A comprehensive review of the polymer-based hydrogels with electrochemically synthesized silver nanoparticles for wound dressing applications

Modernization and improvement of wound dressing materials is an important topic in biomaterials and biomedicine fields, as the traditional materials are inadequate and susceptible to bacterial infections. In recent times, polymer-based hydrogel materials have presented themselves as excellent candidates for new-generation wound dressings with improved properties, such as high sorption ability, good mechanical properties, and low adhesiveness. Additionally, cross linked hydrogel matrices serve as excellent carriers for controlled release of antibacterial agents, such as silver nanoparticles (AgNPs), which are preferred over conventional antibiotics due to multi-phase mechanism of action and low susceptibility to induce bacterial resistance. Their incorporation inside polymer matrices allows improvement of wound dressing properties and sustained protection against bacterial infection. Electrochemical methods for AgNPs synthesis are facile and green alternatives to chemical routes, allowing the formation of highly stable AgNPs with strong antibacterial effect. In this article, we aim to provide a comprehensive review of the existing research on the topic of electrochemically synthesized silver nanoparticles incorporated in polymer matrices with a special focus on the chitosan-based hydrogels as prospective materials for wound dressing applications.     

Development of Novel Green Synthesized Silver Nanoparticles with Superior Antibacterial and Wound Healing Properties in Nursing Care After Rectal Surgery

The present investigation showed the green synthesis of silver nanoparticles (AgNPs) using Ficus benghalensis (F. benghalensis) leaf extract. UV–Vis spectra of the biofabricated AgNPs displayed its maximum peak of absorption at 461 nm. High resolution-transmission electron microscopy images displayed the shape of AgNPs as spherical with an average diameter of 35 nm size. The analysis of X-ray diffraction confirmed the presence of crystalline AgNPs. The analysis of Fourier-transform infrared spectroscopy confirmed the existence of bioconstituents such as terpenoids, phenolics and flavonoids, which functions as bio-reducing agents. When compared with F. benghalensis extract, AgNPs displayed the considerably greater bioactivities. The exceptional antimicrobial functionalities of AgNPs against both the gram positive and gram negative bacteria makes them appropriate candidates for the production of antibiotics against the species that are resistant to traditional antibiotics. The assay of HDFa cell scratch confirmed that the AgNPs have greater ability of wound healing than the leaf extract of F. benghalensis. Altogether, the obtained results showed the application of synthesized AgNPs in the production of novel drugs that are used for wound healing in nursing care after rectal surgery.

     

Rational Design of Ag/ZnO Hybrid Nanoparticles on Sericin/Agarose Composite Film for Enhanced Antimicrobial Applications

Silver-based hybrid nanomaterials are receiving increasing attention as potential alternatives for traditional antimicrobial agents. Here, we proposed a simple and eco-friendly strategy to efficiently assemble zinc oxide nanoparticles (ZnO) and silver nanoparticles (AgNPs) on sericin-agarose composite film to impart superior antimicrobial activity. Based on a layer-by-layer self-assembly strategy, AgNPs and ZnO were immobilized on sericin-agarose films using the adhesion property of polydopamine. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray powder diffraction spectroscopy were used to show the morphology of AgNPs and ZnO on the surface of the composite film and analyze the composition and structure of AgNPs and ZnO, respectively. Water contact angle, swelling ratio, and mechanical property were determined to characterize the hydrophilicity, water absorption ability, and mechanical properties of the composite films. In addition, the antibacterial activity of the composite film was evaluated against Gram-positive and Gram-negative bacteria. The results showed that the composite film not only has desirable hydrophilicity, high water absorption ability, and favorable mechanical properties but also exhibits excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria. It has shown great potential as a novel antimicrobial biomaterial for wound dressing, artificial skin, and tissue engineering.     

Aminoglycoside hydrogels based on dynamic covalent bonds with pH sensitivity,biocompatibility, self-healing,and antibacterial ability

Despite aminoglycosides (AGs) have superior antibacterial ability, all approved AGs by FDA are associated with adverse effects such as ototoxicity and nephrotoxicity. To solve these problems, AGs hydrogels based on dynamic covalent bond cross-linking were quickly prepared within 25 s by using AGs, aldehyde hyaluronic acid (A-HA), and adipic acid dihydrazide graft hyaluronic acid (HA-ADH) as materials. FT-IR, thermal analysis, and SEM results exhibited that A-HA/HA-ADH/AGs hydrogels were successfully synthesized with highly porous and interconnected network structure. The water absorption ratio of the hydrogels increased with the decreasing pH and temperature, indicating the hydrogels were pH- and temp-responsive. The pH-dependent degradation also demonstrated pH sensitivity of the hydrogels. Rheology and self-healing analysis assessment displayed that AGs hydrogels had good mechanical property, self-healing ability, and injectability. The hydrogels had no cytotoxicity to L929 cells and their hemolysis ratios were between 0.7% and 1.3%, which reached a nontoxic level. Most importantly, inhibition zones results demonstrated that the hydrogels had excellent and sustained antibacterial performance against Escherichia coli and Staphylococcus aureus. Therefore, A-HA/HA-ADH/AGs hydrogels are potential dressings for wound healing. Further plans including antibacterial and in vivo wound healing assays will be shown in the next work.     

Advances in Nanotechnology towards Development of Silver Nanoparticle-Based Wound-Healing Agents

Since antiquity, silver-based therapies have been used in wound healing, wound care and management of infections to provide adequate healing. These therapies are associated with certain limitations, such as toxicity, skin discolouration and bacterial resistance, which have limited their use. As a result, new and innovative wound therapies, or strategies to improve the existing therapies, are sought after. Silver nanoparticles (AgNPs) have shown the potential to circumvent the limitations associated with conventional silver-based therapies as described above. AgNPs are effective against a broad spectrum of microorganisms and are less toxic, effective at lower concentrations and produce no skin discolouration. Furthermore, AgNPs can be decorated or coupled with other healing-promoting materials to provide optimum healing. This review details the history and impact of silver-based therapies leading up to AgNPs and AgNP-based nanoformulations in wound healing. It also highlights the properties of AgNPs that aid in wound healing and that make them superior to conventional silver-based wound treatment therapies.     

State of arts on the bio-synthesis of noble metal nanoparticles and their biological application

Nanomaterials are materials in which at least one of the dimensions of the particles is 100 nm and below. There are many types of nanomaterials, but noble metal nanoparticles are of interest due to their uniquely large surface-to-volume ratio, high surface area, optical and electronic properties, high stability, easy synthesis, and tunable surface functionalization. More importantly, noble metal nanoparticles are known to have excellent compatibility with bio-materials, which is why they are widely used in biological applications. The synthesis method of noble metal nanoparticles conventionally involves the reduction of the noble metal salt precursor by toxic reaction agents such as NaBH₄, hydrazine, and formaldehyde. This is a major drawback for researchers involved in biological application researches. Hence, the bio-synthesis of noble metal nanoparticles (NPs) by bio-materials via bio-reduction provides an alternative method to synthesize noble metal nanoparticles which are potentially non-toxic and safer for biological application. In this review, the bio-synthesis of noble metal nanoparticle including gold nanoparticle (AuNPs), silver nanoparticle (AgNPs), platinum nanoparticle (PtNPs), and palladium nanoparticle (PdNPs) are first discussed. This is followed by a discussion of these biosynthesized noble metal in biological applications including antimicrobial, wound healing, anticancer drug, and bioimaging. Based on these, it can be concluded that the study on bio-synthesized noble metal nanoparticles will expand further involving bio-reduction by unexplored bio-materials. However, many questions remain on the feasibility of bio-synthesized noble metal nanoparticles to replace existing methods on various biological applications. Nevertheless, the current development of the biological application by bio-synthesized noble metal NPs is still intensively ongoing, and will eventually reach the goal of full commercialization.     

Silver Nanoparticles Mediate Differential Responses in Keratinocytes and Fibroblasts during Skin Wound Healing

With advances in nanotechnology, pure silver has been recently engineered into nanometer‐sized particles (diameter <100 nm) for use in the treatment of wounds. In conjunction with other studies, we previously demonstrated that the topical application of silver nanoparticles (AgNPs) can promote wound healing through the modulation of cytokines. Nonetheless, the question as to whether AgNPs can affect various skin cell types—keratinocytes and fibroblasts—during the wound‐healing process still remains. Therefore, the aim of this study was to focus on the cellular response and events of dermal contraction and epidermal re‐epithelialization during wound healing under the influence of AgNPs; for this we used a full‐thickness excisional wound model in mice. The wounds were treated with either AgNPs or control with silver sulfadiazine, and the proliferation and biological events of keratinocytes and fibroblasts during healing were studied. Our results confirm that AgNPs can increase the rate of wound closure. On one hand, this was achieved through the promotion of proliferation and migration of keratinocytes. On the other hand, AgNPs can drive the differentiation of fibroblasts into myofibroblasts, thereby promoting wound contraction. These findings further extend our current knowledge of AgNPs in biological and cellular events and also have significant implications for the treatment of wounds in the clinical setting.     

Construction of chitosan-carboxymethyl β-cyclodextrin silver nanocomposite hydrogel to improve antibacterial activity

Silver nanoparticles (AgNPs) are widely used in various fields but their physical and chemical instability have limited their applications. The present work demonstrates a novel approach for the synthesis and stabilising of AgNPs. Chitosan and carboxymethyl β-cyclodextrin were used to prepare a polymeric hydrogel with glutaraldehyde as cross-linker. As a result, AgNPs were formed with very high dispersion and stability in the hydrogel structure. It is possible to create nanoreactors to produce AgNPs by adding CM-βCD to the structure of the hydrogel. Fourier transform infrared (FTIR) analysis was employed to characterise the Cs-CM-βCD hydrogel. The morphologies of pure Cs-CM-βCD hydrogel and silver nanocomposite were observed by scanning electron microscopy. Moreover, UV–VIS spectroscopy and X-ray diffraction were used to characterise the prepared silver nanocomposite. In addition, the antibacterial properties of these silver nanocomposite hydrogels were investigated against Staphylococcus aureus (Gram positive) and Escherichia coli (Gram negative).     

Ultrasmall silver nanoparticles loaded in alginate–hyaluronic acid hybrid hydrogels for treating infected wounds

Nowadays, silver nanoparticles are in the limelight to control infection during wound healing process, and a vast variety of antimicrobial dressings based on colloidal silver have been marketed to fight wound invasion of pathogen bacteria, which represents one of the main adverse effects limiting the repair process. Here we propose a biofunctional hydrogel based on alginate (ALG) and hyaluronic acid (HA) embedding ultrasmall silver nanoparticles (usSN, <1?nm) as antimicrobial component. The hydrogels were fabricated in different size by a straightforward internal gelation method using CaCO₃ and glucono-δ-lactone. To follow usSN release from the hydrogels in aqueous media, catalytic activity of usSN-loaded hydrogels was evaluated. Results suggested that catalytic activity was low in intact hydrogels and high when hydrogels dissolved, which suggests that usSN firmly interact with polymer chains and are available in the medium depending on the extent of hydrogel degradation. HA-containing hydrogels showed faster dissolution in simulated physiological conditions and higher antibiofouling properties as compared to hydrogels made only of ALG. Free usSN were not toxic toward human mesenchymal stem cells (Ad-MSCs), previously isolated from subcutaneous adipose tissue biopsies, up to 50?µg/mL. At this concentration, viability of Ad-MSCs was unaffected whereas their motility was significantly higher as compared to control (p<0.01) for both free usSN and hydrogel integrating. Antimicrobial activity on clinical isolates of both Gram-positive and Gram-negative bacteria demonstrated that usSN at 50?µg/mL were able to kill all the bacteria tested after 24 and 48?h of contact time. In the case of hydrogels, a matrix effect was found and bacterial killing was significant only at 24?h and dependent on bacterial strain, being Gram-negative bacteria more susceptible. These results clearly indicate that usSN interaction with polymer network and exposure time can strongly affect usSN antimicrobial profile in the hydrogel and, in turn, timing of hydrogel change at injured site in a clinical setting. On the whole, ALG/HA hydrogels integrating usSN can be considered a suitable option to fabricate biofunctional dressings for hospitalized patients and worth of further in vivo investigation.     

Nontoxic pH-sensitive silver nanocomposite hydrogels for potential wound healing applications

ABSTRACT

Silver nanocomposite (SNC) containing pH sensitivity with fascinating attention may be recommended for extensive utilization in eco-friendly nanomaterial applications. In the present investigation, a strategy to fabricate new biodegradable and biocompatible hydrogels based on sodium alginate/ethylene glycol/acrylic acid functionalized with silver nanocomposites, which were synthesized by a facile greener method. The swelling profile is enhanced the stimuli responsive behavior of nanocomposite hydrogels. The synthesized nanocomposite hydrogels has showed a significant pH-sensitive behavior which induced the degradation profile, cell viability, and antimicrobial activity. Hence, this kind of biomaterials has been utilized for nontoxic, degradable wound healing dressing.     

Polyvinyl-Pyrrolidone-Coated Silver Nanoparticles—The Colloidal,Chemical, and Biological Consequences of Steric Stabilization under Biorelevant Conditions

(1) Background: Several properties of silver nanoparticles (AgNPs), such as cytotoxic, anticancer, and antimicrobial activities, have been subjects of intense research; however, important aspects such as nanoparticle aggregation are generally neglected, although a decline in colloidal stability leads to a loss of the desired biological activities. Colloidal stability is affected by pH, ionic strength, or a plethora of biomolecules that interact with AgNPs under biorelevant conditions. (2) Methods: As only a few studies have focused on the relationship between aggregation behavior and the biological properties of AgNPs, here, we have systematically evaluated this issue by completing a thorough analysis of sterically (via polyvinyl-pyrrolidone (PVP)) stabilized AgNPs that were subjected to different circumstances. We assessed ultraviolet–visible light absorption, dynamic light scattering, zeta potential measurements, in vitro cell viability, and microdilution assays to screen both colloidal stability as well as bioactivity. (3) Results: The results revealed that although PVP provided outstanding biorelevant colloidal stability, the chemical stability of AgNPs could not be maintained completely with this capping material. (4) Conclusion: These unexpected findings led to the realization that stabilizing materials have more profound importance in association with biorelevant applications of nanomaterials than just being simple colloidal stabilizers.     

In vitro and in vivo investigational studies of a nanocomposite‐hydrogel‐based dressing with a silver‐coated chitosan wafer for full‐thickness skin wounds

A nanocomposite reservoir‐type hydrogel dressing of poly vinyl alcohol (PVA) was fabricated by a freeze–thaw method and loaded with silver‐nanoparticle‐coated chitosan wafers (Ag–CHWs). The Ag–CHWs were synthesized by a sonication technique with silver nitrate (AgNO₃) and chitosan powder. Scanning electron microscopy images showed silver nanoparticles (AgNPs) with a size range of 10 ± 4 nm on the surface of the chitosan wafers, and the antibacterial efficacy (minimum inhibitory concentration) of the Ag–CHWs was measured against Pseudomonas aeruginosa (32 µg/mL), Staphylococcus aureus, (30 µg/mL) and Escherichia coli (32 µg/mL). The antimicrobial PVA hydrogel showed an improved tensile strength (～0.28 MPa) and gel content (～92%) in comparison with the blank hydrogels. Full‐thickness‐excision wound studies of the nanocomposite dressing on Wistar rats revealed enhanced wound contraction, improved inflammation response, re‐epithelization rate, neoangiogenesis, and granulation tissue formation in comparison to the control group. A flexible, biocompatible, nanocomposite reservoir dressing not only established the chitosan as a stabilizer but also proved the efficacious and safe utility of AgNPs toward chronic wound management. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43472.     

A Facile Strategy for Preparing Tough,Self‐Healing Double‐Network Hyaluronic Acid Hydrogels Inspired by Mussel Cuticles

Compared with hydrogel‐like biological tissues such as cartilage, muscles, and blood vessels, current hyaluronic acid hydrogels often suffer from poor toughness and limited self‐healing properties. Herein, a facile and generalizable strategy inspired by mussel cuticles is presented to fabricate tough and self‐healing double‐network hyaluronic acid hydrogels. These hydrogels are composed of ductile, reversible Fe³⁺‐catechol interaction primary networks, and secondarily formed brittle, irreversible covalent networks. Based on this design strategy, the hyaluronic acid hydrogels are demonstrated to exhibit reinforced mechanical strength while maintaining a rapid self‐healing property. In addition, by simply regulating pH or UV irradiation time, the mechanical properties of the hydrogels can be regulated conveniently through variations between the primary and secondary networks.     

Fabrication of Au and Ag Bi-metallic nanocomposite for antimicrobial applications

Hydrogel silver nanocomposites have shown immense potential in many biomedical applications, specifically wound healing. The combination of bi-metallic (Ag, Au) hydrogel nanocomposites are developed to enhance their antimicrobial activity. This paper presents the fabrication of bi-metallic nanocomposites obtained from the synthesis of acrylamide (AM) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) based hydrogels for antimicrobial applications. The nanocomposite formation was confirmed by scanning electron microscopy (SEM), thermal analysis (TGA/DSC), as well as X-ray diffraction (XRD) methods. The bi-metallic nanocomposite hydrogel has shown significant antibacterial activity on bacillus. Therefore, these bi-metallic antibacterial materials are promising candidates for a wide range of biomedical applications. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Tuning the antimicrobial activity of collagen biomaterials through a liposomal approach

The development of advanced biocidal agents stands as a global challenge, focused on the increasing demand of new biomaterials with local and gradual release of antimicrobial agents. This is the first time that three well-known materials are strategically combined to develop a novel biomaterial with long-term bactericidal activity that avoids burst release and toxic effects, by the incorporation of silver nanoparticles in liposomes and the subsequent incorporation of these assemblies in collagen hydrogels. These systems show improved mechanical properties and prolonged inhibitory effect on the growth of Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria, while remaining highly biocompatible for epithelial cells. In fact, the hybrid biocomposite prevents bacterial colonization for at least 72 h, allowing at the same time eukaryotic cell proliferation. As a result, this new bactericidal biomaterial provides a new alternative to improve current treatments of bacterial infections with many implications in significant applications, such as wound therapy and tissue regeneration.     

pHEMA: An Overview for Biomedical Applications

Poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial with excellent biocompatibility and cytocompatibility elicits a minimal immunological response from host tissue making it desirable for different biomedical applications. This article seeks to provide an in-depth overview of the properties and biomedical applications of pHEMA for bone tissue regeneration, wound healing, cancer therapy (stimuli and non-stimuli responsive systems), and ophthalmic applications (contact lenses and ocular drug delivery). As this polymer has been widely applied in ophthalmic applications, a specific consideration has been devoted to this field. Pure pHEMA does not possess antimicrobial properties and the site where the biomedical device is employed may be susceptible to microbial infections. Therefore, antimicrobial strategies such as the use of silver nanoparticles, antibiotics, and antimicrobial agents can be utilized to protect against infections. Therefore, the antimicrobial strategies besides the drug delivery applications of pHEMA were covered. With continuous research and advancement in science and technology, the outlook of pHEMA is promising as it will most certainly be utilized in more biomedical applications in the near future. The aim of this review was to bring together state-of-the-art research on pHEMA and their applications.     

无患子提取液制备纳米银及其协同抗菌性研究

以无患子提取液为还原剂,制备了含有纳米银的无患子复合抗菌液,考察了无患子提取液用量、温度、硝酸银摩尔浓度等因素对纳米银形貌和粒径的影响,并借助UV-Vis可见分光光谱、X射线衍射(XRD)以及透射电子显微镜(TEM)对产物进行表征;通过抑菌环法探讨了复合抗菌液对大肠杆菌的抗菌活性。由UV-Vis图谱可知,复合抗菌液等离子体共振吸收峰(SPR)在418 nm左右,说明该复合抗菌液中有纳米银的存在;XRD图表明合成的纳米银为面心立方结构;TEM图表明合成纳米银粒径为10~40 nm。由此获得的含有纳米银的无患子复合抗菌液对大肠杆菌表现出显著协同抗菌活性,抑菌圈直径变大。     

Topical delivery of silver nanoparticles promotes wound healing

Wound healing is a complex process and has been the subject of intense research for a long time. The recent emergence of nanotechnology has provided a new therapeutic modality in silver nanoparticles for use in burn wounds. Nonetheless, the beneficial effects of silver nanoparticles on wound healing remain unknown. We investigated the wound-healing properties of silver nanoparticles in an animal model and found that rapid healing and improved cosmetic appearance occur in a dose-dependent manner. Furthermore, through quantitative PCR, immunohistochemistry, and proteomic studies, we showed that silver nanoparticles exert positive effects through their antimicrobial properties, reduction in wound inflammation, and modulation of fibrogenic cytokines. These results have given insight into the actions of silver and have provided a novel therapeutic direction for wound treatment in clinical practice.     

Advances in wound dressing based on electrospinning nanofibers

In recent years, there has been a significant focus on bioactive dressings suitable for treating chronic and acute wounds. Electrospinning nanofibers are considered advanced dressing options due to their high porosity and permeability to air and water, effective barrier properties against external pathogens, and excellent resemblance to the extracellular matrix for wound healing and skin regeneration. This article reviews the recent advancements in the application of electrospinning nanofibers for bioactive wound healing. The review begins with an overview of the wound healing process and electrospinning methods. It then explores the advantages and disadvantages of different synthetic and natural polymers used in the preparation of electrospinning wound dressings. The natural polymers discussed in this review include collagen, gelatin, silk fibroin, chitosan, hyaluronic acid, and sodium alginate. Additionally, the review delves into commonly used synthetic polymers like polyvinyl alcohol, polyvinyl chloride, polyethylene lactone, polylactide, and polyurethane for wound dressing applications. Furthermore, the review examines the blending of natural and synthetic polymers to create high-performance wound dressings. It also explores the incorporation of functional additives, such as antimicrobial agents, growth factors, and natural extracts, into electrospinning nanofibers to expedite wound healing and tissue repair. In conclusion, electrospinning is an emerging technology that provides unique opportunities for designing more effective wound dressings and care products.     

Physicochemical and antimicrobial properties of sodium alginate/gelatin-based silver nanoformulations

In the present investigation, synthesis of silver nanoparticles (AgNPs) has been successfully carried out in a very simple and cost-effective manner by reducing Ag⁺ ions in sodium alginate solution and further stabilizing the colloidal mixture with gelatin solution. The ultraviolet–visible (UV–vis) spectra were in excellent agreement with the nanostructure morphology obtained from dynamic light scattering transmission electron microscopy and their size distributions. Increase in precursor concentration was found to promote agglomeration of AgNPs. Antibacterial assays revealed that the nanoformulations were more active against Gram-negative bacteria. Swelling studies of the hydrogel films demonstrated a rapid increase in water uptake. However, an increase in swelling % was observed with decreasing AgNP content. The use of biocompatible materials such as sodium alginate and gelatin not only provides green and economic attributes to this piece of research work but, at the same time, also opens up possibilities of using the nanoformulations in wound dressings, active packaging and several other biomedical applications.