Hydrogel ppt.

Hydrogel; Enhancing it's wound-healing properties.

Page

Index

3-4

1. What is hydrogel?

2. Applications of hydrogel

6-7

3. What is a biofilm?

4. Hydrogel as wound dressing

8-10

12-37

5. Articles related to hydrogel preparations

6. Conclusion

38

What is a hydrogel?

Definition of hydrogel:

A hydrogel is a water insoluble three dimensional network of natural or synthetic polymers and a fluid, having absorbed a large amount of water or biological fluids.

Applications of hydrogel:

• Tissue engineering scaffolds
• Disposable diapers
• Biosensors, etc.

• Breast implants
• Contact lenses
• Wound dressings
• Cell culturing

What is a biofilm?

Definition of biofilm:

• Micro-organisms irreversibly attach to and grow on a surface to produce extracellular polymers to enhance attachment and matrix formation.This network structure is called a biofilm.
• It’s a survival strategy used by micro-organisms against antibiotics.
• The major complication encountered during wound healing processes is the formation of biofilms.

Hydrogel as wound dressing:

1. Hydrogels are hydrophilic polymers with very high water content that are meant to hydrate wounds.
2. They are insoluble polymers that expand in water.
3. They provide a moist environment for cell migration and absorb some exudate, thereby promoting healing.
4. Hydrogels have a marked cooling and soothing effect on the skin, which is valuable in healing burns and painful wounds.
5. The cooling effect also offers pain-relief to the patients.

Although hydrogels on their own have various wound healing properties, they are cross linked with a variety of materials to enhance their effect against biofilm formation during wound healing.

Following are the articles related to various hydrogel preparation methods:

Aggregation-Induced Emission-Active Amino acid/Berberine Hydrogels with enhanced Photodynamic Antibacterial and Anti-biofilm Activity:

• A novel hybrid hydrogel was assembled from Fmoc-Phe and berberine chloride (BBR) by aggregation-induced emission behaviour.

• The hydrogel showed enhanced photodynamic antibacterial and anti-biofilm activity.
• The hydrogel facilitated the repair of wounds in rats infected with S. aureus.
• The excellent therapeutic capabilities of the Fmoc-F/BBR hydrogel on wounds infected with S. aureus were demonstrated in vivo.

AgNP/Alginate Nanocomposite hydrogel for antimicrobial and antibiofilm applications:

• The incorporation of thioctic acid-capped AgNPs into an alginate gel matrix through M2+-mediated ionic cross-linking was done.Increase of 47.2% in elastic modulus, 30% in viscosity, and 31.2% in resistance to low shear rates likely due to uniform cross bridging of AgNPs to the alginate monomers through Ca2+ ions and occurred at an optimum concentration of 10-20 μg g-1 crosslinked AgNPs.

• All calcium based alginate gels appeared to form bidentate chelating coordination, suggesting little to no direct interaction of metal ions derived from AgNPs with the guluronic or mannuronic acid groups – whereas Ag- alginate gels demonstrated a strong shift of ν(COO-)sym to a lower wavenumber frequency, attributed to a change in carboxylate metal coordination.

• A MBC of 25 μg g-1 AgNP was determined across the wide range of planktonic microorganisms investigated, and a time dependent kill kinetics were observed over 180 minutes.
• The AgNP alginate gelshowed significant cell killing on biofilms of Gram positive and negative bacteria, which ranged from the lowest effect of killing of 44% for S.aureus, and highest of 61% for E.coli.
• A time-dependent limited release of silver was observed from the AgNP alginate gel through biofilm structures, which is a desirable feature for persistent antimicrobial effects.

Bacteriophage delivering hydrogels reduce biofilm formation in vitro and infection in vivo:

• We engineered an injectable hydrogel capable of encapsulating active bacteriophage and delivering them to the site of bone infections.

• The scaffold was able to deliver live bacteriophage after encapsulation, and significantly reduced the number of live P. aeruginosa bacteria in both planktonic and biofilm phenotypes in vitro.

• Importantly, this bacteriophage-encapsulating hydrogel significantly reduced P. aeruginosa infection in a murine radial defect model while showing similar gross host responses to bacteriophage-free hydrogels.

Biocompatible alginate silica supported silver nanoparticles composite films for wound dressing with antibiofilm activity:

• Silver nanoparticles on silica support were obtained by following a simple and reproducible approach without the use of any solvent and reagent waste.
• The prepared and characterized films showed good hydration properties and a very slow silver ion release.
• Films showed antimicrobial activity limited to the zone of application, maybe due to direct contact action of silver nanoparticles embedded in films, antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa and lack of cytotoxicity for fibroblasts and keratinocytes.

• Films containing silver acetate with the same silver ions concentrations, but lack of silver-silica composites, showed comparable antimicrobial and antibiofilm activities but showed high cytotoxicity.
• This is a remarkable goal as silver nanoparticles are known to possess antimicrobial activity but the high cytotoxicity for the host limits their use.

Chitosan-based hydrogel for the dual delivery of antimicrobial agents against bacterial Methicillin-Resistant Staphylococcus aureus biofilm-infected wounds:

• In this paper, the antibiofilm and wound healing efficacy of hydrogels of natural origin for the codelivery of HP and Ps was explored.
• After successfully preparing the hydrogels via the Michael addition reaction and incorporating into them the antibacterial agents(HP and P), their porous structure were shown to permit a slower release of the incorporated antibacterial agent from the hydrogel matrixwhen compared to the release from the buffer.
• The hydrogel was confirmed to be biosafe/nontoxic and exhibited excellent viscosity appropriate for topical application.
• The in-vitro antibacterial/antibiofilm evaluation of the HP-releasing hydrogels revealed superior antibacterial/antibiofilm efficacy against MRSA compared to HP alone as seen in lower MIC values and a reduced number of bacterial colonies.

• The in-vivo wound-healing studies in the MRSA biofilm-infected mice model showed a more rapid wound closure and reduced bacterial burden in groups exposed to the HP-loaded hydrogels when compared to free HP. These findings were further corroborated by the histomorphological analysis of H&E, PSR, and CAB stained sections of the tissue samples.
• The observed greater antibacterial/biofilm activity of the HP and P co-loaded hydrogel demonstrated a synergetic relationship.

• This implies that the incorporation of the P enhanced the activity of the HP-releasing hydrogel.
• The results of this study suggest that combination therapy may become a better approach for targeting bacterial biofilms.
• Also, the HP-releasing hydrogel may serve as a new delivery system for treating chronic wound infection to achieve rapid healing, thus enhancing the quality of life.

Wound dressings coated with silver nanoparticles and essential oils for the management of wound Infections:

• The potential of silver NPs functionalized with EOs to inhibit microbial colonization and biofilm formation on nanocoated wound dressings was evaluated.
• The use of natural compounds and materials such as alginate and essential oils (mandarin, clove and niaouli) together with silver NPs have permitted the development of improved wound dressings.

• These could be efficiently utilized for the management of wounds, by avoiding infection without the use of antibiotics and antiseptic topic products.

Fabrication of antibacterial sericin based hydrogel as an injectable and mouldable wound dressing:

• In summary, we fabricated a semi-interpenetrating sericin/sodium alginate network hydrogel crosslinked by calcium ions.
• AgNPs were synthesized in situ in the hydrogel by the redox property of tyrosine in

• sericin.
• The hybrid hydrogel has exhibited excellent cytocompatibility, moisture retention property, antibacterial activity and promoting wound healing ability.

• It is promising in antibacterial applications such as wound dressing and skin repairing.

Antibacterial, antibiofilm and cytotoxic activities of biogenic polyvinyl alcohol-silver and chitosan-silver nanocomposites:

• PVA-Ag and CS-Ag nanocomposite films were synthesized by augmentation with biosynthesized AgNPs, using Enterobacter cloacae Ism 26 (KP988024).

• PVA-Ag and CS-Ag nanocomposites showed higher thermal stability than pure PVA and CS films.

• AgNPs showed homogenous dispersion through PVA and CS matrices, preventing the nanoparticles from aggregation.

• These nanocomposite films enhanced significantly the antimicrobial/biofilm activities of AgNPs causing efficient eradication of bacterial and biofilm growth of multi-drug resistant clinical isolates.

• Nanocomposites showed significant low cytotoxicity against Huh-7 liver cells.

• These results highlighted the enhanced biological activities of nanocomposites using biogenically synthesized nanoparticles and biodegradable polymers, helping in the usage of environmentally friendly, nontoxic PVA-Ag and CS-Ag nanocomposite films in many biomedical and industrial applications.

Co-immobilization of cellobiose dehydrogenase and deoxyribonuclease I on chitosan nanoparticles against fungal/bacterial polymicrobial biofilms targeting both biofilm matrix and microorganisms:

• In this study, both CDH and DNase were co-immobilized on positively charged CSNPs to form bi-functional NPs that synergistically target biofilm matrix and microorganisms.
• The positively charged NPs showed spherical shape and narrow size distribution. CSNP-DNase-CDH exhibited excellent inhibition activity on mono- and polymicrobial species biofilms and disrupted preformed biofilm on silicone as well as in microplates.
• The results of this work expand the application fields of CDH.

• Although further assay in-vivo is still needed, these results suggest the potential applicability of CSNP-DNase-CDH for wound care or as implant disinfectant to protect medical devices from polymicrobial biofilms related infections.
• Moreover, the CSNP-enzyme system could be further modified or loaded with additional drugs to obtain a higher efficiency and flexibility in targeting different biofilms.

Ferrocene-functionalized hybrid hydrogel dressing with high-adhesion for combating biofilm:

• We have designed and fabricated a multi-functional Fc-PAAM hydrogel with peroxidase-like activity, which has antibacterial, anti-biofilm properties and promotes wound healing, and can be used as a dressing for bacterial infected wounds.
• PAA was added to polyacrylamide hydrogel to improve its physical properties, and the carboxyl group of PAA was activated by EDC/NHS to form amide bond and cross-link with Fc, and a multi-functional hydrogel was prepared.
• In-vitro experiments confirmed the versatility of the hydrogel, including high adhesion, water absorption, antibacterial properties, anti-biofilm properties and promoting wound healing.

• In vivo studies have further proved that the hydrogel can effectively repair bacterial infected wounds, promote the formation of epithelial cells in inflammatory wounds, and reduce the time needed for healing.
• Taken together, the Fc-PAAM hydrogel is expected to offer broad application prospects in the treatment of postoperative wound infections caused by bacteria and in clinical microbiology

Antibiofilm poly(carboxybetaine methacrylate) hydrogels for chronic wounds dressings:

• The PCB hydrogels were shown to possess high ability to absorb large amounts of physiological solution (mimicking the wound exudate), expanding their dimensions, but not shrinking like the most available at the market.
• Due to their high swelling ability in salt solutions, the PCB hydrogels were able to absorb the collagenase and MPO, which makes them appropriate for controlling the overexpression of these deleterious enzymes in chronic wounds.
• Moreover, PCB hydrogels were demonstrated to prevent biofilm formation from S. aureus, one of the most prevalent bacterial species identified in chronic wounds.

• Moreover, PCB hydrogels were demonstrated to prevent biofilm formation from S. aureus, one of the most prevalent bacterial species identified in chronic wounds.
• The PCB hydrogels were shown to be non-cytotoxic and biocompatible as they showed little to no reaction after their implantation in-vivo in rats for 2 months.
• Additionally, the PCB hydrogels possess all characteristics of hydrogel wound dressings such as transparency, preserving wound moisture, and non-adherence to the wound.
• All these properties are advantageous for the envisaged application of PCB hydrogels as chronic wound dressings.

Development of chitosan-based hydrogel containing antibiofilm agents for the treatment of Staphylococcus aureus–infected burn wound in mice:

• In this study, two formulations containing moxifloxacin for topical delivery were prepared and confirmed for their efficacy in a MRSA-infected burn wound in BALB/c mice.
• The conventional preparation contained moxifloxacin only whereas the novel gel besides the drug contained chitosan, Boswellia gum, and EDTA, the latter two as antibiofilm agents.
• The results of this study confirm the advantage provided by the novel formulation over conventional preparation as it resulted in decreased bacterial numbers, better wound healing, and improved histopathological picture, irrespective of whether the therapy was instituted immediately or was delayed.
• The proposed novel gel can prove beneficial in the treatment of MRSA burn wound infection caused by this organism, both in planktonic and biofilm mode30.

Development of photoactive g‐C3N4/Poly(vinyl alcohol) composite hydrogel films with antimicrobial and antibiofilm activity:

• Free-standing, composite g-C3N4/PVA hydrogels have been successfully fabricated by direct casting techniques.
• Interactions between the g-C3N4 particles and the PVA polymer chains influence the mechanical and electronic properties of the resulting hydrogels as well as the associated photochemical reactivity of the incorporated semiconductor photocatalyst.
• At 6.7% g-C3N4 loading, the materials developed in this study demonstrate antimicrobial and antibiofilm activity as a result of photochemical formation of H2O2.
• Importantly, no antimicrobial or antibiofilm activity was observed for composite hydrogels that were not exposed to visible radiation.

• These results indicate that the composite materials developed in this study are not inherently toxic, despite the promising biocidal activity observed for samples exposed to visible radiation.
• This work clearly demonstrates that composite materials containing g-C3N4 are viable candidates for the development of novel functional materials for antimicrobial and antibiofilm applications.

Gentamicin decorated phosphatidylcholine-chitosan nanoparticles against biofilms and intracellular bacteria:

• In this work, gentamicin-coated phosphatidylcholine-chitosan nanoparticles (GPC Np's) were designed against biofilms and intracellular bacteria.
• Chitosan was the core of the nanoparticle, and it imparted mechanical stability to the lipid layer.
• Gentamicin adsorbed on the phosphatidylcholine surface by electrostatic adsorption.
• Gentamicin can be effectively carried into the biofilm structure by the nanosystem due to the good compatibility of the nanostructures and phospholipids and is easily phagocytosed by cells, thus making gentamicin more effective in the treatment of biofilm and intracellular bacteria.
• In addition, the GPC NPs could reduce the dosage of gentamicin and expand the application of antibiotics, which could also provide an alternative method for the treatment of a series of bacterial infections in the future.

In-situ silver nanoparticles incorporated N,O-carboxymethyl chitosan- based adhesive,self-healing,conductive,antibacterial and anti-biofilm hydrogel:

• In this work, a multifunctional in-situ forming AgNps incorporated N, O-CMC self-healing hydrogel was developed.
• The developed hydrogel exhibits self-healing property due to its metal-ligand mass transfer between Fe3+ and –COOH.
• The developed hydrogel is biocompatible, hemocompatible, and also exhibits good hemostatic potential.
• The presence of AgNps within the hydrogel exhibited linear conductivity and antibacterial properties.
• The in vitro biofilm studies revealed that the prepared N, O-CMC/AgNps hydrogel inhibits the biofilm formation due to the presence of AgNps.
• The developed N, O-CMC/AgNps hydrogel has adhesive, self-healing, conductive, antibacterial, and anti-biofilm properties.
• This N, O-CMC/AgNps hydrogel can be potentially used as a tissue sealant for infected incisional wounds.

Liposomes-in-chitosan hydrogel boosts potential of chlorhexidine in biofilm eradication in vitro:

• To address the challenges related to both treatment of chronic wounds comprising biofilms and increased antimicrobial resistance, we developed novel antimicrobial chitosan-based system.
• The system comprising liposomally-associated CHX in chitosan hydrogel exhibited superior anti-biofilm activities while maintaining properties relevant for skin administration.
• In addition, we observed anti-inflammatory effects of the chitosan hydrogel, an important feature considering wound therapy.

Low-drug resistance carbon quantum dots decorated injectable self-healing hydrogel with potent antibiofilm property and cutaneous wound healing:

• In summary, a CQDAG antibacterial hydrogel dressing with multi functions including antibiofilm, low-drug resistance, injectable, self-healing, stretchable and compressible properties, is successfully synthesized through the Schiff base linkage between amino groups of the CQDAG, CMCS and aldehyde groups on ODex.
• After decorated with CQDAG, the hydrogel possesses enhanced mechanical properties when compared with pure hydrogel.
• Besides, CQDAG could also promote self-healing effect of the hydrogel, which can be attributed to covalent bonds of Schiff base linkage between CQDAG and the polymer chains.

• Importantly, the CQDAG-hydrogel shows effectively destruction of mature S. aureus biofilm with low-drug resistance when compared to gentamicin.

• The acid-labile property of the Schiff base linkage enables the CQDAG to release from the hydrogel matrix in response to acidity generated by growing bacteria, which is beneficial for biofilm infection related therapy.
• Additionally, the CQDAG-hydrogel has good bio-compatibility with non-cytotoxicity and non-hemolysis.
• These performances afford solid fundament for the CQDAG-hydrogel to be applied to wound dressing.
• In the full-thickness skin defect model,it is significantly found that the CQDAG2 hydrogel caused a faster healing process in areas of wound, coupled with a significantly reduced degree of infection in surrounding tissues.
• Simultaneously,the granulation tissue thickness,fibroblast density,and collagen content at the wound are all better than those of commercial hydrogel dressings.
• Based on these results,we believe that the prepared multifunctional CQDAG2-hydrogel is excellent candidate as an antibacterial dressing for microbial infected wound healing without concern of drug-resistance in clinical applications.

Conclusion:

Through this powerpoint presentation, we have seen the various ways in which the anti-bacterial and anti-biofilm properties of hydrogels can be improved to make better wound dressings with greater healing properties and lesser healing periods.

Thank you.