Multifunctional Dressings Research Articles

N-halamine modified ceria nanoparticles: Antibacterial response and accelerated wound healing application via a 3D printed scaffold

Antibacterial hydrogels are attracting extensive attention in soft tissue repair and regeneration. Herein, a novel three-dimensional (3D) printed dressing with prominent antibacterial activity and biocompatibility was fabricated based on gelatin methacryloyl (GelMA) via a photocrosslinking technique. As the main antibacterial components, CeO2/N-halamine hybrid nanoparticles (NPs) were added to the matrix of carboxymethylcellulose sodium (CMC)/xanthan gum. The 3D printed structure shows excellent shape fidelity and mechanical performance, which considerably enhances the swelling efficiency and blood-clotting ability of the dressings. Furthermore, the introduction of CeO2/N-halamine NPs endow the dressings with efficient antibacterial effect, and 99.6% Staphylococcus aureus and 99.8% Escherichia coli O157:H7 were inactivated when the contact time is up to 30 min. Notably, the fabricated dressings showed outstanding biocompatibility. In vivo experiments indicated that they efficiently accelerated wound closure by promoting the regeneration of dermis and epidermis tissues. This novel 3D printed antibacterial hydrogel might find applications as multifunctional dressings for wound treatments.

Peptidoglycan-inspired peptide-modified injectable hydrogels with enhanced elimination capability of bacterial biofilm for chronic wound healing

Majority of human infectious diseases is related to bacterial biofilm formation, especially the wound infection and delayed healing. Herein, recognizing peptide-modified polysaccharide based injectable hydrogel has been synthesized for effective anti-biofilm and infected wound healing. Inspiration from similar compatibility principle, the peptide (Alanine-glutamate-lysine-alanine), which is a part of the peptidoglycan, is grafted into the quaternized carboxymethyl chitosan （HTCC）for the first time. Afterwards, the quaternary ammonium salt groups in the synthetic injectable hydrogel cross-linked by the peptide modified quaternized carboxymethyl chitosan (HTCC-P) and oxidized dextran (OD), which can penetrate the bacterial cell wall and membrane under the recognition of peptide. Furthermore, the synergistic effect of quaternary ammonium salt groups and the peptide significantly enhance the anti-biofilm property of the hydrogels. In addition, the injectable hydrogel (HTCC-P/OD) cross-linked by Schiff base exhibits an excellent self-healing property and can completely cover the irregular wound shape. The cytotoxicity and in vivo wound healing also confirm the biocompatibility and capacity to accelerate tissue reconstruction of the hydrogels. Therefore, the hydrogels are expected to become competitive multifunctional dressings in biomedical field, including chronic wound infection and other bacterial biofilm related tissue repair.

Chitosan-based hydrogels with injectable, self-healing and antibacterial properties for wound healing

Developing an efficient and available material for improved cutaneous tissue regeneration is a major challenge in healthcare. Inspired by the concept of moist wound healing, the injectable and self-healing adenine-modified chitosan (AC) hydrogels are designed to significantly accelerate wound healing without the addition of therapeutic drugs. A series of AC derivatives with degree of substitution (DS) ranging from 0.21 to 0.55 were synthesized in aqueous solutions, and the AC hydrogels were prepared by a simple heating/cooling process. AC hydrogels presented good self-healing, low swelling rate capacity, biocompatibility, promote cell proliferation and excellent hemostatic effect. The hydrogels displayed excellent antibacterial activities against gram-negative bacteria, gram-positive bacteria, fungi and drug-resistance bacteria. Moreover, the full-thickness skin defect model experiments showed that AC hydrogels could reduce inflammatory cell infiltration and accelerate wound healing significantly. The hydrogel can shed new light on designing of the multifunctional dressings for wound healing.

Achieving effective patient outcomes with PolyMem® Silicone Border.

Clinicians are under increasing pressure to provide high-quality patient outcomes at a reduced cost. Increasingly, community staff must acquire knowledge on advanced wound care products to cope with the growing caseload demands. This article describes the use of PolyMem® dressings to reduce pain, inflammation, oedema and bruising and their ability to debride and absorb exudate while providing an optimum healing environment. The PolyMem range includes multifunctional dressings for various painful chronic wounds. This article also presents five case studies with particularly good patient outcomes where PolyMem dressings were the primary dressing. All five patients were holistically assessed to enable consistent evidence-based treatment decisions. In four cases, the new PolyMem Silicone Border dressing was used. The patients found the PolyMem Silicone Border dressing comfortable and gentle on removal even when the skin was extremely fragile. The right dressing used at the right time on the right patient can improve patient outcomes.

3D-printed scaffold composites for the stimuli-induced local delivery of bioactive adjuncts.

Polysaccharide scaffolds have been successfully employed to reconstruct environments that sustain skin tissue regeneration after injuries. Three-dimensional (3D) advanced additive manufacturing technologies allow creating scaffolds with controlled and reproducible macro- and micro-structure that improve the quality of the restored tissue to favor spontaneous repair. However, when persistent inflammation occurs, the physiological tissue healing capacity is reduced, like in the presence of pathologies like diabetes, vascular diseases, chronic infection, and others. In these circumstances, the bioavailability of therapeutic adjuncts like the growth factors in addition to the standard treatments represents undoubtedly a promising strategy to accelerate the healing of skin lesions. Precisely designed polysaccharide scaffolds obtained by 3D printing represent a robust platform that can be further implemented with the controlled delivery of bioactive adjuncts. Human elastin-like polypeptides (HELPs) are stimuli-responsive biopolymers. Their structure allows the integration of domains endowed with biological functionality, making them attractive compounds to prepare composites with smart properties. In the present study, 3D-printed alginate and chitosan scaffolds were combined with the HELP components. The HELP biopolymer was fused to the epidermal growth factor (EGF) as the bioactive domain. Different constructs were prepared and the stimuli-responsive behavior as well as the biological activity were evaluated, suggesting that these smart bioactive composites are suitable to realize multifunctional dressings that sustain the local release of therapeutic adjuncts.

Antibacterial hydrogel microparticles with drug loading for wound healing

Wound healing and regeneration are critical in medical care and pose a huge challenge for healthcare systems. It has great significance to develop functional materials for promoting wound repair. Herein, we presented novel antibacterial hydrogel microparticles with drug loading to treat the wound. The chitosan (CS) droplets were generated from a microfluidic electrospray system and solidified by sodium hydroxide solution. With further drying and drug uploading process, the drug-loaded CS microparticles (CSMPs) were achieved. The CSMPs exhibited excellent biocompatibility and antibacterial property, and displayed excellent capability in promoting wound healing in multiple stages. Hence, it is expected that the presented CSMPs can serve as multifunctional dressings for wound healing applications.

Multifunctional Injectable Hydrogel Dressings for Effectively Accelerating Wound Healing: Enhancing Biomineralization Strategy

AbstractBacterial infection can cause chronic nonhealing wounds, which may be a great threat to public health. It is highly desirable to develop an injectable wound dressing hydrogel with multifunctions including self‐healing, remodeling, antibacterial, radical scavenging ability, and excellent photothermal properties to promote the regeneration of damaged tissues in clinical practice. In this work, dopamine‐modified gelatin (Gel‐DA) is employed for the first time as a biotemplate for enhancing the biomineralization ability of gelatin to synthesize dopamine‐modified gelatin@Ag nanoparticles (Gel‐DA@Ag NPs). Further, the prepared Gel‐DA@Ag NPs with antioxidant activity and near‐infrared (NIR) laser irradiation synergistic antibacterial behavior are fixed in the guar gum based hydrogels through the formation of borate/didiol bonds to possess remolding, injectable, and self‐healing performance. In addition, the multifunctional hydrogels can completely cover the irregular wound shape to prevent secondary injury. More importantly, these hydrogel platforms under NIR can significantly accelerate wound healing with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that these hydrogels can serve as competitive multifunctional dressings in biomedical field, including bacteria‐derived wound infection and other tissue repair related to reactive oxygen species overexpression.

Sprayable hydrogel dressing accelerates wound healing with combined reactive oxygen species-scavenging and antibacterial abilities

Wound management poses a considerable economic burden on the global healthcare system, considering the impacts of wound infection, delayed healing and scar formation. To this end, multifunctional dressings based on hydrogels have been developed to stimulate skin healing. Herein, we describe the design, fabrication, and characterization of a sprayable hydrogel-based wound dressing loaded with cerium oxide nanoparticles (CeONs) and an antimicrobial peptide (AMP), for combined reactive oxygen species (ROS)-scavenging and antibacterial properties. We adopted a mussel-inspired strategy to chemically conjugate gelatin with dopamine motifs and prepared a hydrogel dressing with improved binding affinity to wet skin surfaces. Additionally, the release of AMP from the hydrogel demonstrated rapid release ablation and contact ablation against four representative bacterial strains, confirming the desired antimicrobial activities. Moreover, the CeONs-loaded hydrogel dressing exhibited favorable ROS-scavenging abilities. The biocompatibility of the multifunctional hydrogel dressing was further proven in vitro by culturing with HaCaT cells. Overall, the benefits of the developed hydrogel wound dressing, including sprayability, adhesiveness, antimicrobial activity, as well as ROS-scavenging and skin-remodeling ability, highlight its promissing translational potentials in wound management. Statement of SignificanceVarious hydrogel-based wound-dressing materials have been developed to stimulate wound healing. However, from the clinical perspective, few of the current wound dressings meet all the intended multifunctional requirements of preventing infection, promoting rapid wound closure, and minimizing scar formation, while simultaneously offering the convenience of application. In the current study, we adopted a mussel-inspired strategy to functionalize the GelMA hydrogels with DOPA to fabricate GelMA-DOPA hydrogel which exhibited an enhanced binding affinity for wound surfaces, AMP HHC-36 and CeONs are further encapsulated into the GelMA-DOPA hydrogel to confer the hydrogel wound dressing with antimicrobial and ROS-scavenging abilities. The GelMA-DOPA-AMP-CeONs dressing offered the benefits of sprayability, adhesiveness, antimicrobial activity, as well as ROS-scavenging and skin-remodeling ability, which might address the therapeutic and economic burdens associated with chronic wound treatment and management.

Electrospun Asymmetric Membranes as Promising Wound Dressings: A Review

Despite all the efforts that have been done up to now, the currently available wound dressings are still unable to fully re-establish all the structural and functional properties of the native skin. To overcome this situation, researchers from the tissue engineering area have been developing new wound dressings (hydrogels, films, sponges, membranes) aiming to mimic all the features of native skin. Among them, asymmetric membranes emerged as a promising solution since they reproduce both epidermal and dermal skin layers. Wet or dry/wet phase inversion, scCO2-assisted phase inversion, and electrospinning have been the most used techniques to produce such a type of membranes. Among them, the electrospinning technique, due to its versatility, allows the development of multifunctional dressings, using natural and/or synthetic polymers, which resemble the extracellular matrix of native skin as well as address the specific requirements of each skin layer. Moreover, various therapeutic or antimicrobial agents have been loaded within nanofibers to further improve the wound healing performance of these membranes. This review article provides an overview of the application of asymmetric electrospun membranes as wound dressings displaying antibacterial activity and as delivery systems of biomolecules that act as wound healing enhancers.

Hydrogel‐Based Multifunctional Dressing Combining Magnetothermally Responsive Drug Delivery and Stem Cell Therapy for Enhanced Wound Healing

AbstractMultifunctional dressings are attracting increased interest in the area of tissue engineering and regenerative medicine. Wound healing is a dynamic and complex process that requires multidisciplinary management. However, dressings that exhibit both anti‐infective and tissue regenerative properties are still limited. Herein, a hydrogel‐based multifunctional dressing weaved by drug‐loaded magnetothermally responsive [Fe3O4@SiO2‐interpenetrating polymer network (IPN)] microfibers and human umbilical cord mesenchymal stem cell‐laden microfibers is developed. Magnetothermally responsive microfibers, as smart constructs, can release antibiotics on‐demand to prevent infection, due to the magnetothermal heating effect of the embedded magnetic nanoparticles and the thermoresponsive property of the IPN hydrogels. Furthermore, stem cell‐laden microfibers markedly promote cell proliferation and tissue remodeling, with improved re‐epithelization, granulation tissue formation, and collagen deposition at the wound site. Hydrogel‐based microfibers have the additional ability of absorbing exudate, providing a moist environment, and retaining the therapeutic cells. Therefore, functional microfibers and textiles significantly accelerate the healing process. An advanced dressing for wound healing, incorporating controlled drug delivery and stem cell‐based therapy is developed. Furthermore, the results of the present study reveal the potential of multifunctional dressings in tissue engineering and regenerative medicine.

Physical Double‐Network Hydrogel Adhesives with Rapid Shape Adaptability, Fast Self‐Healing, Antioxidant and NIR/pH Stimulus‐Responsiveness for Multidrug‐Resistant Bacterial Infection and Removable Wound Dressing

AbstractDeveloping physical double‐network (DN) removable hydrogel adhesives with both high healing efficiency and photothermal antibacterial activities to cope with multidrug‐resistant bacterial infection, wound closure, and wound healing remains an ongoing challenge. An injectable physical DN self‐healing hydrogel adhesive under physiological conditions is designed to treat multidrug‐resistant bacteria infection and full‐thickness skin incision/defect repair. The hydrogel adhesive consists of catechol–Fe3+ coordination cross‐linked poly(glycerol sebacate)‐co‐poly(ethylene glycol)‐g‐catechol and quadruple hydrogen bonding cross‐linked ureido‐pyrimidinone modified gelatin. It possesses excellent anti‐oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self‐healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing‐assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin‐resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full‐thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on‐demand dissolvable and antioxidant physical double‐network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.

Novel ZnO/N-halamine-Mediated Multifunctional Dressings as Quick Antibacterial Agent for Biomedical Applications.

Cutaneous hemorrhage often occurs in daily life which may cause infection and even amputation. This research aims to develop a novel chitosan dressing impregnated with ZnO/N-halamine hybrid nanoparticles for quick antibacterial performance, outstanding hemostatic potential, high porosity, and favorable swelling property through combining sonication and lyophilization processing. After 30 days of storage, about 90% bacterial cell viability loss could be observed toward both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli O157:H7 within 30 min of contact by colony counting method. The hybrids assembled much more platelet and red blood cell as compared with pure chitosan control. Moreover, the lower blooding clotting index value gave evidence that these composites could control hemorrhaging and reduce the probability of wound infection. No potential skin irritation and toxicity were detected using in vitro cytocompatibility and a skin stimulation test. Therefore, this work demonstrated a facile and cost-effective approach for the preparation of N-halamine-based hybrid sponges which show promising application for wound dressings.

Superhydrophobic hierarchical fiber/bead composite membranes for efficient treatment of burns

One of the current challenges in burn wound care is the development of multifunctional dressings that can protect the wound from bacteria or organisms and promote skin regeneration and tissue reconstitution. To this end, we report the design and fabrication of a composite electrospun membrane, comprised of electrospun polylactide: poly(vinyl pyrrolidone)/polylactide: poly(ethylene glycol) (PLA:PVP/PLA:PEG) core/shell fibers loaded with bioactive agents, as a functionally integrated wound dressing for efficient burns treatment. Different mass ratios of PLA:PVP in the shell were screened to optimize mechanical, physicochemical, and biological properties, in addition to controlled release profiles of loaded antimicrobial peptides (AMPs) from the fibers for desirable antibacterial activity. Fibroblasts were shown to readily adhere and proliferate when cultured on the membrane, indicating good in vitro cytocompatibility. The introduction of PLA beads by electrospraying on one side of the membrane resulted in biomimetic micro-nanostructures similar to those of lotus leaves. This designer structure rendered the composite membranes with superhydrophobic property to inhibit the adhesion/spreading of exogenous bacteria and other microbes. The administration of the resulting composite fibrous membrane on burnt skin in an infected rat model led to faster healing than a conventional product (sterile silicone membrane) and control detailed herein. These composite fibrous membranes loaded with bioactive drugs provide an integrated strategy for promoting burn wound healing and skin regeneration. Statement of SignificanceTo address an urgent need in complex clinical requirements on developing a new generation of wound dressings with integrated functionalities. This article reports research work on a hierarchical fiber/bead composite membranes design, which combines a lotus-leaf-like superhydrophobic surface with drugs preloaded in the core and shell of fibers for effective burn treatment. This demonstrates a balance between simplified preparation processes and increased multifunctionality of the wound dressings. The creation of hierarchically structured surfaces can be readily achieved by electrospinning, and the composite dressings possessed a considerable mechanical strength, effective wound exudate absorption and permeability, good biocompatibility, broad antibacterial ability and promoting wound healing etc. Thus, our work unveils a promising strategy for the development of functionally integrated wound dressings for burn wound care.

Cobalt-mediated multi-functional dressings promote bacteria-infected wound healing

Wound dressings with multiple functions are required to meet the complexity of the wound healing process. The multifunctionality often leads to an increase in the complexity and difficulty in dressing preparation. To surmount this problem, we used a facile preparation and fabrication process to fabricate a multi-functional dressing by integrating four widely accessible materials: plain gauze, sodium alginate (SA), Ca2+ and Co2+. Firstly, mixed Ca2+/Co2+ ion solutions with different concentration were applied to gauzes. After drying, SA solution was added to ionized gauze and Co2+-Ca2+/Gauze/SA (Ion-GSA) composite dressings were formed easily. In vitro results showed that all Ion-GSA dressings exhibited strong mechanical properties, uniform dispersion and sustained release of Ca2+ and Co2+, and the ability to retain moisture and absorb wound exudate. Besides the above advantages, dressings prepared with 0.25 g/L Co2+ and 4 g/L Ca2+ (Co2+0.25-Ca2+4 GSA composite dressings) exhibited the best overall effect for inducing a hypoxia-like response, and favorable cytocompatibility, hemostatic property and antibacterial activity. In vivo wound healing assays revealed that Co2+0.25-Ca2+4 GSA composite dressings inhibited bacterial growth, increased local Hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) protein expression, and accelerated full-thickness skin wound healing in mouse bacterial-infected wound model. The quick healing wounds had improved angiogenesis, macrophages regulation, re-epithelialization and dense collagen deposition. Collectively, our results indicated that Co2+0.25-Ca2+4 GSA composite dressings promote wound healing. Statement of SignificanceWound dressings with integrated functionalities are required to meet complex clinical requirements. However, there is often a trade-off between reducing preparation complexity and increasing the multifunctionality of the dressing’s properties. In this study, we prepared multifunctional composite dressings by a facile preparation process using widely accessible materials. The composite dressings possessed the mechanical strength of gauze, had the effective wound exudate absorption, moisture maintenance and hemostatic property capacity of calcium alginate hydrogels, and had the hypoxia-like induction and the antimicrobial effects of Co2+. These functions all together promote bacteria-infected wound healing. Thus, we believed that the composite dressings can be widely applied in skin wound repair duo to their facile preparation method and good therapeutic effect.

Silver-pig skin nanocomposites and mesenchymal stem cells: suitable antibiofilm cellular dressings for wound healing

BackgroundTreatment of severe or chronic skin wounds is an important challenge facing medicine and a significant health care burden. Proper wound healing is often affected by bacterial infection; where biofilm formation is one of the main risks and particularly problematic because it confers protection to microorganisms against antibiotics. One avenue to prevent bacterial colonization of wounds is the use of silver nanoparticles (AgNPs); which have proved to be effective against non-multidrug-resistant and multidrug-resistant bacteria. In addition, the use of mesenchymal stem cells (MSC) is an excellent option to improve wound healing due to their capability for differentiation and release of relevant growth factors. Finally, radiosterilized pig skin (RPS) is a biomatrix successfully used as wound dressing to avoid massive water loss, which represents an excellent carrier to deliver MSC into wound beds. Together, AgNPs, RPS and MSC represent a potential dressing to control massive water loss, prevent bacterial infection and enhance skin regeneration; three essential processes for appropriate wound healing with minimum scaring.ResultsWe synthesized stable 10 nm-diameter spherical AgNPs that showed 21- and 16-fold increase in bacteria growth inhibition (in comparison to antibiotics) against clinical strains Staphylococcus aureus and Stenotrophomonas maltophilia, respectively. RPS samples were impregnated with different AgNPs suspensions to develop RPS-AgNPs nanocomposites with different AgNPs concentrations. Nanocomposites showed inhibition zones, in Kirby–Bauer assay, against both clinical bacteria tested. Nanocomposites also displayed antibiofilm properties against S. aureus and S. maltophilia from RPS samples impregnated with 250 and 1000 ppm AgNPs suspensions, respectively. MSC were isolated from adipose tissue and seeded on nanocomposites; cells survived on nanocomposites impregnated with up to 250 ppm AgNPs suspensions, showing 35% reduction in cell viability, in comparison to cells on RPS. Cells on nanocomposites proliferated with culture days, although the number of MSC on nanocomposites at 24 h of culture was lower than that on RPS.ConclusionsAgNPs with better bactericide activity than antibiotics were synthesized. RPS-AgNPs nanocomposites impregnated with 125 and 250 ppm AgNPs suspensions decreased bacterial growth, decreased biofilm formation and were permissive for survival and proliferation of MSC; constituting promising multi-functional dressings for successful treatment of skin wounds.

An Advanced Multifunctional Hydrogel‐Based Dressing for Wound Monitoring and Drug Delivery

Wound management is a major global challenge and poses a significant financial burden to the healthcare system due to the rapid growth of chronic diseases such as diabetes, obesity, and aging population. The ability to detect pathogenic infections and release drug at the wound site is of the utmost importance to expedient patient care. Herein, this study presents an advanced multifunctional dressing (GelDerm) capable of colorimetric measurement of pH, an indicator of bacterial infection, and release of antibiotic agents at the wound site. This study demonstrates the ability of GelDerm to detect bacterial infections using in vitro and ex vivo tests with accuracies comparable to the commercially available systems. Wireless interfaces to digital image capture hardware such as smartphones serve as a means for quantitation and enable the patient to record the wound condition at home and relay the information to the healthcare personnel for following treatment strategies. Additionally, the dressing is integrated within commercially available patches and can be placed on the wound without chemical or physical irritation. This study demonstrates the ability of GelDerm to eradicate bacteria by the sustained release of antibiotics. The proposed technology holds great promise in managing chronic and acute injuries caused by trauma, surgery, or diabetes.

Recent advances in electrospun nanofibers for wound healing.

Electrospun nanofibers represent a novel class of materials that show great potential in many biomedical applications including biosensing, regenerative medicine, tissue engineering, drug delivery and wound healing. In this work, we review recent advances in electrospun nanofibers for wound healing. This article begins with a brief introduction on the wound, and then discusses the unique features of electrospun nanofibers critical for wound healing. It further highlights recent studies that have used electrospun nanofibers for wound healing applications and devices, including sutures, multifunctional dressings, dermal substitutes, engineered epidermis and full-thickness skin regeneration. Finally, we finish with conclusions and future perspective in this field.