A Spray‐Filming Self‐Healing Hydrogel Fabricated from Modified Sodium Alginate and Gelatin as a Bacterial Barrier

Self‐healing hydrogels as wound dressings still face challenges in infection prevention, especially in the dressing of mass wounds, due to their inflexibility and the slow formation of the protective film on the wound. Therefore, designing a spray‐filming (rapid‐forming) hydrogel that can serve as a bacterial barrier is of particular significance in the development of wound dressings. Here, a self‐healing hydrogel based on adipic acid dihydrazide‐modified gelatin (Gel‐ADH) and monoaldehyde‐modified sodium alginate(SA‐mCHO) is prepared. Using dynamic, Schiff base bonds, the hydrogels exhibit excellent self‐healing properties. Moreover, the gelation time of SA‐mCHO/Gel‐ADH (SG) hydrogels is shortened to 2–21 s, resulting in rapid filming by spraying the two precursor solutions. In addition, the rapid spray‐filming ability might offer sufficient flexibility and rapidity for dealing with mass and irregular wounds. Notably, the bacterial barrier experiments show that the SG hydrogel films could form an effective barrier to Staphylococcus aureus and Candida albicans for 12 h. Therefore, SG hydrogels could be used in wound dressings and they show great promise in applications associated with mass and irregular traumas.     

Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca²⁺, and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.     

Engineering quaternized chitosan in the 3D bacterial cellulose structure for antibacterial wound dressings

Balancing antibacterial properties with biocompatibility is of paramount importance for wound dressings loaded with antibacterial agents. In this work, a water soluble antibacterial agent, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) with an appropriate degree of substitution was introduced into the bacterial cellulose (BC) network by adding it into the BC culture medium. Results indicated that the addition of HACC could affect the yield of BC, porous structure, thermal stability, water absorption and antibacterial properties. HBC-1 with a low content of HACC (13.65 ± 0.30%) cannot inhibit the biofilm formation of bacteria, while HBC-3 with a high content of HACC (62.05 ± 0.90%) has a low yield of BC and confused structure. HBC-2 with an optimum concentration of HACC (37.33 ± 0.80%) possessed a typical porous structure, acceptable thermal stability, good water absorption and favorable antibacterial properties against Staphylococcus aureus (S. aureus, ATCC 25923) and methicillin-resistant S. aureus (ATCC 43300). Most importantly, none of the HACC/BC films exhibited cytotoxicity to NIH3T3 cells. We believe that obtained HACC/BC films with favorable bactericidal properties and biocompatibility could be potential candidates for wound dressings in clinical applications.     

Injectable and self-healing hydrogels with tissue adhesiveness and antibacterial activity as wound dressings for infected wound healing

The design of wound dressings with excellent self-healing ability, adequate adhesion, good biocompatibility, and potential antibacterial ability is of great significance for the healing of infected wounds arising from human activities. Herein, a series of multi-functional hydrogel dressings, poly(ionized isocyanoethyl methacrylate-glutamine)/poly(hexamethylene guanidine) (iG_x/PHMG_y) hydrogels, were obtained through homopolymerization of fully ionized isocyanoethyl methacrylate-glutamine (iIEM-Gln) in the presence of poly(hexamethylene guanidine) (PHMG), in which strong hydrogen bonds were formed among urea groups in the P (iIEM-Gln) chain to form a stable hydrogel network. The prepared iG_x/PHMG_y hydrogels exhibited adequate self-healing ability and tissue adhesion, which could be firmly adhered to the wound surface and remained intact during application. In addition, the presence of PHMG imparted good antibacterial activity to the hydrogels for the effective promotion of the wound healing in S. aureus infected skin wound on mice. Overall, this multi-functional hydrogel provides a facile and effective strategy for the design of infected wound dressings, and may show great potential in clinical applications.     

Multifunctional fibrous wound dressings for refractory wound healing

Refractory wounds have always been an important issue to healthcare systems, whose healing process is always delayed by multiple factors, including bacterial infections, chronic inflammation, and excessive exudates, etc. Employing multifunctional wound dressings is recognized as an effective strategy to deal with refractory wounds, which has yielded promising outcomes in recent years. Among these advanced wound dressings, fibrous dressings have gained growing attention due to their unique merits. Such wound dressings have demonstrated great potential in delivering theranostic agents, such as antibacterial agents, anti-inflammatory drugs, growth factors, and diagnostic probes, etc., for the purposes of accelerating wound healing. This paper reviews the development of multifunctional fibrous dressings and their applications in treating refractory wounds. The construction approaches of novel fibrous dressing with capabilities of antibacterial, anti-inflammation, exudate management and diagnosis were also introduced. Furthermore, the existing problems and challenges are also discussed briefly.     

Hyaluronic acid-methacrylic anhydride/polyhexamethylene biguanide hybrid hydrogel with antibacterial and proangiogenic functions for diabetic wound repair

Diabetic wounds lead to a decrease in quality of life and an increase in mortality. Current treatment strategies include preventing bacterial adhesion while improving microcirculation. As a new type of wound dressing that imitates natural skin, hydrogel has gradually emerged with its excellent properties. However, existing hydrogels rarely achieve satisfactory results in promoting wound repair and antibacterial simultaneously. In this case, we prepared methacrylic anhydride chemically modified hyaluronic acid as a hydrogel matrix, added polyhexamethylene biguanide as an antibacterial component, and loaded sodium alginate/salidroside composite microspheres which could sustainably release salidroside and thus promote angiogenesis. Hybrid hydrogel (HAMA/PHMB-Ms) was synthesized via photocrosslinking, and its chemical structure, particle size distribution and microstructure were characterized. The satisfactory antibacterial properties of the HAMA/PHMB(15%)-Ms hydrogel were studied in vitro, and its antibacterial rates against E. coli and S. aureus were 97.85% and 98.56%, respectively. In addition, after demonstrating its good biocompatibility, we verified that the HAMA/PHMB-Ms hydrogel has increased granulation tissue formation, more collagen deposition, more subcutaneous capillary formation, and better wound healing than blank control, HAMA and HAMA/PHMB hydrogel on the back wound model of diabetic mice. The results confirmed that HAMA/PHMB-Ms hydrogel was a promising material for the treatment of the diabetic wounds.     

On‐Demand Dissolution of a Dendritic Hydrogel‐based Dressing for Second‐Degree Burn Wounds through Thiol–Thioester Exchange Reaction

An adhesive yet easily removable burn wound dressing represents a breakthrough in second‐degree burn wound care. Current second‐degree burn wound dressings absorb wound exudate, reduce bacterial infections, and maintain a moist environment for healing, but are surgically or mechanically debrided from the wound, causing additional trauma to the newly formed tissues. We have developed an on‐demand dissolvable dendritic thioester hydrogel burn dressing for second‐degree burn care. The hydrogel is composed of a lysine‐based dendron and a PEG‐based crosslinker, which are synthesized in high yields. The hydrogel burn dressing covers the wound and acts as a barrier to bacterial infection in an in vivo second‐degree burn wound model. A unique feature of the hydrogel is its capability to be dissolved on‐demand, via a thiol–thioester exchange reaction, allowing for a facile burn dressing removal.     

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

Improvement of dermal burn healing by combining sodium alginate/chitosan-based films and low level laser therapy

This paper aimed to evaluate the improvement of burn wounds healing by sodium alginate/chitosan-based films and laser therapy. Natural polymers with different biological activities are widely used as film dressings to improve wound healing. Lasers arrays accelerate the healing repair of soft tissue injuries. Burn procedures were performed on the backs of 60 male rats assigned into six groups: untreated (CTR), dressed with cellulose films (CL), dressed with sodium alginate/chitosan-based films (SC), laser-irradiated undressed wounds (LT), laser-irradiated wounds with cellulose (CLLT) and sodium alginate/chitosan-based films (SCLT). Laser therapy was applied for 7 days. Animals of each group were euthanised 8 and 14 days after the burn procedures. The inflammatory reaction was significantly more intense in the CTR group than in the irradiated groups after 8 and 14 days. Laser therapy stimulated myofibroblastic differentiation in 8 days, with or without dressing films. Combined laser therapy and both dressings improved epithelisation, blood vessels formation and collagenization, promoted rapid replacement of type III for type I collagen and favored the better arrangement of the newly formed collagen fibres. The combination of laser therapy and sodium alginate/chitosan-based dressing improves burn healing, apparently by modulating the epithelisation, blood vessels formation and collagenization processes.     

Hemocompatibility of Ca2+‐Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis

The present work investigates Ca²⁺‐crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood‐derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet‐free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.     

Antibacterial,Adhesive, and Conductive Hydrogel for Diabetic Wound Healing

Diabetic mellitus is one of the leading causes of chronic wounds and remains a challenging issue to be resolved. Herein, a hydrogel with conformal tissue adhesivity, skin-like conductivity, robust mechanical characteristics, as well as active antibacterial function is developed. In this hydrogel, silver nanoparticles decorated polypyrrole nanotubes (AgPPy) and cobalt ions (Co²⁺) are introduced into an in situ polymerized poly(acrylic acid) (PAA) and branched poly(ethylenimine) (PEI) network (PPCA hydrogel). The PPCA hydrogel provides active antibacterial function through synergic effects from protonated PEI and AgPPy nanotubes, with a tissue-like mechanical property (≈16.8 ± 4.5 kPa) and skin-like electrical conductivity (≈0.048 S m⁻¹). The tensile and shear adhesive strength (≈15.88 and ≈12.76 kPa, respectively) of the PPCA hydrogel is about two- to threefold better than that of fibrin glue. In vitro studies show the PPCA hydrogel is highly effective against both gram-positive and gram-negative bacteria. In vivo results demonstrate that the PPCA hydrogel promotes diabetic wounds with accelerated healing, with notable inflammatory reduction and prominent angiogenesis regeneration. These results suggest the PPCA hydrogel provide a promising approach to promote diabetic wound healing.     

可注射水凝胶在伤口敷料中的研究进展

目前,在伤口治疗中对伤口敷料的选择越来越严格。传统的伤口敷料如纱布、绷带、海绵等在伤口愈合过程中容易诱发细菌感染,延缓伤口愈合,甚至引发慢性并发症。可注射水凝胶具备良好的生物相容性,能够适应伤口的形状以填充伤口,且具备一定的抗菌活性,从而避免伤口感染,相比传统的水凝胶伤口敷料更具备医疗优势,因此在生物医药领域得到广泛关注。本文对天然型可注射水凝胶和复合型可注射水凝胶在伤口愈合中的研究进展进行了综述;也对可注射水凝胶的未来发展趋势进行了展望。     

Development of Gelatin‐Alginate Hydrogels for Burn Wound Treatment

Hydrogels are interesting as wound dressing for burn wounds to maintain a moist environment. Especially gelatin and alginate based wound dressings show strong potential. Both polymers are modified by introducing photocrosslinkable functionalities and combined to hydrogel films (gel‐MA/alg‐MA). In one protocol gel‐MA films are incubated in alg‐MA solutions and crosslinked afterward into double networks. Another protocol involves blending both and subsequent photocrosslinking. The introduction of alginate into the gelatin matrix results in phase separation with polysaccharide microdomains in a protein matrix. Addition of alg(‐MA) to gel‐MA leads to an increased swelling compared to 100% gelatin and similar to the commercial Aquacel Ag dressing. In vitro tests show better cell adhesion for films which have a lower alginate content and also have superior mechanical properties. The hydrogel dressings exhibit good biocompatibility with adaptable cell attachment properties. An adequate gelatin‐alginate ratio should allow application of the materials as wound dressings for several days without tissue ingrowth.     

Preparation of Multi-Functional Quaternary Ammonium Chitosan/Surfactin Hydrogel and its Application in Wound Management

Hydrogel with a 3D network structure can cover the wound to stop the bleeding and support the host tissue infiltration and integration. In this study, an antibacterial hydrogel with hemostasis and the ability to promote wound healing is proposed. This hydrogel comprised surfactin, polyvinylpyrrolidone, and methacrylic anhydride (MA) grafted quaternary ammonium chitosan (CS-MA). The hydrogel formation is triggered by the ultraviolet-initiated polymerization of CS-MA, while the surfactin is complexed with the hydrogel through hydrogen bonding interaction. The results showed that this hydrogel is an adhesive hydrogel with shape adaptability, which can cover the wound surface and promote contact between the hydrogel and the wound surface. More importantly, this hydrogel can simulate the microenvironment of the primary extracellular matrix and increase collagen deposition, and inflammatory factor transformation. The designing of such a multi-functional hydrogel is expected to provide a novel approach to promoting the healing of wounds.     

A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages

Wound dressings have experienced continuous and significant changes since the ancient times. The development starts with the use of natural materials to simply cover the wounds to the materials of the present time that could be specially made to exhibit various extraordinary functions. The modern bandage materials made of electrospun biopolymers contain various active compounds that are beneficial to the healing of wounds. These materials are fibrous in nature, with the size of fibers segments ranging from tens of nanometers to micrometers. With the right choices of biopolymers used for these fibrous materials, they could enhance the healing of wounds significantly compared with the conventional fibrous dressing materials, such as gauze. These bandages could be made such that they contain bioactive ingredients, such as antimicrobial, antibacterial, and anti‐inflammatory agents, which could be released to the wounds enhancing their healing. In an active wound dressing (AWD), the main purpose is to control the biochemical states of a wound in order to aid its healing process. This review provides an overview of different types of wounds, effective parameters in wound healing and different types of wound dressing materials with a special emphasis paid to those prepared by electrospinning. Copyright © 2009 John Wiley & Sons, Ltd.     

Impact of polymeric films and hydrogels: Physical characteristics on bacterial growth

Hydrogels find diverse applications in manipulating bacteria, and serving purposes like elevation, maintenance, and elimination. Several factors of hydrogel have been studied in the benefits of antibacterial activity. Factors such as hydrogel stiffness and roughness gain significance in surface coating, influencing bacterial behavior. However, the intricate interplay of hydrogel stiffness, roughness, polymer types, and bacterial species necessitates further exploration. The choice of polymer is dictated by the specific objectives, particularly in antibacterial scenarios where polymers with positive charge, hydrophilicity, and acidity prove effective. These properties induce robust electrostatic and hydrophobic/hydrophilic interactions, along with pH-induced cell membrane damage, collectively contributing to hindered bacterial adhesion and growth. Additionally, extracellular polymeric substances (EPS) emerge as pivotal influencers in bacterial adhesion and proliferation. EPS production alters bacterial surfaces, fostering connections between bacteria and facilitating biofilm formation. The hydrophobic nature of EPS further complicates bacterial interactions with surface materials, emphasizing the nuanced interplay of hydrophilic and hydrophobic forces in bacterial adhesion. Herein, this work article has reviewed the related study of each physical property related to antibacterial property on the surface of the hydrogel. Moreover, this work also illustrates applications of the antibacterial properties of hydrogel for medical and surface treatment, including wound healing, food packaging, and surface coating. Additionally, the bacteria growing on hydrogel for engineered living materials, have been updated in various applications.     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

A Hydrogel‐Based Localized Release of Colistin for Antimicrobial Treatment of Burn Wound Infection

There is an urgent unmet medical need for new treatments for wound and burn infections caused by multidrug‐resistant Gram‐negative “superbugs,” especially the problematic Pseudomonas aeruginosa . In this work, the incorporation of colistin, a potent lipopeptide into a self‐healable hydrogel (via dynamic imine bond formation) following the chemical reaction between the amine groups present in glycol chitosan and an aldehyde‐modified poly(ethylene glycol), is reported. The storage module (G ′) of the colistin‐loaded hydrogel ranges from 1.3 to 5.3 kPa by varying the amount of the cross‐linker and colistin loading providing different options for topical wound healing. The majority of the colistin is released from the hydrogel within 24 h and remains active as demonstrated by both antibacterial in vitro disk diffusion and time‐kill assays. Moreover and pleasingly, the colistin‐loaded hydrogel performs almost equally well as native colistin against both the colistin‐sensitive and also colistin‐resistant P. aeruginosa strain in the in vivo animal “burn” infection model despite exhibiting a slower killing profile in vitro. Based on this antibiotic performance along with the biodegradability of the product, it is believed the colistin‐loaded hydrogel to be a potential localized wound‐healing formulation to treat burn wounds against microbial infection.

     

Positively and negatively charged ionic modifications to cellulose assessed as cotton-based protease-lowering and hemostatic wound agents

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapping but distinct phases of wound healing wherein different dressing material properties are required to bring pathological events under control when they present as a result of trauma or chronic wounds. Thus, we have designed cellulose wound dressings with properties that function through modified fiber surface properties to lower protease levels in the chronic wound and promote clotting in hemorrhaging wounds. With this in mind three finishing chemistries utilizing traditional pad-dry-cure approaches were explored for their potential to confer charged properties to cotton dressings. Cellulose dressings designed to remove cationic serine proteases from highly exudative chronic wounds were created to present negatively charged fibers as an ion exchange mechanism of protease-lowering. Phosphorylated cotton and polycarboxylic acid crosslinked cotton were prepared to examine their ability to remove human neutrophil elastase (HNE) from surrogate wound fluid. A cellulose phosphorylation reaction utilizing sodium hexametaphosphate: urea was explored to optimize cellulose phosphorylation as a function of HNE sequestration efficacy. Acid catalyzed cross linking of cellulose with butane-tetracarboxylic acid also resulted in a negatively charged dressing that removed HNE from solution more effectively than phosphorylated cellulose. Collagenase sequestration was also assessed with phosphorylated cellulose and polycarboxylic acid cross linked cellulose derivatives. Butanetetracarboxylic acid and phosphorylated cellulose functioned to remove collagenase from solution most effectively. Cellulose dressings designed to accelerate thrombosis and aggregation of blood platelets were prepared with a view to examining derivatized cotton fibers bearing a net positive charge to promote hemostasis. Cellulose and chitosan dressings bearing an aminoglucan functionality were created by grafting chitosan on cotton and preparing aminized cotton. The preparation of chitosan-grafted cotton dressings was completed with a citric acid grafting onto cellulose. Aminized cotton was functionalized as an ethylamino-ether cellulose derivative. The chitosan-grafted and aminized cotton demonstrated a dose response gelling of citrated sheep blood.     

Protease and ROS activities influenced by a composite of bacterial cellulose and collagen type I <Emphasis Type="Italic">in vitro</Emphasis>

The application of bacterial cellulose as a dressing for chronic and burn wounds has been described as beneficial for healing. However, this study and other tests have shown that bacterial cellulose has no significant influence on the biochemical state of chronic wounds. Such wounds persist in the inflammatory phase of the normal healing process and fail to heal. Exudates from non-healing wounds show elevated levels of proteolytic enzymes, cytokines and reactive oxygen species (ROS), leading to a reduced concentration of growth factors and proteinase inhibitors and to a degradation of tissue and severe damage. Thus, the reduction of protein degrading enzymes and proinflammatory interleukins as well as scavenging of ROS appears to be a suitable way to support the healing process. The aim of the present study was to improve the positive features of bacterial cellulose as wound dressing by incorporation of collagen type I into the cellulose pellicle. The research focussed on the possible in situ formation of a composite of bacterial cellulose and collagen type I. This biomaterial is able to reduce the amount of selected proteases and interleukins significantly and possesses a distinct antioxidant capacity as well.