NPWT is a type of therapy to help wounds heal. During the treatment, a device decreases air pressure on the wound. This can help the wound heal more quickly.
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The gases in the air around us put pressure on the surface of our bodies. A wound vacuum device (wound vac) removes this pressure over the area of the wound. This can help a wound heal in several ways. It can gently pull fluid from the wound over time. This can reduce swelling and may help clean the wound. It's unclear if it reduces bacteria. NPWT also helps pull the edges of the wound together. And it may stimulate the growth of new tissue that helps the wound close.
NPWT has several parts. A foam or gauze dressing is put directly on the wound. An adhesive film covers and seals the dressing and wound. A drainage tube leads from under the adhesive film and connects to a portable vacuum pump. This pump removes air pressure over the wound, along with any fluids that drain from the wound. It may do this constantly, or in cycles.
The dressing is changed every 24 to 72 hours. During the therapy, you&#;ll need to carry the portable pump everywhere you go.
You might need this therapy for a recent traumatic wound. Or you may need it for a chronic wound. This is a wound that is not healing properly over time. This can happen with wounds linked to diabetes. You may need NPWT if you&#;ve had a recent skin graft. And you may need it for a large wound. Large wounds often take a longer time to heal.
NPWT may help your wound heal more quickly by:
Draining excess fluid from the wound
Keeping your wound moist and warm
Helping draw together wound edges
Increasing blood flow to your wound
Decreasing redness and swelling (inflammation)
NPWT offers some other advantages over other types of wound care. It may decrease your overall discomfort. The dressings usually need changing less often and are easier to keep in place.
NPWT has some rare risks, such as:
Bleeding (which may be severe)
Wound infection
An abnormal connection between the intestinal tract and the skin (enteric fistula)
Proper training in dressing changes can help reduce the risk of these problems. Also, your healthcare provider will carefully evaluate you to make sure you are a good candidate for the therapy. Certain problems can increase your risk of complications and NPWT may not be used, such as:
Exposed organs or blood vessels
High risk of bleeding from another health problem
Wound infection
Nearby bone infection
Dead wound tissue
Cancer tissue
Fragile skin, such as from aging or longtime use of topical steroids
Allergy to adhesive
Very poor blood flow to your wound
Wounds close to joints that may reopen due to movement
Your healthcare provider will discuss the risks that apply to you. Make sure to talk with your provider about all of your questions and concerns.
You likely won&#;t need to do much to get ready for NPWT. In some cases, you may need to wait a while before having this therapy. For example, your healthcare provider may first need to treat an infection in your wound. Dead or damaged tissue may also need to be removed from your wound.
You or a caregiver may need training on how to use NPWT. This is done if you will be able to have your therapy at home. In other cases, you may need to have your therapy in a healthcare facility such as a wound clinic. If you or a caregiver will be doing the therapy, you&#;ll be trained on how to use the device.
Your healthcare provider will tell you if you need to do anything else to prepare for NPWT.
A healthcare provider will cover your wound with a foam or gauze wound dressing. An adhesive film will be put over the dressing and wound. This seals the wound. The foam connects to a drainage tube, which leads to a vacuum pump. This pump is portable. When the pump is turned on, it draws fluid through the foam and out the drainage tubing. The pump may run all the time, or it may cycle off and on. Your exact setup will depend on the specific type of wound vacuum system that you use.
How often your dressing is changed depends on your wound. It may be changed daily, or it may be changed more or less often. You or your caregiver may be trained to do this at home. Or it may be done by a visiting healthcare provider. In some cases, it may be done by a healthcare provider in a hospital or other facility (wound clinic). You may need to stay in a care facility if you have a large or severe wound.
Your healthcare provider may prescribe a pain medicine. This is to prevent or reduce pain during the dressing change.
Tell your healthcare provider right away if you have a fever or increased swelling or pain in your wound. Also tell them if there is blood or blood clots in the tubing or collection chamber of the device.
You will likely need to use NPWT for several weeks or months. During the therapy, you&#;ll need to carry the portable pump everywhere you go. Your provider will carefully keep track of your healing.
During this time, make sure you have good nutrition and get enough rest. This is required for proper wound healing and to prevent infection. Your provider can tell you more about how to ensure your nutrition during this time.
If you smoke, ask for help so you can stop. The toxic substances in cigarette smoke (especially nicotine, carbon monoxide, and hydrogen cyanide) greatly impair your body's ability to heal the wound.
Follow up with your healthcare provider if you have a health condition that led to your wound, such as diabetes. They can help you prevent future wounds.
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Interruption of the wound healing process due to pathogenic infection remains a major health care challenge. The existing methods for wound management require power sources that hinder their utilization outside of clinical settings. Here, a next generation of wearable self-powered wound dressing is developed, which can be activated by diverse stimuli from the patient&#;s body and provide on-demand treatment for both normal and infected wounds. The highly tunable dressing is composed of thermocatalytic bismuth telluride nanoplates (Bi 2 Te 3 NPs) functionalized onto carbon fiber fabric electrodes and triggered by the surrounding temperature difference to controllably generate hydrogen peroxide to effectively inhibit bacterial growth at the wound site. The integrated electrodes are connected to a wearable triboelectric nanogenerator (TENG) to provide electrical stimulation for accelerated wound closure by enhancing cellular proliferation, migration, and angiogenesis. The reported self-powered dressing holds great potential in facilitating personalized and user-friendly wound care with improved healing outcomes.
Here, we report the development of a wearable self-powered wound dressing that can be triggered by diverse stimuli from the patient&#;s body (mechanical motions and temperature gradient) and can provide on-demand treatment for both normal and infected wounds. The tailored dressing was fabricated by integrating a thermocatalyst and TENG into a single system, where the thermocatalyst controllably produces H 2 O 2 for in situ bacterial eradication, while the TENG locally generates ES to promote wound healing. The near&#;room temperature thermoelectric material bismuth telluride (Bi 2 Te 3 ) was used as a thermocatalyst owing to its high Seebeck coefficient and excellent physical properties ( 53 , 54 ). Under different temperature gradients, a mild amount (&#;10 μM) of H 2 O 2 is generated by Bi 2 Te 3 nanoplates (Bi 2 Te 3 NPs), which will not trigger any adverse effect in normal tissues but at the same time is highly effective for antibacterial function. The amount of H 2 O 2 produced by the thermocatalyst is controllable, resulting in antibacterial activity that can be easily modulated depending on the severity of the infection at the wound site. Owing to its multifunctional capabilities, a tunable treatment pathway of the as-prepared wound dressing regulated by the wound type was demonstrated in an in vivo animal model. In the case of normal skin wounds, the wound dressing was connected to an arch-shaped TENG (a-TENG) to generate pulsed EFs to accelerate wound recovery, whereas EF from the a-TENG were synergistically applied with Bi 2 Te 3 NPs activated under a temperature difference to inhibit bacteria and promote subsequent healing of the wound for effective treatment of infected wounds. The concept and results presented in this work provide an advanced and power-free strategy for repairing versatile wounds.
Bacterial growth in wound tissue is the most critical factor contributing to delayed healing due to the secretion of virulent enzymes, which destroys the host tissue and disrupts wound recovery ( 43 , 44 ). Therefore, it is crucial to develop synergistic treatment approaches into a single platform that can simultaneously impede bacterial growth and heal chronic wounds for timely patient recovery. Recently, several antibacterial strategies have been integrated with wound repair approaches that use the in situ generation of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (·OH), and superoxide (·O 2 &#; ) to produce oxidative stress and bacterial cell damage ( 45 , 46 ). Overall, H 2 O 2 is less reactive and more stable than other ROS ( 47 ). H 2 O 2 can be generated by different chemical methods, such as anthraquinone-catalyzed (48) and electrocatalytic reduction of oxygen or by physical methods, such as plasma ( 49 ), photocatalysis ( 50 ), and piezocatalysis ( 51 ). Photocatalysts and piezocatalysts have been widely explored to generate H 2 O 2 ; however, their round-the-clock performance is hindered because of the unavailability of light and suitable mechanical forces in the environment ( 52 ), thereby limiting their application in clinical scenarios. On the other hand, temperature is one of the most ubiquitous factors in our daily life, and temperature differences exist almost everywhere in our surrounding environment. Recently, the catalytic activity of thermoelectric materials, termed thermocatalysts, has been reported for H 2 O 2 generation owing to their temperature difference&#;induced electron-hole pair separation, paving the way for the development of excellent alternatives to traditional photocatalysts and piezocatalysts ( 52 ). By using the naturally existing temperature difference in the bacteria-infected wound bed, thermocatalysts can spontaneously produce H 2 O 2 in situ, which can immensely contribute to combating bacteria at the wound site for expedited wound healing.
Recently, triboelectric nanogenerators (TENGs) have emerged as promising self-powered platforms because of their compelling characteristics, such as light weight, flexibility, conformability, easy fabrication, and high energy conversion efficiency ( 22 &#; 24 ). TENGs can transform biomechanical energy from human movements into electricity, which has been used for myriad biomedical applications as a power source for medical devices ( 25 &#; 27 ), and sensors for monitoring physiological parameters, including heart rate ( 28 , 29 ), respiration rate ( 30 , 31 ), pulse ( 32 ), strain ( 33 ), and pressure ( 34 ). By further integrating stretchable electrodes such as laser-induced graphene foams ( 34 , 35 ), thermoplastic polyurethane nanofibers ( 36 ), and so on with TENGs, highly stretchable self-powered platforms can be developed, which can generate electricity by maintaining a conformal contact with the skin ( 37 ). These recent developments has stirred a lot of interest in using the TENGs as an on-body ES module for delivering therapeutic electrical impulses, particularly for wound healing ( 16 , 20 , 21 ) and bone regeneration ( 38 ). Despite encouraging developments, providing effective ES via TENG is often challenged in terms of the biocompatibility, wearability, conformability, durability, and inadequate functionalities ( 39 &#; 42 ). The intensity of the EF generated by wearable TENGs is not sufficient to heal complicated chronic wounds that are often infected with pathogenic bacteria.
With the advancement of the Internet of Things (IoT), the world has witnessed an ever-growing concept of point of care, which is defined by a more personalized and minimally invasive approach to health care with better health outcomes and higher patient convenience ( 1 &#; 3 ). The point-of-care paradigm usually comprises wearable medical devices integrated with flexible electronics to accomplish conformal contact with skin and has emerged as a unique solution for the monitoring and on-demand treatment of diseases such as chronic wounds ( 4 &#; 7 ). Recent advances in medical technology have yielded advanced treatment strategies for chronic wounds, such as hyperbaric oxygen therapy ( 8 ), ultrasound ( 9 ), electromagnetic therapy ( 10 , 11 ), negative pressure therapy ( 12 , 13 ), photothermal therapy ( 14 , 15 ), and electrical stimulation (ES) ( 16 , 17 ). In particular, ES has emerged as an indispensable tool for wound care owing to its noninvasive nature, minimal side effects, and simplicity of operation ( 16 , 18 ). Current modalities of therapeutic ES include high-voltage pulsed current (HVPC), low-intensity DC (LIDC), and high-frequency AC electric fields (ACEF), which require bulky extracorporeal devices and professional operators, necessitating patient hospitalization ( 6 , 19 , 21 ). Furthermore, such devices rely on an external power source, which restricts their capabilities because of the rigid structure, limited lifetime, and risks for environmental pollution ( 4 , 21 ). Owing to these challenges, it is becoming increasingly important to develop wearable and miniaturized self-powered devices for wound healing that can render a comfortable experience for the patients while being treated.
A multifunctional wound dressing responsive to temperature gradients and mechanical stimuli is proposed as an appealing strategy for personalized wound treatment. The layer-by-layer approach was used to design the multifunctional dressing, which typically comprised a thermocatalytic layer (i.e., Bi2Te3 NPs) and a mechanical energy harvesting layer [i.e., chitosan coated carbon fiber fabrics (CFFs)] (Fig. 1A). The layered dressing structure is mainly composed of two CFF-based electrodes (top and bottom) coated with chitosan hydrogel on the exterior side. Chitosan hydrogel was used as a triboelectric and encapsulation layer because of its excellent biocompatibility, bioabsorbability, and biodegradability. The developed dressing is highly flexible (Fig. 1B), thus offering substantial conformal contact with full-thickness wounds (1 cm by 1 cm2) created on the dorsal region of mice (Fig. 1C). The wound dressing was integrated by vertically assembling two chitosan/CFFs, and two strips of uncoated CFFs from each layer placed outside the wound area functioned as electrodes that were connected to the TENG for ES. The inner side of the bottom CFF electrode was coated with thermocatalytic Bi2Te3 NPs, which can be triggered by a temperature gradient. In our previous study, Bi2Te3 NPs generated electron-hole pairs in response to an applied temperature gradient to effectively catalyze the reduction of molecular oxygen into ROS, such as H2O2. The high-resolution transmission electron microscopy (HRTEM) image in Fig. 1D reveals that the Bi2Te3 material forms a hexagonal NP-like morphology. In addition, well-defined lattice fringes with an interatomic spacing of 0.22 nm corresponding to the (110) planes of Bi2Te3 were observed, as shown in fig. S1 (A and B). Moreover, a homogeneous distribution of Bi and Te in a single NP was observed from the elemental mapping results obtained from energy-dispersive x-ray spectroscopy (EDX) analysis (Fig. 1D). Furthermore, the X-ray diffraction (XRD) patterns shown in fig. S1C confirmed the highly crystalline nature of the as-formed Bi2Te3 NPs.
(A) Structural design of the wound dressing with Bi2Te3 NPs as the thermocatalytic layer, chitosan hydrogel as the encapsulation layer, and CFF as the electrodes. (B) Flexible nature of the wound dressing. (C) Implementation of the wound dressing on a full-thickness wound created on the dorsal region of mice. (D) HRTEM image and elemental mapping images of Bi2Te3 NPs. (E) Change in the surface potential of Bi2Te3 NPs probed by KPFM at different temperature gradients. (F) Mechanism of the wound dressing for healing normal and infected wounds. a.u., arbitrary units.
To evaluate the voltage generation in thermoelectric materials in the presence of a temperature difference, surface potential analysis was carried out by Kelvin probe force microscopy (KPFM) integrated with a thermal stage (Fig. 1E and fig. S2). In the absence of a temperature gradient (ΔT), i.e., ΔT = 0°C, Bi2Te3 NPs showed negligible surface potential (&#;0 mV); however, when ΔT was increased to 7° and 15°C, the surface potential values of Bi2Te3 NPs were markedly enhanced to 43 and 137 mV, respectively (fig. S2). A slightly lower surface potential value (121 mV) was recorded under negative temperature gradients (ΔT = &#;15°C), suggesting that voltage generation depends not only on the applied temperature difference but also on the varied Seebeck coefficient within different temperature ranges. When the Bi2Te3 NPs were subjected to a temperature gradient, the potential difference between the KPFM tip and sample increased compared to the thermal equilibrium condition due to the increased surface charges of Bi2Te3 NPs, ultimately leading to a decrease in the work function of the material. A field-emission scanning electron microscopy (FESEM) image of the chitosan layer revealed the porous structure of the wound dressing (fig. S3A). The elemental mapping showed a uniform spatial distribution of C and O in the chitosan layer (fig. S3, B and C). Moreover, the adhesiveness of the wound dressing was evaluated at varying relative humidity (RH) conditions using the standard lap-shear test (fig. S4A). A negligible decrease in the adhesive strength was observed at high RH of 70%, indicating that the as-fabricated wound dressing can maintain adequate contact with the wound tissue even in the presence of sweat (fig. S4B). The as-prepared self-powered wound dressing can also be fabricated into different morphologies to fit variable wound shapes, including the irregular ones, and can be easily adapted to distinct wound sites, which validates the highly customizable nature of the as-fabricated dressing (fig. S5, A and B). Subsequently, the self-powered wound dressing was used as a wearable device to treat both normal and infected wounds (Fig. 1F). Two on-demand treatment strategies have been demonstrated on the basis of the wound type. The electrical output from the TENG activates the wound dressing to accelerate the healing process, while the presence of a temperature gradient effectively catalyzes the production of H2O2 to eradicate bacteria from the wound site.
It has been reported that thermoelectric materials can efficiently facilitate electron-hole pair separation in response to a temperature gradient (52). The negative charge migrates from the hot side to the cold side of the Bi2Te3 NP, thus generating a potential difference between the two ends (Fig. 2A). As a result, both the valence and conduction bands bend across the material to catalyze the formation of ·O2&#; radicals from molecular oxygen. Subsequently, electrons from the conduction band of Bi2Te3 NP migrate to the solution to produce H2O2 (·O2&#; + e&#; + 2H+ &#; H2O2). Therefore, thermocatalytic generation of H2O2 from Bi2Te3 NP&#;coated wound dressings was evaluated at different temperature gradients (Fig. 2B). Obvious amounts of H2O2 (>0.5 μM) were generated under various thermal gradients (ΔT = &#;15°, 7°, and 15°C) even after 5 min of treatment. The results showed the time-dependent formation of H2O2. Expectedly, maximum H2O2 was generated at a positive temperature gradient (ΔT = 15°C, 4.4 μM), which is &#;2.2-fold higher than that at &#;15°C, mainly due to an abrupt increase in the surface potential, as seen in fig. S2. The negligible amount of H2O2 in the control (ΔT = 0°C) groups confirm that the catalytic reaction is governed only by the applied temperature difference (fig. S6A). Moreover, fig. S6B shows that the H2O2 generation efficiency of Bi2Te3 NP&#;coated dressings is 4.3-fold higher than that of uncoated dressings. Dose-dependent investigation revealed that the production of H2O2 was further improved as the amount of Bi2Te3 NPs increased (Fig. 2C and fig. S7). In addition, negligible effect of RH on the H2O2 generation was observed, which revealed the robust nature of the Bi2Te3 NP&#;functionalized wound dressings against humidity changes in real environments (fig. S8, A and B). Nevertheless, the best catalytic performance of Bi2Te3 NPs for H2O2 generation was obtained with a higher catalytic amount at an elevated temperature gradient. Owing to the ROS-generating capabilities, thermocatalytic Bi2Te3 NP&#;functionalized wound dressings were further used to inactivate bacteria and carry out self-powered disinfection (Fig. 2D). The antibacterial performance of the wound dressing was assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through a standard plate-counting method and live/dead bacterial assays. The agar plating images and their respective quantitative results showed that as the temperature gradient increased from 0° to 15°C, the survival rates of E. coli substantially decreased from 100 to 16%, respectively (Fig. 2, E and F). Similarly, applied temperature gradient&#;dependent inhibition of bacterial growth was demonstrated against S. aureus (Fig. 2G and fig. S9). SYTO 9/propidium iodide (PI) staining of E. coli was performed to evaluate the integrity of the bacterial cell membrane. E. coli suspension treated under different temperature gradients indicated a large number of dead bacteria only after 10 min, which further increased after 30 min (Fig. 2H). These results imply a direct relationship between the amount of H2O2 generated and the antibacterial performance. The superior bacteriostatic activity is attributed to the enormous amount of H2O2 produced by Bi2Te3 NPs at a higher temperature gradient. Furthermore, we demonstrated that the bacterial viability of E. coli and S. aureus at ΔT = 15°C was dependent on the Bi2Te3 NP loading concentration (fig. S10). The amount of H2O2 released from the dressing could be easily controlled by the external temperature gradient, Bi2Te3 NP loading concentration, and treatment time; thus, wound dressings were used for further in vivo studies to examine the potential of self-powered antimicrobial systems.
(A) Schematic illustration of the thermocatalytic mechanism for H2O2 generation under a temperature gradient created because of the applied temperature difference. (B) Generation of H2O2 by Bi2Te3 NPs under different temperature gradients at different time intervals. (C) Generation of H2O2 by different amounts of Bi2Te3 NPs at different time intervals at ΔT = 15°C. (D) Schematic representation of the antibacterial mechanism of Bi2Te3 NPs. (E and F) Antibacterial efficiency of Bi2Te3 NPs for Escherichia coli [E. coli; Gram-negative bacterium (E)] and Staphylococcus aureus [S. aureus; Gram-positive bacterium (F)] at various temperature gradients. (G) Plating results showing the concentration of E. coli after treatment at different temperature gradients. (H) Images of live (green fluorescence) and dead (red fluorescence) bacterial cells following different temperature gradients after 10 and 30 min of treatment. Scale bars, 100 μm. Results are plotted as means ± SD (n = 3).
Traditional plate-based TENGs are not able to achieve full contact separation when an external force is applied because of rigidity in triboelectric layers. To address this limitation, an arch-shaped (a-TENG) with dimensions of 2 cm by 2 cm operating in vertical contact-separation mode was fabricated using chitosan/glycerol film and polytetrafluoroethylene (PTFE) as triboelectric layers (Fig. 3A). While the chitosan/glycerol film also functioned as the electrode layer, aluminum was deposited on the back side of PTFE, which served as the conductive layer. Moreover, polyethylene terephthalate (PET) was used as the substrate for the design of the a-TENG. Owing to its simple fabrication process, flexibility, and durability, the as-designed a-TENG is suitable for in vivo applications. The working mechanism of the a-TENG is illustrated in Fig. 3B. Initially, the arch shape does not allow any contact between triboelectric layers; however, upon application of external force, triboelectric layers come in contact with each other, resulting in charge transfer between the two layers. Depending on their electron-donating ability, electrons are transferred from the chitosan/glycerol film to PTFE, resulting in positive and negative charges on the surface of the chitosan/glycerol film and PTFE, respectively. However, because of the balanced net charge, electron flow does not occur in the external circuit (Fig. 3B, i). Once the externally applied force is withdrawn, the triboelectric layers revert to their native arch-like structure, which then disrupts the electrical equilibrium and drives the electrons in the external circuit (Fig. 3B, ii). This process of electron flow continues until a new equilibrium state is achieved, and the two triboelectric layers are completely separated (Fig. 3B, iii). When the force is applied again, a negative potential difference is generated that facilitates electron flow in the opposite direction to achieve electrical neutrality (Fig. 3B, iv). Moreover, microstructures were patterned on the surface of the chitosan/glycerol film via the replica molding method to enhance the effective contact area, which boosted the triboelectric output (Fig. 3C). Furthermore, the output characteristics of the as-fabricated TENG were evaluated by using a linear motor operating at a frequency of 1 Hz to obtain a stable mechanical force. As shown in Fig. 3 (D and E), the output voltage and current of the as-fabricated a-TENG reached 25 V and 1 μA, respectively. The output characteristics of the a-TENG remained unaltered over a wide range of environmental humidity and temperature changes, which is crucial for in vivo studies (Fig. 3F and fig. S11). In addition, the output voltage and current under different external resistances from 10 kilohms to 10 gigohms were tested, as shown in Fig. 3G. The corresponding power output is displayed in Fig. 3H, which shows that the maximum power of 18 μW is achieved at 60 megohm. Furthermore, the wearability of the a-TENG was demonstrated by wrapping the device around the dorsal region of mice (fig. S12A and movie S1). In the resting state, the arch shape of the TENG remains intact; however, in the active state (walking or running), the dorsal region becomes elevated, allowing the chitosan/glycerol layer to contact PTFE to generate the triboelectric signal (fig. S12B). Regular discrete voltage peaks were observed with every step of mouse motion, verifying that continuous ES can be achieved through such motion (fig. S12C). In the calm state, no notable voltage signal was generated; however, as the mice started to walk, a voltage output of 6.5 V was detected, which was further increased in the running state (25 V), confirming the strong correlation between TENG performance and the motion of mice.
(A) Schematic showing the structure of the a-TENG. (B) Working mechanism of the a-TENG under an external force. (C) FESEM image of the chitosan/glycerol layer of the a-TENG. (D and E) Output voltage (D) and current (E) of the a-TENG when driven by a linear motor. (F) Output voltage of the a-TENG at different RHs. The output voltage of the a-TENG remains the same even at a higher RH. (G) Dependence of the voltage and current of the TENG under various external load resistances. (H) Output power generated by the a-TENG under different external load resistances.
Fibroblasts play vital roles in the wound healing process and are usually involved in the migration, proliferation, and degradation of fibrin clots and the production of new extracellular matrix (ECM) components and several cytokines. The influence of electrical stimuli from a-TENG on fibroblast cells was studied in vitro by examining cell proliferation and migration. In a typical experimental setup, the a-TENG was connected to a rectifier to transform the AC into DC signal, generating an output voltage of 25 V at a constant frequency of 1 Hz. It has been reported that compared to AC, DC-based electrical output assists in directional migration and enhances the rate of angiogenesis, which, in turn accelerates the wound healing process (55, 56). The poor performance of AC-induced EFs is probably attributed to the lack of polarity in the opposing terminals (57). As shown in Fig. 4A, a pair of Au foil electrodes was placed in a well of the cell plate in a parallel orientation and connected to the a-TENG. Subsequently, the effects of various parameters such as treatment time, distance between the electrodes, and type of electrode on cell proliferation were systematically investigated. Figure S13A shows a gradual increase in the cell proliferation rate, reaching 42% in 30 min, which decreased instantly upon further stimulation because of cell damage caused by the Joule healing effect, resulting from prolonged ES durations (58). An increase in the duration of ES shifted the optimal EF strength required for promoting cell proliferation to lower values. In contrast, no obvious change was recorded for the control and without a-TENG (w/o a-TENG) groups (fig. S13B). The strength of the EF determines the fate of cell death, which can be greatly influenced by adjusting the distance between two Au electrodes placed in each cell well. The cell proliferation rate was boosted up to 141.2% as the interelectrode distance increased to 6 mm (fig. S13C). However, at a reduced interelectrode distance, increased EF strength leads to a change in the local pH of the medium from neutral to acidic, causing denaturation of proteins and alternation of normal cell functions (59). As a result, cell proliferation is decreased with decreasing distance between the two electrodes, as shown in fig. S13D. The rate of cell proliferation was markedly decreased (&#;120%) by using an Au wire&#;based electrode system instead of Au foil at a constant interelectrode distance of 6 mm, likely due to the relatively smaller surface area of the wire electrodes. A larger surface area of the foil electrodes enhances the charge storage capacity, thereby injecting a greater number of charges into the cell medium during ES, which results in a superior proliferation effect. Under optimal conditions, fibroblast cells electrically stimulated by the TENG for three consecutive days were labeled with Calcein-AM for observation under a fluorescence microscope (Fig. 4B). In contrast to the control and w/o TENG groups, stimulated fibroblast cells showed a 41.2% increase in cellular growth (Fig. 4C). Pulsed ES induces fibroblast proliferation by activating the transforming growth factor&#;β1&#;extracellular signal&#;regulated kinase (TGFβ1-ERK) pathway, which up-regulates several growth factors and cytokines, such as fibroblast growth factor 2 (FGF2), Delta-like non-canonical Notch ligand 1 (Dlk1), and so on (60). The results also suggested negligible cytotoxicity of Au electrodes used for proliferating the fibroblasts for up to 3 days. In addition, the developed TENG boosted the migration of fibroblast cells within 36 hours in the direction of the applied EF, unlike comparative groups, which migrated in arbitrary orientations (Fig. 4D). Directional migration enables contraction force toward the scratch area, leading to wound closure at a faster rate. Relative to those of the control and w/o TENG groups, stimulated cells migrated twofold faster (Fig. 4E). Last, the in vitro cytotoxicity of the Bi2Te3 NP&#;coated wound dressings was evaluated after coincubation with fibroblast cells for 24 hours (fig. S14).
(A) Schematic representation showing the influence of ES on cell proliferation and migration. (B) Fluorescence images of fibroblasts after ES from a-TENG recorded on days 0 and 3. (C) Cell proliferation of fibroblasts after 3 days of a-TENG&#;based ES. (D) Cell migration images of fibroblasts after 36 hours of ES from the a-TENG. (E) Corresponding cell migration ratio of fibroblasts under ES compared to the control groups. Results are plotted as means ± SD (n = 4); *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0..
To demonstrate practicality, the wearable self-powered dressing was directly applied for in vivo wound healing applications. A full-thickness circular wound with a diameter of 8 mm was created on the dorsal region of the mice. The dressing was positioned on top of the wound area with two fabric electrodes placed on each side of the wound such that the generated EF was perpendicular to the wound direction (Fig. 5A). The electrodes incorporated within the dressing was connected to the two terminals of the TENG after passing through a rectifier bridge, which generated a DC EF that could penetrate the dermis and intensify the endogenous EF to accelerate wound healing. During the ES study, TENG was controlled by the linear motor to produce a consistent mechanical force that generated an output voltage of 25 V at 1 Hz, which was conveyed to the wound dressing using conductive wires (Fig. 5B and fig. S15). To monitor the healing process, photographs of the wound area were captured at different time intervals over the course of 12 days (Fig. 5C). In the presence of an EF generated by the TENG, the wound area progressively contracted to 71.59% along the EF direction, compared to that of the control (92.4%) and w/o a-TENG (91.9%) groups, on day 3 (Fig. 5D). After day 12, TENG-treated wounds were completely recovered (&#;11%), while the relative wound closure area for the control and w/o a-TENG groups was still &#;31%. Hence, it was inferred that the pulsed DC output from the a-TENG directed the cells unidirectionally toward the center of the wound from the edges, resulting in enhanced wound closure along the EF direction. Furthermore, we investigated the role of thermocatalyst Bi2Te3 NPs in the self-powered wound repair process, in which ES and a temperature gradient were simultaneously applied to activate the wound dressing. As shown in fig. S16 (A and B), no obvious difference in wound contraction was observed between the a-TENG (10.8%) and a-TENG+ ΔT (12.1%) groups, implying that the thermocatalyst did not contribute to wound healing. Thus, it was deduced that ES from the a-TENG is mainly responsible for the repair of normal skin wounds.
(A) Schematic representation of wound dressing stimulated by the electrical output from a-TENG. (B) Schematic diagram of the experimental process throughout the 12-day period. (C and D) Digital photographs (C) and corresponding wound contraction area (D) of wounds taken on days 0, 3, 6, 9, and 12 for the control, w/o a-TENG, and w/ a-TENG groups. (E) H&E, Masson&#;s trichrome, and immunofluorescence staining for CD31 in wounds on day 12 following various treatments. (F and G) Quantitative results concerning the thickness of the epidermis (F) and collagen density in the dermal layer (G) of wounds on day 12 following various treatments. Results are plotted as means ± SD (n = 6); *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0..
To validate the efficiency of TENG-based ES for wound tissue regeneration, histological assessment was carried out by collecting tissue samples from the wound site on day 12. The hematoxylin and eosin (H&E) staining images shown in Fig. 5E indicate the existence of a scab (green arrow) on the wound area for the untreated control and w/o TENG groups, whereas scab formation is not evident for the a-TENG group. Moreover, the TENG group showed an intact epidermis (black arrow) around the regenerated tissues, which was ~2.8 times thicker than that in the control and w/o a-TENG groups (Fig. 5F). Furthermore, Masson&#;s trichrome staining was performed to analyze the collagen deposition (blue-stained area) in the dermal layer of the wounds, which is an important indicator of tissue remodeling. High density of orderly arranged collagen fibers (yellow arrow) in the dermal layer was observed in wounds treated with ES (Fig. 5E). Quantitative analysis revealed that the a-TENG&#;based ES enhanced the collagen deposition by ~2.6 times compared to other control groups (Fig. 5G). The electrical output from TENG up-regulates the production of collagen, a key structural constituent of granulation tissue, which strengthens the ECM of the newly formed connective tissue. In addition, compared to the control groups, a-TENG treatment increased the fluorescence intensity of CD31 by ~2.7-fold, which further supports the occurrence of ES-induced enhanced angiogenesis and rapid wound recovery (Fig. 5E and fig. S17). These analytical data demonstrate that ES from the a-TENG promotes cellular responses such as fibroblast proliferation and migration and amplifies angiogenesis whichgreatly acceleratesthe biological process of wound repair relative to that of the non-stimulated groups.
In addition to the electroactive layer, the hybrid wound dressing was functionalized with thermocatalytic Bi2Te3 NPs that displayed remarkable antibacterial efficiency in vitro. Hence, the wearable self-powered dressing was further used as an in situ platform to treat bacteria-infected wounds (Fig. 6A). A full-thickness wound (diameter, 8 mm) was created on the backs of the mice and incubated with S. aureus [1 × 106 colony-forming units (CFUs)/ml] to induce infection. After 24 hours, the wound infection model was established, and the wound dressing was placed at the infectious site with the two electrodes touching the edges of the wound bed (Fig. 6B). To trigger the desired function of the hybrid dressing, different stimuli were provided, and their effect on the microbial inhibition and wound repair process was examined. The TENG groups showed a ~32.1% relative wound closure area, which was three times lower than that in normal wounds after day 12 (Fig. 6C). Moreover, the healing performance of the electrically stimulated wound dressing was almost the same as that in the control and w/o a-TENG groups. The poor healing performance of the a-TENG group toward infected wounds emphasized the need for activating the thermocatalyst in the wound dressing. In contrast to those in the control (45.1%), w/o a-TENG (39.1%), and a-TENG (32.2%) groups, wounds treated under dual stimuli (a-TENG+ ΔT) recovered fully on the 12th day (Fig. 6D). Moreover, the antimicrobial performance of the wound dressings was assessed by culturing the biofluids swabbed from the wound site before and after treatment through standard lysogeny broth (LB) agar plating methods (Fig. 6E). Representative colony formation assays revealed that the hybrid treatment strategy (i.e., a-TENG+ ΔT) resulted in the inhibition of &#;86.7% of S. aureus on day 9; however, the control (~64.9%), w/o a-TENG (~59.2%), and a-TENG (~56.3%) groups displayed substantial bacterial growth (Fig. 6F). Complete eradication of S. aureus was achieved on day 12 in the a-TENG+ ΔT group. Although the thermal gradient primarily contributed to S. aureus elimination from the wound site, a negligible effect was observed in wound healing (figs. S18 and S19). Similarly, the wound dressing under hybrid a-TENG+ ΔT treatment was also most effective against E. coli&#;infected wounds (figs. S20 and S21). Therefore, it is imperative to trigger thermocatalytic and triboelectric layers at the same time to initiate microbial inhibition via H2O2 generation and promote tissue regeneration by ES from the TENG.
(A) Schematic representation of wound dressing stimulated by a-TENG and thermocatalyst for healing infected wounds. (B) Schematic diagram of the experimental process throughout the 12-day period. (C and D) Digital photographs (C) and corresponding wound contraction areas (D). (E and F) Agar plating images (E) and survival rates of bacterial cells (F) collected from the wound area for different treatment groups of infected wounds taken on days 0, 3, 6, 9, and 12 for the control, w/o a-TENG, w/ a-TENG, and a-TENG+ ΔT groups. (G and H) H&E, Masson&#;s trichrome, and IL-6 staining of control (G) and a-TENG+ ΔT (H) groups. (I and J) Quantitative results concerning the thickness of the epidermis (I) and the collagen density (J) in wounds on day 12. Results are plotted as means ± SD (n = 6); *P < 0.05, **P < 0.01, ***P< 0.001, and ****P < 0..
Furthermore, histological evaluation was performed on tissue sections excised from S. aureus&#;infected wounds before and after treatment with different strategies. The H&E staining images and its quantitative analysis reveal that the thickness of the epidermis formed in the wound treated with a-TENG+ ΔT was notably higher (139.8 μm) than that in the control (33.4 μm), w/o a-TENG (40.3 μm), and a-TENG (55.3 μm) groups (Fig. 6, G to I). Rapid healing of infected wounds under simultaneous temperature gradient and ES was also attributed to the higher density of collagen fiber deposition in the dermal layer, as quantified by Masson&#;s trichrome staining (Fig. 6, G and H, and fig. S22). Under the hybrid (a-TENG+ ΔT) treatment, the collagen deposition was increased by ~1.8 times compared to only w/ a-TENG group (Fig. 6I). Similarly, thicker epidermis and higher density of collagen deposition in the dermal layer was also observed for the E. coli&#;infected wounds after undergoing the hybrid treatment compared to other groups (fig. S23). In addition, the severity of wound infection is often associated with the increased secretion of pro-inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor&#;α (TNF-α). Particularly, IL-6 is considered as an important marker for diagnosis of clinical bacterial infections (61). Hence, immunofluorescence staining of IL-6 and TNF-α was performed to evaluate the infection levels and healing status of the wounds. As shown in Fig. 6 (G and H) and fig. S24, the expression of IL-6 was reduced by ~1.7 times under hybrid treatment, compared to the control groups, which suggests reduced infection promoting the wound recovery. Similarly, negligible expression of TNF-α was also observed for the wounds treated with a-TENG+ ΔT strategy (fig. S25). The comparative analysis indicated that the percentage of reduction of TNF-α and IL-6 expression in our study by day 9 is similar to the recently reported literatures (62, 63). For instance, Guo et al. in have reported that their microneedle-based wound dressing can reduce the IL-6 secretion by 1.8 times by day 9. Moreover, increased wound infection levels were associated with the increased secretion of IL-6 and TNF-α, whereas reduced infection levels led to the negligible expression of such pro-inflammatory factors, which is also evident from our results. Furthermore, fluorescence intensity of CD31 under hybrid treatment was 2.45, which was notably higher than the control groups (fig. S26), suggesting that higher neovascularization facilitated enhanced angiogenesis. The superior antimicrobial action and wound healing rate are ascribed to thermocatalytic Bi2Te3 NPs and TENG-driven ES, respectively. All these results confirmed that the integrated wound dressing repaired the infected wound by inhibiting bacterial growth via thermocatalysts, followed by on-demand treatment by ES from the a-TENG, which promoted angiogenesis and tissue regeneration, resulting in superior healing performance. The controllable nature of the self-powered wound dressing was demonstrated, and the treatment strategy can be reconfigured on the basis of the wound status.
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