanoparticles were prepared by nano precipitation method. The prepared FA-PLGA nanoparticles had an average size of 240?nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed the prepared FA-PLGA nanoparticles were spherical in shape. Drug encapsulation assay showed that 88.49% FA was encapsulated in PLGA. Carbopol 980 was used to formulate FA-PLGA nanoparticles loaded hydrogel. FA-loaded polymeric nanoparticles dispersion (oral administration) and FA-loaded polymeric nanoparticles based hydrogel (topical administration) treated wounds were found to epithelize faster as compared with diabetic wound control group. The hydroxyproline content increased significantly when compared with diabetic wound control. Therefore, the results indicate that FA significantly promotes wound healing in diabetic rats.     

Effect of novel blend nanofibrous scaffolds on diabetic wounds healing

Chitosan‐poly (vinyl alcohol) (Cs: PVA) (2:3) and poly (caprolactone)‐chitosan‐poly (vinyl alcohol) (PCL: Cs: PVA) (2:1:1.5) nanofibrous blend scaffolds were fabricated using the electrospinning technique in the authors’ previous studies. The results of the previous studies confirmed the high biological properties of the scaffolds and their ability in healing of burn and excision wounds on rat model. In the present study, the biological scaffolds were applied on diabetic dorsum skin wounds and diabetic foot wound on rat models (n = 16). Macroscopic and microscopic investigations were carried out using digital images and haematoxylin and eosin (H&E) staining respectively, to measure the wound areas and to track wound healing rate. It was found that at all time points the areas of wounds treated with nanofibrous scaffolds were smaller compared with the controls. Pathological results showed much better healing efficacy for the test samples compared with the control ones. Pathological investigations proved the presence of more pronounced granulation tissues in the scaffold‐treated wounds compared with the control ones. At 20 days post excision, the scaffold‐treated groups achieved complete repair. The results indicated that Cs: PVA and PCL: Cs: PVA nanofibrous webs could be considered to be promising materials for burn, excision and diabetic wounds healing.Inspec keywords: wounds, diseases, biomedical materials, polymer blends, nanofibres, polymer fibres, nanomedicine, nanofabrication, electrospinning, skin, cellular biophysics, caesium, medical image processing, patient treatmentOther keywords: chitosan‐poly (vinyl alcohol), poly (caprolactone)‐chitosan‐poly (vinyl alcohol), nanofibrous blend scaffolds, electrospinning, biological properties, rat model, diabetic dorsum skin wound healing, diabetic foot wounds, rat models, digital imaging, H&E staining, pathology, granulation tissues, PCL‐Cs‐PVA nanofibrous webs, excision wound healings, burn wound healings     

Biomedical evaluation of a novel nitrogen oxides releasing wound dressing

Chronic wounds are a major cause for both suffering and economical losses. Management of chronic non-healing wounds requires multipronged approach. They are polymicrobial and agonizing for the patient due to associated pain. Moist dressing providing antimicrobial action is a highly desirable chronic wound management option. Here we report a hydrogel based dressing that possesses the antimicrobial properties of acidified sodium nitrite and the homeostatic property of a hydrogel. The dressing was developed by combining citric acid cross-linked cotton gauze and sodium nitrite loaded gelatin. The cotton gauze was cross-linked with citric acid by pad-dry-curing in presence of nano-titania catalyst. The cotton gauze-gelatin hydrogel combination was gamma-irradiated and freeze-dried. At the time of application, the freeze-dried dressing is wetted by sodium nitrite solution. The dressing has a fluid uptake ability of 90 % (w/v) and the water vapour evaporation rate was estimated to be 2,809 ± 20 g/m²/day. The dressing showed significant antimicrobial activity against both planktonic and biofilm forms and was effective during consecutive re-uses. Cytotoxicity study showed inhibition of fibroblasts, but to a lesser extent than clinically administered concentrations of antiseptic like povidone iodine. Storage at 37 °C over a 3 month period resulted in no significant loss of its antimicrobial activity.     

Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m²/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.     

Construction of Single‐Iron‐Atom Nanocatalysts for Highly Efficient Catalytic Antibiotics

Bacterial infection caused by pathogenic bacteria has long been an intractable issue that threatens human health. Herein, the fact that nanocatalysts with single iron atoms anchored in nitrogen‐doped amorphous carbon (SAF NCs) can effectively induce peroxidase‐like activities in the presence of H₂O₂, generating abundant hydroxyl radicals for highly effective bacterial elimination (e.g., Escherichia coli and Staphylococcus aureus), is reported. In combination with the intrinsic photothermal performance of the nanocatalysts, noticeable bacterial‐killing effects are extensively investigated. Especially, the antibacterial mechanism of critical cell membrane destruction induced by SAF NCs is unveiled. Based on the bactericidal properties of SAF NCs, in vivo bacterial infections propagated at wounds by E. coli and S. aureus pathogens can be effectively eradicated, resulting in better wound healing. Collectively, the present study highlights the highly efficient in vitro antibacterial and in vivo anti‐infection performances by the single‐iron‐atom‐containing nanocatalysts.     

Development of nanotechnology for advancement and application in wound healing: a review

Wound healing is a series of different dynamic and complex phenomena. Many studies have been carried out based on the type and severity of wounds. However, to recover wounds faster there are no suitable drugs available, which are highly stable, less expensive as well as has no side effects. Nanomaterials have been proven to be the most promising agent for faster wound healing among all the other wound healing materials. This review briefly discusses the recent developments of wound healing by nanotechnology, their applicability and advantages. Nanomaterials have unique physicochemical, optical, and biological properties. Some of them can be directly applied for wound healing or some of them can be incorporated into scaffolds to create hydrogel matrix or nanocomposites, which promote wound healing through their antimicrobial, as well as selective anti‐ and pro‐inflammatory, and proangiogenic properties. Owing to their high surface area to volume ratio, nanomaterials have not only been used for drug delivery vectors but also can affect wound healing by influencing collagen deposition and realignment and provide approaches for skin tissue regeneration.Inspec keywords: skin, wounds, cellular biophysics, drug delivery systems, tissue engineering, hydrogels, nanocomposites, proteins, nanomedicineOther keywords: wound healing materials, nanomaterials, nanotechnology, proangiogenic properties, proinflammatory properties, collagen deposition, drug delivery vectors, skin tissue regeneration     

Hydrogels containing rutin intended for cutaneous administration: efficacy in wound healing in rats

Objective: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats.

Methods: Hydrogels were prepared using Carbopol Ultrez^® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress.

Results and discussion: Hydrogels showed adequate pH values (5.50–6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels.

Conclusion: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing.     

A new HRP/catalase biosensor based on microconductometric transduction for nitrite determination

An interdigitated conductimetric electrode system using a combination of peroxidase/catalase has been developed to determine nitrite in water samples. A peroxidase (HRP) was located in the inner layer while the outer contained catalase. Catalase catalyzed the breakdown of H₂O₂ into H₂O and O₂ thus consuming totally H₂O₂, the substrate of HRP. The latter, in presence of H₂O₂, generates a conductometric signal due to the reduction of H₂O₂. Nitrite was selected as an inhibitor of catalase. In the presence of H₂O₂, the nitrite addition blocked the H₂O₂ consumption by catalase. Since nitrite had no effect on HRP activity, its inhibitive effect on catalase leads to an increase in the conductometric signal. The bienzyme sensor exhibits an increase in conductometric response for nitrite concentration, leading to high values of conductivity. In both case, the detection limit of nitrite is 0.3 µM and for bienzyme sensor the dynamic range is from 0.3 µM to 446 µM.     

Fabrication and electrochemical characterization of HRP-lipid Langmuir-Blodgett film and its application as an H2O2 biosensor

The formation of horseradish peroxidase-lipid Langmuir-Blodgett film and its applicability as a biosensor have been studied. HRP was spread directly onto the subphase covered with a layer of lipid in LB trough. Our experimental results showed that surface pressure of this film from liquid to solid state ranged between 15 to 25 mN/m. At surface pressure of 25 mN/m, the monolayer was successfully transferred onto the gold surface. In addition, electrochemical properties of this film showed that protein molecules still kept their natural structure and can give a well electrocatalytic activity to H₂O₂. As an H₂O₂ biosensor, this LB film was able to detect concentration of H₂O₂ which were 3 × 10^− 7 M.     

Thread‐Like Radical‐Polymerization via Autonomously Propelled (TRAP) Bots

Micromotor‐mediated synthesis of thread‐like hydrogel microstructures in an aqueous environment is presented. The study utilizes a catalytic micromotor assembly (owing to the presence of a Pt layer), with an on‐board chemical reservoir (i.e., polymerization mixture), toward thread‐like radical‐polymerization via autonomously propelled bots (i.e., TRAP bots). Synergistic coupling of catalytically active Pt layer, together with radical initiators (H₂O₂ and FeCl₃ (III)), and PEGDA monomers preloaded into the TRAP bot, results in the polymerization of monomeric units into elongated thread‐like hydrogel polymers coupled with self‐propulsion. Interestingly, polymer generation via TRAP bots can also be triggered in the absence of hydrogen peroxide for cellular/biomedical application. The resulting polymeric hydrogel microstructures are able to entrap living cells (NIH 3T3 fibroblast cells), and are easily separable via a centrifugation or magnetic separation (owing to the presence of a Ni layer). The cellular biocompatibility of TRAP bots is established via a LIVE/DEAD assay and MTS cell proliferation assay (7 days observation). This is the first study demonstrating real‐time in situ hydrogel polymerization via an artificial microswimmer, capable of enmeshing biotic/abiotic microobjects in its reaction environment, and lays a strong foundation for advanced applications in cell/tissue engineering, drug delivery, and cleaner technologies.     

Quaternary co-electrodeposition of the Cu2ZnSnS4 films as potential solar cell absorbers

Cu₂ZnSnS₄ (CZTS) films are successfully prepared on Mo substrate by electrochemical epitaxial method. An electrolyte contains 0.124 M CuSO₄·5H₂O, 0.14 M ZnSO₄, 0.13 M SnCl₂·2H₂O, 0.16 M Na₂S₂O₃·5H₂O, 2.25 M NaOH, 1.36 M C₆H₅Na₃O₇, 1.00 M C₄H₆O₆. The equilibrium potential for quaternary co-electrodeposited solution is set at ?1.1 ～ ?1.20 V. The results show that elements are deposited in the following sequence: Cu/S/Zn/S/Cu/S/Sn/S…. The ternary and quaternary compounds are formed with the increasing temperature during annealing. Finally the CZTS film can be well formed at 550 °C. The resistivity of CZTS is about 5.6 × 10⁴ Ω cm.     

Electrospinning: An emerging technology to construct polymer-based nanofibrous scaffolds for diabetic wound healing

A chronic wound in diabetic patients is a major public health concern withsocioeconomic and clinical manifestations.The underlying medical condition of diabeticpatients deteriorates the wound through physiological,metabolic,molecular,and cellularpathologies.Consequently,a wound enters a vicious pathological inflammatory cycle.Many therapeutic approaches are in practice to manage diabetic wounds hence ensuringthe regeneration process.Polymer-based biomaterials have come up with hightherapeutic promises.Many efforts have been devoted,over the years,to build aneffective wound healing material using polymers.The electrospinning technique,although not new,has turned out to be one of the most effective strategies in buildingwound healing biomaterials due to the special structural advantages of electrospunnanofibers over the other formulations.In this review,careful integration of allelectrospinning approaches has been presented which will not only give an insight intothe current updates but also be helpful in the development of new therapeutic materialconsidering pathophysiological conditions of a diabetic wound.     

Advanced nanofibrous textile-based dressing material for treating chronic wounds

In the present work, an electrospun nanofibrous textile composed of polyurethane (PU), sodium bicarbonate (\(\hbox {NaHCO}_{3}\)) and pantothenic acid (PA) is developed for treating chronic wounds. Wounds are a common health problem and in particular, the chronic wounds such as vascular ulcers, diabetic ulcers and pressure ulcers cause a large number of morbidity and mortality. The main problems of the chronic wounds are prolonged inflammation phase and presence of acidic environment. These events deactivate the operation of growth factors and also the progression of natural healing mechanism. Hence, various types of advanced textile-based dressings are developed to address the clinical complications associated with chronic wound management. The prepared electrospun scaffolds were characterized to study their physicochemical and haemocompatible properties. The scanning electron microscopy micrographs depicted continuous, smooth-interconnected nanofibrous morphology of PU–NaHCO\(_{3}\)–PA scaffolds. The Fourier transform infrared spectroscopy spectra indicated the addition of NaHCO\(_{3}\) and PA-based hydrophilic chemical groups, which significantly enhanced the wettability of the composites. Further, the PU–NaHCO\(_{3}\)–PA composite membrane inferred to have a highly porous structure with the mean porosity of 79.4 ± 4.8%, which may provide a conducive environment for adherence and proliferation of skin cells. The composite scaffold also offers a highly haemocompatible surface by delaying coagulation of blood through contact activation pathways and by limiting red blood cells damage. Therefore, the excellent physicochemical properties, blood compatibility and the delivery of PA are anticipated to speed up the impaired healing process of chronic wounds.     

Development of a novel porous cryo-foam for potential wound healing applications

This body of work describes the development of a porous hydrogel for wound healing applications. In the present study poly (vinyl alcohol) (PVA) and poly (acrylic acid) (PAA) based hydrogels were prepared, and their properties were examined. Varying concentrations of the polymers and distilled water were used to prepare the hydrogels. The use of a high shear mixer, for foaming the PVA and PVA/PAA gels, and how this physical change can affect the structure and porosity of the hydrogel in question, represents a key feature of this work. The mechanical and thermal properties were determined by parallel plate rheometry and modulated differential scanning calorimetry (MDSC) respectively. The results indicated that the hydrogels containing low concentration of PVA and high volume of H₂O are significantly weaker than those synthesised with higher concentrations of PVA. The thermal analysis shows distinct endotherms and provides evidence of crystallisation. The chemical structure of the hydrogels was confirmed by means of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR).     

Alginate membranes loaded with hyaluronic acid and silver nanoparticles to foster tissue healing and to control bacterial contamination of non-healing wounds

Chronic non-healing wounds are a clinically important problem in terms of number of patients and costs. Wound dressings such as hydrogels, hydrocolloids, polyurethane films and foams are commonly used to manage these wounds since they tend to maintain a moist environment which is shown to accelerate re-epithelialization. The use of antibacterial compounds is important in the management of wound infections. A novel wound-dressing material based on a blended matrix of the polysaccharides alginate, hyaluronic acid and Chitlac-silver nanoparticles is here proposed and its application for wound healing is examined. The manufacturing approach to obtain membranes is based on gelling, foaming and freeze-casting of alginate, hyaluronic acid and Chitlac-silver nanoparticles mixtures using calcium ions as the cross-linking agent. Comprehensive evaluations of the morphology, swelling kinetics, permeability, mechanical characteristics, cytotoxicity, capability to inhibit metalloproteinases and of antibacterial property were conducted. Biological in vitro studies demonstrated that hyaluronic acid released by the membrane is able to stimulate the wound healing meanwhile the metal silver exploits an efficient antibacterial activity against both planktonic bacteria and biofilms. Overall, the experimental data evidence that the studied material could be used as antibacterial wound dressing for wound healing promotion.

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Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing

A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were prepared by radiation crosslinking. A pre-clinical study was performed by implantation model and full-thickness cutaneous wound model in Sprague–Dawley rats to preliminarily evaluate the biocompatibility, biodegradability and effects on healing. In the implantation test, as a component of the hydrogels, CM-chitosan showed a positive effect on promoting cell proliferation and neovascularization, while gelatin was efficient to stabilize the structure and prolong the degradation time. To evaluate the function on wound healing, the hydrogels were applied to the relatively large full-thickness cutaneous wounds (Φ3.0 cm). Compared with the control groups, the hydrogel group showed significantly higher percentage of wound closure on days 9, 12 and 15 postoperatively, which was consistent with the significantly thicker granulation tissue on days 3 and 6. All results apparently revealed that the radiation crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue formation and accelerate the wound healing.