Electrospun antibacterial nanofibers for wound dressings and tissue medicinal fields:A Review

Bacterial infections are a major cause of chronic infections.Thus,antibacterial material is an urgent need in clinics.Antibacterial nanofibers,with expansive surface area,enable efficient incorporation of antibacterial agents.Meanwhile,structure similar to the extracellular matrix can accelerate cell growth.Electrospinning,the most widely used technique to fabricate nanofiber,is often used in many biomedical applications including drug delivery,regenerative medicine,wound healing and so on.Thus,this review provides an overview of all recently published studies on the development of electrospun antibacterial nanofibers in wound dressings and tissue me-dicinal fields.This reviewer begins with a brief introduction of electrospinning process and then discusses electrospun fibers by incorporating various types of antimicrobial agents used as in wound dressings and tissue.Finally,we finish with conclusions and further perspectives on electrospun antibacterial nanofibers as 2D biomedicine materials.

A comparative study of two porous sponge scaffolds prepared by collagen derived from porcine skin and fish scales as burn wound dressings in a rabbit model

Collagen is widely used in biomedical applications due to its outstanding properties.In this study,highly porous sponge scaffolds were developed by using porcine skin-derived collagen(PSC)and fish scale-derived collagen(FSC),respectively.The morphology and composition of these PSC and FSC scaffolds were compared.The water uptake ratio of FSC scaffolds reached 47.8,which is 1.7 times of PSC scaffolds.The water vapour transmission rates(WVTR)of PSC and FSC scaffolds were 952.6655.5 and 1090.9677.1 g/m2/day,which could produce a moist healing environment for wounds.Both scaffolds show non-toxicity to L929 fibroblast cells.The burn wound healing efficiency of these two scaffolds was examined in vivo using rabbits.No scars around the wounds were observed after applying PSC and SFC scaffolds.Histopathological studies reveal that the wound treated with PSC and FSC scaffolds showed much better wound recovery than gauze and vaseline gauze groups.It was suggested that FSC scaffolds have great potential as same as PSC to be used as burn wound dressing materials.

Pre-clinical evaluation of soybean-based wound dressings and dermal substitute formulations in pig healing and non-healing in vivo models

In the last decade,a new class of natural biomaterials derived from de-fatted soybean fl our processed by either thermoset or extraction procedures has been developed.These biomaterials uniquely combine adaptability to various clinical applications to proven tissue regeneration properties.In the present work,the biomaterials were formulated either as hydrogel or as paste formulation and their potential as wound dressing material or as dermal substitute was assessed by two in vivo models in pig skin:The healing full-thickness punch biopsy model and the non-healing full-thickness polytetrafl uoroethylene(PTFE)chamber model.The results clearly show that collagen deposition is induced by the presence of these biomaterials.A unique pattern of early infl ammatory response,eliciting neutrophils and controlling macrophage infi ltration,is followed by tissue cell colonization of the wound bed with a signifi cant deposition of collagen fi bers.The study also highlighted the importance in the use of optimal formulations and appropriate handling upon implantation.In large size,non-healing wounds,wound dermis was best obtained with the paste formulation as hydrogels appeared to be too loose to ensure lasting scaff olding properties.On the contrary,packing of the granules during the application of paste reduced biomaterial degradation rate and prevent the penetration of newly vascularized tissue,thus impeding grafting of split-thickness autologous skin grafts on the dermal substitute base.

Electroactive and antibacterial wound dressings based on Ti_(3)C_(2)T_(x)MXene/poly(ε-caprolactone)/gelatin coaxial electrospun nanofibrous membranes

Endogenous electric fields(EFs)are capable of regulating the behaviors of skin cells in wound healing.However,majority of current dressings are primarily engaged in the passive repair of defective tissue,as they lack the ability to actively respond to physiological electrical signals.In this work,a series of nanofibrous membranes(NFMs)were fabricated by coaxial electrospinning,combining the good mechanical properties of poly(ε-caprolactone)(PCL),the bioactivity of gelatin and the electroactivity of Ti_(3)C_(2)T_(x)MXene,as electroactive and antibacterial dressings for cutaneous wound healing.The obtained NFMs exhibited suitable mechanical properties and hydrophilicity,excellent electroactivity,antibacterial activity,and biocompatibility.Especially,Ti_(3)C_(2)T_(x)MXene/PCL/gelatin-6(MPG-6,6 wt.%of Ti_(3)C_(2)T_(x)MXene in sheath spinning liquids)showed the optimal conductivity and antibacterial activity.Excitingly,this scaffold significantly promoted the adhesion,proliferation,and migration of NIH 3T3 cells under the electrical stimulation(ES).The in vivo evaluation in a full-thickness wounds defect model demonstrated that the MPG-6 films significantly accelerated wound closure,increased granulation tissue formation,increased collagen deposition,and promoted wound vascularization.In summary,the versatile scaffold is expected to be an ideal candidate as wound dressings due to its ability to promote the transmission of physiological electrical signals and thus improved the therapeutic outcomes of wound regeneration.

Commercial wound dressings for the treatment of exuding wounds:an in-depth physico-chemical comparative study

Background:Nowadays,a wide range of wound dressings is already commercially available.The selection of the dressing is of paramount importance as inappropriate wound management and dressing selection can delay the wound healing process.Not only can this be distressing for the patient,but it can also contribute to complications such as maceration and subsequent infection.Many researchers are targeting the design of dressings with superior properties over existing commercial dressings.However,reported results in the state-of-the-art are rarely benchmarked against commercial dressings.The aim of this study was to determine several characteristics of a large variety of the most frequently used commercial wound dressings,providing an overview for both practitioners and researchers.Methods:For this comparative study,11 frequently used commercial wound dressings were selected,representing the different types.The morphology was studied using scanning electron microscopy.The dressings were characterized in terms of swelling capacity(water,phosphate buffered saline and simulated wound fluid),moisture vapour transmission rate(MVTR)and moisture uptake capacity(via dynamic vapour sorption)as well as mechanical properties using tensile testing and texturometry.Results:The selected dressings showed distinctive morphological differences(fibrous,porous and/or gel)which was reflected in the different properties.Indeed,the swelling capacities ranged between 1.5 and 23.2 g/g(water),2.1 and 17.6 g/g(phosphate buffered saline)or 2.9 and 20.8 g/g(simulated wound fluid).The swelling capacity of the dressings in water increased even further upon freeze-drying,due to the formation of pores.The MVTR values varied between 40 and 930 g/m^(2)/24 h.The maximal moisture uptake capacity varied between 5.8%and 105.7%at 95%relative humidity.Some commercial dressings exhibited a superior mechanical strength,due to either being hydrophobic or multi-layered.Conclusions:The present work not only offers insight into a valuable toolbox of suitable wound dressing characterization techniques,but also provides an extensive landscaping of commercial dressings along with their physico-chemical properties,obtained through reproducible experimen-tal protocols.Furthermore,it ensures appropriate benchmark values for commercial dressings in all forthcoming studies and could aid researchers with the development of novel modern wound dressings.The tested dressings either exhibited a high strength or a high swelling capacity,suggesting that there is still a strong potential in the wound dressings market for dressings that possess both.

Polymeric hydrogels for burn wound care:Advanced skin wound dressings and regenerative templates

Wound closure represents a primary goal in the treatment of very deep and/or large wounds,for which the mortality rate is particularly high.However,the spontaneous healing of adult skin eventually results in the formation of epithelialized scar and scar contracture(repair),which might distort the tissues and cause lifelong deformities and disabilities.This clinical evidence suggests that wound closure attained by means of skin regeneration,instead of repair,should be the true goal of burn wound management.The traditional concept of temporary wound dressings,able to stimulate skin healing by repair,is thus being increasingly replaced by the idea of temporary scaff olds,or regenerative templates,able to promote healing by regeneration.As wound dressings,polymeric hydrogels provide an ideal moisture environment for healing while protecting the wound,with the additional advantage of being comfortable to the patient,due to their cooling eff ect and non-adhesiveness to the wound tissue.More importantly,recent advances in regenerative medicine demonstrate that bioactive hydrogels can be properly designed to induce at least partial skin regeneration in vivo.The aim of this review is to provide a concise insight on the key properties of hydrogels for skin healing and regeneration,particularly highlighting the emerging role of hydrogels as next generation skin substitutes for the treatment of fullthickness burns.

DEHYDRATION KINETICS OF POLYVINYL ALCOHOL HYDROGEL WOUND DRESSINGS DURING WOUND HEALING PROCESS

The hydrogel wound dressing based on polyvinyl alcohol （PVA） was prepared by the freezing-thawing cyclic method. The dehydration kinetics of prepared hydrogels was determined using the experimental method and mathematical modeling based on diffusion mechanism. The results show that the dehydration rate of PVA hydrogel wound dressing inversely depends on the hydrogel thickness as well as water content of the wound. On the other hand, the initial water content of hydrogel and the atmospheric humidity have little direct effect on the dehydration rate. The good agreement between experimental and mathematical modeling results in early stages of dehydration process shows that the predominate factor determining the dehydration of these wound dressings is diffusion.

Hydrogel wound dressings for diabetic foot ulcer treatment:Status-quo,challenges,and future perspectives

Diabetic foot ulcers(DFU)are a common and often debilitating complication of diabetes that can result in lower limb amputations if left untreated.Hydrogel dressings are three-dimensional networks of hydrophilic polymers that can absorb and retain large amounts of water,and have been shown to possess excellent biocompatibility,low toxicity,and excellent fluid handling properties.In addition,hydrogels create a moist wound environment that promotes wound healing by supporting cell proliferation,migration,and angiogenesis.Hydrogels,therefore,have emerged as promising wound dressings for promoting DFU healing.In this review,we attempt to chart the landscape of the emerging field of hydrogel as wound dressing for DFU treatment.We will explicitly review the assorted preparation methods for DFU hydrogels as well as a detailed discussion of various types of hydrogels deployed for DFU study.We also crystallize key findings,identify remaining challenges,and present an outlook on the future development of this enticing field.

Preparation of green cellulose diacetate-based antibacterial wound dressings for wound healing

Managing wounds is a growing universal problem and developing effective wound dressings to staunch bleeding and protect wounds from bacterial infections is an increasingly serious challenge.In this work,a remolding electrospinning nanofiber three-dimensional structure wound dressing(CCP)was prepared with superhydrophilicity,high water absorption and absorbing capacity,excellent hemostatic capacity and antibacterial ability,and biocompatibility to promote wound healing.Polyhexamethylene guanidine hydrochloride(PHMG)was grafted to cellulose diacetate(CDA)wound dressing surface through an amide reaction.A water contact angle analysis demonstrated that CCP wound dressing could be beneficial to promote wound exudate management effectively with rapid absorption of water within 0.2 s.In vitro hemo-and cytocompatibility assay showed that a CCP wound dressing had no significant hemotoxicity or cytoxicity.Specifically,CCP wound dressings could be beneficial to accelerate wound hemostasis and further reduce mortality caused by uncontrolled bleeding.Furthermore,CCP wound dressings have an excellent antibacterial ability,which could be beneficial to inhibit wound inflammatory over-reaction and promote normal wound healing.Combined together,the prepared wound dressing in this research effort is expected to have high-potential in clinical applications.

Heat preservation,antifouling,hemostatic and antibacterial aerogel wound dressings for emergency treatment

Hemostatic dressings with multiple functions are superior to current hemostatic dressings for use in the complex situation of emergency accidents.In particular,the existing dressings lack consideration for the prevention of hypothermic shock after massive hemorrhage.In this study,gelatin(GN)and oxidized pectin(OP)were used for Schiff base cross-linking,and then polyvinyl alcohol(PVA)solution mixed with hemostatic caffeic acid(CA)was introduced to obtain aerogel substrate material(CB)after lyophilization.Polydimethylsiloxane(PDMS)and silver nanowires(Ag NWs)were used to construct a hydrophobic layer,an antibacterial layer and an infrared reflective layer on both sides of CB to prepare a multifunctional aerogel wound dressing with heat preservation,antifouling,hemostasis and antibacterial properties(PDMS-Ag NW-CB).The results showed that the infrared transmittance of PDMS-Ag NW-CB is almost 0,so that thermal energy loss from the body is minimized.The contact angles with water and blood are 129°and 120°,respectively,which have the effect of antifouling.This dressing can absorb blood quickly within 10 min,adhere to and gather platelets,and achieve hemostasis.It has good antibacterial and biocompatibility.Therefore,PDMS-Ag NW-CB has great potential in application to emergency treatment.

Electrospun P(LLA-CL) Nanofibers Loaded with Vitamins E TPGS as Antibacterial Wound Dressing Materials

To obtain the wound dressings which can accelerate healing effectively,vitamin E D-α-Tocopherol polyethylene glycol succinate(vitamin E TPGS),one of the common derivatives of the unstable vitamins E,was successfully incorporated into P(LLA-CL)nanofibers by electrospinning.Electron microscopy showed that the smooth cylindrical fibers were obtained,albeit with a small amount of beading visible for the vitamins-loaded fibers.The diameters of the P(LLA-CL)fibers decreased with the addition of vitamins.The incorporation of the vitamin E TPGS in the electrospun fibers was confirmed by Fourier transform infrared spectroscopy(FTIR).Moreover,X-ray diffraction(XRD)indicated that vitamin E TPGS existed in the amorphous physical form after electrospinning.Fibers containing vitamin E TPGS showed a sustained release profile over more than 100 h in vitro.Antibacterial tests demonstrated that fibers loaded with vitamin E TPGS were effective in inhibiting the growth of E.coli and S.aureus.MTT assay showed that the fibers could promote the proliferation of L929 fibroblasts.These results above demonstrate the potential of P(LLA-CL)/vitamins E TPGS(P/E)as advanced wound dressing materials.

Molecular design, synthesis strategies and recent advances of hydrogels for wound dressing applications

With the changes in the modern disease spectrum,pressure ulcers,diabetic feet,and vascular-derived diseases caused refractory wounds is increasing rapidly.The development of wound dressings has partly improved the effect of wound management.However,traditional wound dressings can only cover the wound and block bacteria,but are generally powerless to recurrent wound infection and tissue healing.There is an urgent need to develop a new type of wound dressing with comprehensive performance to achieve multiple effects such as protecting the wound site from the external environment,absorbing wound exudate,anti-inflammatory,antibacterial,and accelerating wound healing process.Hydrogel wound dressings have the aforementioned characteristics,and can keep the wound in a moist environment because of the high water content,which is an ideal choice for wound treatment.This review introduces the wound healing process and the development and performance advantages of hydrogel wound dressings.The choice of different preparation materials gives the particularities of different hydrogel wound dressings.It also systematically explains the main physical and chemical crosslinking methods for hydrogel synthesis.Besides,in-depth discussion of four typical hydrogel wound dressings including double network hydrogels,nanocomposite hydrogels,drug-loaded hydrogels and smart hydrogels fully demonstrates the feasibility of developing hydrogels as wound dressing products and their future development trends.

Antibacterial biomaterials for skin wound dressing

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health.And bacterial contamination could significantly menace the wound healing process.Considering the sophisticated wound healing process,novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients,antibacterial agents included,into biomaterials with different morphologies to improve cell behaviors and promote wound healing.However,a comprehensive review on antibacterial wound dressing to enhance wound healing has not been reported.In this review,various antibacterial biomaterials as wound dressings will be discussed.Different kinds of antibacterial agents,including antibiotics,nanoparticles(metal and metallic oxides,lightinduced antibacterial agents),cationic organic agents,and others,and their recent advances are summarized.Biomaterial selection and fabrication of biomaterials with different structures and forms,including films,hydrogel,electrospun nanofibers,sponge,foam and three-dimension(3D)printed scaffold for skin regeneration,are elaborated discussed.Current challenges and the future perspectives are presented in thismultidisciplinary field.We envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.

Improving the Antibacterial Property of Chitosan Hydrogel Wound Dressing with Licorice Polysaccharide

A series of hydrogels with different ratios of chitosan and licorice polysaccharide(LP)were prepared by crosslinking to different concentrations of genipin(gp).They were characterized by FTIR(Fourier transform infrared spectroscopy),SEM(Scanning electron microscope),swelling ratio,rheological measurements,degradation with time,cytotoxicity,and antibacterial efficacy.Results show that the hydrogels have porous structures.With an increase in LP content,the swelling rate grows in the early stage of immersion in buffer and drops later.The swelling ratio ranged from 986%to 1677%,and stiffness varied from 777 Pa to 1792 Pa.The addition of LP reduced the mechanical strength and delayed gelation and degradation of the hydrogels.However,the most important discovery was that gp increases the viability of NIH 3T3 cells from 94%to 137%,and LP raises the bacteriostatic efficacy from 51%to 78%.Hydrogels synthesized from 1%genipin,3%chitosan,and 4%licorice polysaccharide showed the best antibacterial and fibroblast proliferation promoting activities.They exhibited moderate swelling and degradation rates over time,while being more suitable to affect healing of chronic wound infections.These results provide a new strategy to improve the antibacterial effectiveness and cyto-compatibility of chitosan hydrogels with water soluble active LPs from Glycyrrhiza that derive from traditional Chinese medicine.

Application of chitosan-based nanoparticles in skin wound healing

The rising prevalence of impaired wound healing and the consequential healthcare burdens have gained increased attention over recent years.This has prompted research into the development of novel wound dressings with augmented wound healing functions.Nanoparticle(NP)-based delivery systems have become attractive candidates in constructing such wound dressings due to their various favourable attributes.The non-toxicity,biocompatibility and bioactivity of chitosan(CS)-based NPs make them ideal candidates for wound applications.This review focusses on the application of CS-based NP systems for use in wound treatment.An overview of the wound healing process was presented,followed by discussion on the properties and suitability of CS and its NPs in wound healing.The wound healing mechanisms exerted by CS-based NPs were then critically analysed and discussed in sections,namely haemostasis,infection prevention,inflammatory response,oxidative stress,angiogenesis,collagen deposition,and wound closure time.The results of the studieswere thoroughly reviewed,and contradicting findings were identified and discussed.Based on the literature,the gap in research and future prospects in this research area were identified and highlighted.Current evidence shows that CS-based NPs possess superior wound healing effects either used on their own,or as drug delivery vehicles to encapsulate wound healing agents.It is concluded that great opportunities and potentials exist surrounding the use of CSNPs in wound healing.

Development of a poly(arylene sulfide sulfone)antibacterial electrospun film as a skin wound dressing application

Tissue engineering has become a hot issue for skin wound healing because it can be used as an alternative treatment to traditional grafts.Nanofibrous films have been widely used due to their excellent properties.In this work,an organic/inorganic composite poly(arylene sulfide sulfone)/ZnO/graphene oxide(PASS/ZnO/GO)nanofibrous film was fabricated with the ZnO nano-particles blending in an electrospun solution and post-treated with the GO deposition.The optimal PASS/ZnO/GO nanofibrous film was prepared by 2%ZnO nanoparticles,3.0g/mL PASS electrospun solution,and 1%GO dispersion solution.The morphology,hydrophilicity,mechanical property,and cytotoxicity of the PASS/ZnO/GO nanofibrous film were character-ized by using scanning electron microscopy,transmission electron microscope,water contact angle,tensile testing,and a Live/Dead cell staining kit.It is founded that the PASS/ZnO/GO nanofibrous film has outstanding mechanical properties and no cytotoxicity.Furthermore,the PASS/ZnO/GO nanofibrous film exhibits excellent antibacterial activity to both Escherichia coli and Staphylococcus aureus.Above all,this high mechanical property in the non-toxic and antibacterial nanofibrous film will have excellent application prospects in skin wound dressing.

Collagen/Chitosan Electrospun Nanofibrous Membrane for Wound Dressing

Collagen(Col)/chitosan(CS)nanofibrous membrane has great potential to be used as wound dressing.However,current Col/CS nanofibrous membrane produced from electrospinning can not offer sufficient mechanical strength for practical applications.Herein,a novel mixed solvent was used to prepare next-generation high-strength Col/CS nanofibrous membrane.Meanwhile,the optimal Col to CS weight ratio was investigated as well.The asproduced membrane was examined by scanning electron microscopy(SEM),attenuated total reflectance Fourier transform infrared spectroscopy(ATR-FTIR),differential scanning calorimetry(DSC),and XF-1A tester to study its morphological,chemical,thermal and mechanical properties.The preliminary results demonstrated that the mechanical properties of Col/CS nanofibrous membranes were enhanced substantially with the increase of CS weight ratios from 0 to 90%and the optimal Col to CS weight ratio was determined to be 1∶1.A promising way was presented to fabricate Col/CS electrospun nanofibrous membrane with sufficient mechanical strength for practical wound dressing applications.

Spatially engineering tri-layer nanofiber dressings featuring asymmetric wettability for wound healing

Inspired by the skin structure,an asymmetric wettability tri-layer nanofiber membrane(TNM)consisting of hydrophilic inner layer loaded with lidocaine hydrochloride(LID),hydrophobic middle layer with ciprofloxacin(CIP)and hydrophobic outer layer has been created.The hydrophobic outer layer endows the TNM with waterproof function and anti-adhesion from contaminants.The hydrophobic middle layer with CIP preserves long-term inhibition of bacteria growth and the hydrophilic inner layer with LID possesses optimal waterabsorbing capacity and air permeability.The TNM dramatically elevates the water contact angles from 10°
(inner layer)to 120
(outer layer),indicating an asymmetric wettability,which could directionally transport wound exudate within the materials and meanwhile maintain a comfortable and moist environment to promote wound healing.Furthermore,the sequential release of LID and CIP could relieve pain rapidly and achieve antibacterial effect in the long run,respectively.In addition,the TNM shows superior biocompatibility towards L929 cells.The in vivo results show the TNM could prevent infection,accelerate epithelial regeneration and significantly accelerate wound healing.This study indicates the developed TNM with asymmetrical wettability and synergetic drug release shows great potential as a wound dressing in clinical application.

A Promising Wound Dressing from Regenerated Silk Fibroin Sponge with Sustain-ed Release of Silver Nanoparticles

A silk fibroin(SF)spongy wound dressing incorporated with silver nanoparticles(Ag-NPs)was developed for biomedical applications.Ag-NPs were efficiently synthesized in situ via ultra violet(UV)with AgNO_(3) as precursor and silk fibroin as reducing and protecting agent,respectively.After lyophilization,the formed silk fibroin spongy wound dressing(SFWD)exhibited polyporous morphology and inner lamellae structures,with uniform dispersion of Ag-NPs.The porous structure provided SFWD with the ability to absorb tissue exudatealmost 6 times of its own weight,which could guarantee the sustained release of Ag-NPs.By methanol treatment,SFWD showed much improved mechanical properties and more stable to protease XIV.The cyto-compatibility of SFWD was supported by normal adherence and proliferation of NIH3T3 fibroblasts in sponges extracting culture medium.More important,the SFWD showed significant growth inhibition in both plate culture assays and bacterial suspension assays,with Gram-positive(Staphylococcus aureus)and Gram-negative(Pseudomonas aeruginosa and Escherichia coli).In a cutaneous excisional mouse model,the average healing rates of SFWD was significantly higher than control and commercial bandages.The hematoxylin-eosin(HE)staining results of the wound section also showed that SFWD could recruit more cells and promote tissue formation on the wound edges.

An Antibacterial Wound Dressing Based on GS-SF Composite Scaffold

Although the treatment of burn wounds has made great progress, the incidence of wound infection is still the main cause of high mortality. In this study, a silk fibroin (SF) scaffold wound dressing incorporated with Gentamicin Sulfate (GS) was developed for the treatment of burn infected wounds, in which GS was used as anti-bacterial agent. GS was mixed with silk fibroin solution and then processed into GS-SF composite scaffold via electro-spinning. The results showed the scaffold exhibited uniform polyporous morphology with 80% porosity. Induced by methanol, the scaffold presented much improved mechanical properties and stability to protease XIV. More important, the scaffold presented significant growth inhibition on both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria.