Immobilised antimicrobial peptides in downregulation of biofilm.

Colonisation of sessile bacterial species on biotic and abiotic surfaces is responsible for the development of various infections in humans. At present, biofilm-associated chronic infections have been a prime concern among the healthcare practitioners since they are impermeable to drugs, resulting in the development of antibiotic resistance or multi-drug resistance. For a few decades, a lot of research activity has been performed in the development of alternative therapeutics to combat biofilm-associated chronic infections. The presence of extracellular polymeric substance (EPS) prevents the permeation of most of the drugs rendering drug failures. The use of small molecules has been necessary to penetrate easily through the EPS and act on the targeted cells. In present days, the use of antimicrobial peptides (AMPs) has gained immense importance as alternative therapeutics since they exhibit a novel class of antibiotics exhibiting a wide spectrum of activity and possess a low rate of development of resistance. In the last few decades, a large number of AMPs have been identified from varied groups of organisms as effector molecules for innate immune system acting as an important line of defence. In this review, we will discuss the use of AMPs as effective agents to combat various biofilm-associated chronic infections.

Docking assisted mechanistic elucidation of bio conversion of hexavalent chromium by Serratia marcescens AJRR-22 that is effective yet long term sustainable in bio-geosphere.

Environmental accumulation of hexavalent chromium [Cr(VI)] in the food chain can induce detrimental effects on plants and animals, which calls for effective remediation strategies using biological entities. The bacterium isolated from an iron mine in Odisha, India, is identified asSerratia marcescensAJRR-22. This multi-metal tolerant strain is capable of bio-converting up to 350 mg/L Cr(VI) within 72 h of incubation. Observable electron dense precipitates in transmission electron microscopic images, data patterns in fluorescence microscopy and flow cytometry clearly reveal the chromate reduction ability of the strain. The molecular study is depicted by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopic analyses. Furthermore, a simulation study to estimate the interactions of chromium bound flavin reductasewith predicted docked complexes suggests significant negative Gibbs free energy and a low inhibition constant (Ki), signifying strong spontaneous binding of Cr(VI) to the enzyme, which makes the strain an efficient candidate for chromium bioremediation.

Role of Virus on Oral Biofilm: Inducer or Eradicator?

Sessile forms of bacteria remain as an aggregation on biotic and abiotic surfaces, known as biofilm, that protects them from various environmental stress, like antibiotic and host immune response. The oral cavity is enriched with microbial biofilm, formed on dental surface, gingival plaques, and associated tissue. Several pathogenic viruses enter the oral cavity and form biofilms either on pre-existing biofilms or on cell surfaces. They achieved persistence and the ability to prompt dissemination in the biofilm. Dental biofilms of COVID-19 patients are found to harbor SARS-CoV-2 RNA and may act as a budding reservoir, which also promotes COVID-19 transmission. On the other hand, most of the prokaryotic viruses or bacteriophages essentially kill the host bacteria and thereby destroy the biofilm. Bacteria try to evade from phage attack by concealing in biofilm, whereas the eukaryotic virus often utilize bacterial biofilm to escape host's immune response and to achieve an easy way of dissemination. The opposite action of viruses as an inducer and eradicator of biofilm has made the oral biofilm a unique ecosystem.

Biogenic silver nanoparticles (AgNPs) from Tinosporacordifolia leaves: An effective antibiofilm agent against Staphylococcus aureus ATCC 23235.

Medicinal plants are long known for their therapeutic applications. Tinospora cordifolia (commonly called gulancha or heart-leaved moonseed plant), a herbaceous creeper widely has been found to have antimicrobial, anti-inflammatory, anti-diabetic, and anti-cancer properties. However, there remains a dearth of reports regarding its antibiofilm activities. In the present study, the anti-biofilm activities of phytoextractof T. cordifolia and the silver nanoparticles made from this phytoextract were tested against the biofilm of S.taphylococcus aureus, one of the major nosocomial infection-producing bacteria taking tetracycline antibiotic as control. Both phytoextract from the leaves of T. cordifolia, and the biogenic AgNPs from the leaf extract of T. cordifolia, were found successful in reducing the biofilm of Staphylococcus aureus. The biogenic AgNPs formed were characterized by UV- Vis spectroscopy, Field emission Scanning Electron Microscopy (FE- SEM), and Dynamic light scattering (DLS) technique. FE- SEM images showed that the AgNPs were of size ranging between 30 and 50 nm and were stable in nature, as depicted by the zeta potential analyzer. MIC values for phytoextract and AgNPs were found to be 180 mg/mL and 150 µg/mL against S. aureusrespectively. The antibiofilm properties of the AgNPs and phytoextract were analyzed using the CV assay and MTT assay for determining the reduction of biofilms. Reduction in viability count and revival of the S. aureus ATCC 23235 biofilm cells were analyzed followed by the enfeeblement of the EPS matrix to quantify the reduction in the contents of carbohydrates, proteins and eDNA. The SEM analyses clearly indicated that although the phytoextracts could destroy the biofilm network of S. aureuscells yet the biogenicallysynthesizedAgNPs were more effective in biofilm disruption. Fourier Transformed Infrared Radiations (FT- IR) analyses revealed that the AgNPs could bring about more exopolysaccharide (EPS) destruction in comparison to the phytoextract. The antibiofilm activities of AgNPs made from the phytoextract were found to be much more effective than the non-conjugated phytoextract, indicating the future prospect of using such particles for combatting biofilm-mediated infections caused by S aureus.

Marine bioactive compounds as antibiofilm agent: a metabolomic approach.

The ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.

Purification, Characterization, and Application of Endoglucanase from Rhizopus oryzae as Antibiofilm Agent.

The enzyme endoglucanase is responsible for the depolymerization of cellulose. This study focuses on characterization and purification of endoglucanase from Rhizopus oryzae MTCC 9642 through a simple size exclusion method and its effective application as an antibiofilm agent. Extracellular ß-1,4-endoglucanase, an enzyme that catalyzes the hydrolysis of carboxymethyl cellulose, was found to be synthesized by Rhizopus oryzae MTCC 9642. The enzyme was purified up to homogeneity simply by size exclusion process through ultrafiltration and gel chromatography. The molecular weight of purified enzyme protein was estimated to be 39.8 kDa and it showed the highest substrate affinity towards carboxymethyl-cellulose with Km and Vmax values of 0.833 mg ml-1 and of 0.33 mmol glucose min-1 mg-1protein, respectively. The purified enzyme exhibited optimal activity at pH 6 with a broad stability range of pH 3-8. The most preferred temperature was 35 °C and 50% of activity could be retained after the thermal exposure at 40 °C for 25 min. The purified enzyme protein was inactivated by Cu2+, while the activity could be enhanced by the addition of exogenous thiols. Since biofilm is a challenge for health sector, with the aim of eradicating the biofilm, the purified endoglucanase was used to remove biofilm produced by two nosocomial bacteria. As predicted by in silico molecular docking interaction, the purified enzyme could effectively degrade biofilm architecture of bacterial strains S. aureus and P. aeruginosa by 76.52 ± 6.52% and 61.67 ± 8.76%, respectively. The properties of purified enzyme protein, as elucidated by in vitro and in silico characterization, may be favourable for its commercial applications as a potent antibiofilm agent.

Analysis of Antibiofilm Activities of Bioactive Compounds from Honeyweed (Leonurus sibiricus) Against P. aeruginosa: an In Vitro and In Silico Approach.

Leonurus sibiricus (Red verticilla, honeyweed) is a type of herbaceous plant predominantly found in Asian subcontinents as weed in crop fields and is widely used for treating diabetes, bronchitis, and menstrual irregularities. However, there is a dearth of study in the application of the plant phytocompounds for treating biofilm-associated chronic infections. The bioactive compounds mainly comprise of tri-terpenes, di-terpenes, phenolic acid, and flavonoids which may have potential role as antimicrobial and antibiofilm agents. Acute and chronic infection causing microbes usually form biofilm and develop virulence factors and antibiotic resistance through quorum sensing (QS). In this study, the bioactive compounds leosibirin, sibiricinone A, leosibirone A, leonotin, quercetin, lavandulifolioside, and myricetin were identified using GC-MS analysis. These were used for analyzing the antibiofilm and anti-quorum sensing activities (rhamnolipid, AHL assay, swarming motility assay) against the biofilm formed by Pseudomonas aeruginosa, the most significant nosocomial disease-causing bacteria. The compounds were able to bring about maximum inhibition in biofilm formation and QS. Although the antibiofilm activity of the phytoextract was found to be higher than that of individual phytocompounds at a concentration of 250 µg/mL, quercetin and myricetin showed highest antibiofilm activity against Pseudomonas aeruginosa, respectively, at MIC values of 135 µg/mL and 150 µg/mL against P aeruginosa. FT-IR study also revealed that the active ingredients were able to bring about the destruction of exopolysaccharides (EPS). These observations were further validated by molecular docking interactions that showed the active ingredients inhibit the functioning of QS sensing proteins by binding with them. It was observed that myricetin showed better interactions with the QS proteins of P. aeruginosa. Myricetin and quercetin show considerable inhibition of biofilm in comparison to the phytocompounds. Thus, the present study suggests that the active compounds from L. sibiricus can be used as an alternate strategy in inhibiting the biofilm formed by pathogenic organisms.

Periodontitis: An Oral Disease with Severe Consequences.

Periodontitis, being a multifactorial disorder is found to be the most common oral disease denoted by the inflammation of gingiva and resorption of tooth supporting alveolar bone. The disease being closely linked with fast life style and determined by unhygienic behavioural factors, the internal milieu of oral cavity and formation of plaque biofilm on the dental and gingival surfaces. Porphyromonas gingivalis, being the major keystone pathogen of the periodontal biofilm evokes host immune responses that causes damage of gingival tissues and resorption of bones. The biofilm associated microbial community progressively aggravates the condition resulting in chronic inflammation and finally tooth loss. The disease often maintains bidirectional relationship with different systemic, genetic, autoimmune, immunodeficiency diseases and even psychological disorders. The disease can be diagnosed and predicted by various genetic, radiographic and computer-aided design (CAD) & computer-aided engineering (CAE) and artificial neural network (ANN). The elucidation of genetic background explains the inheritance of the disease. The therapeutic approaches commonly followed include mechanical removal of dental plaque with the use of systemic antibiotics. Awareness generation amongst local people, adoption of good practice of timely tooth brushing preferably with fluoride paste or with nanoconjugate pastes will reduce the chance of periodontal plaque formation. Modern tissue engineering technology like 3D bioprinting of periodontal tissue may help in patient specific flawless regeneration of tooth structures and associated bones.

Bacteriocin: A natural approach for food safety and food security.

The call to cater for the hungry is a worldwide problem in the 21st century. Food security is the utmost prime factor for the increasing demand for food. Awareness of human health when using chemical preservatives in food has increased, resulting in the use of alternative strategies for preserving food and enhancing its shelf-life. New preservatives along with novel preservation methods have been instigated, due to the intensified demand for extended shelf-life, along with prevention of food spoilage of dairy products. Bacteriocins are the group of ribosomally synthesized antimicrobial peptides; they possess a wide range of biological activities, having predominant antibacterial activity. The bacteriocins produced by the lactic acid bacteria (LAB) are considered to be of utmost importance, due to their association with the fermentation of food. In recent times among various groups of bacteriocins, leaderless and circular bacteriocins are gaining importance, due to their extensive application in industries. These groups of bacteriocins have been least studied as they possess peculiar structural and biosynthetic mechanisms. They chemically possess N-to-C terminal covalent bonds having a predominant peptide background. The stability of the bacteriocins is exhibited by the circular structure. Up till now, very few studies have been performed on the molecular mechanisms. The structural genes associated with the bacteriocins can be combined with the activity of various proteins which are association with secretion and maturation. Thus the stability of the bacteriocins can be used effectively in the preservation of food for a longer period of time. Bacteriocins are thermostable, pH-tolerant, and proteolytically active in nature, which make their usage convenient to the food industry. Several research studies are underway in the domain of biopreservation which can be implemented in food safety and food security.

Anti-biofilm efficacy of green-synthesized ZnO nanoparticles on oral biofilm: In vitro and in silico study.

The development of biofilm on the biotic and abiotic surfaces is the greatest challenge for health care sectors. At present times, oral infection is a common concern among people with an unhealthy lifestyle and most of these biofilms-associated infections are resistant to antibiotics. This has increased a search for the development of alternate therapeutics for eradicating biofilm-associated infection. Nanobiotechnology being an effective way to combat such oral infections may encourage the use of herbal compounds, such as bio-reducing and capping agents. Green-synthesis of ZnO nanoparticles (ZnO NP) by the use of the floral extract of Clitoria ternatea, a traditionally used medicinal plant, showed stability for a longer period of time. The NPs as depicted by the TEM image with a size of 10 nm showed excitation spectra at 360 nm and were found to remain stable for a considerable period of time. It was observed that the NPs were effective in the eradication of the oral biofilm formed by the major tooth attacking bacterial strains namely Porphyromonsas gingivalis and Alcaligenes faecalis, by bringing a considerable reduction in the extracellular polymeric substances (EPS). It was observed that the viability of the Porphyromonsas gingivalis and Alcaligenes faecalis was reduced by NP treatment to 87.89 ± 0.25% in comparison to that of amoxicillin. The results went in agreement with the findings of modeling performed by the use of response surface methodology (RSM) and artificial neural network (ANN). The microscopic studies and FT-IR analysis revealed that there was a considerable reduction in the biofilm after NP treatment. The in silico studies further confirmed that the ZnO NPs showed considerable interactions with the biofilm-forming proteins. Hence, this study showed that ZnO NPs derived from Clitoria ternatea can be used as an effective alternative therapeutic for the treatment of biofilm associated oral infection.

Lactic Acid Bacteria (LAB): Autochthonous and Probiotic Microbes for Meat Preservation and Fortification.

The enhanced concern of the consumers regarding the safety, quality of the food products, and avoidance of the use of chemical food preservatives has resulted in a breakthrough in biopreservation. This has resulted in the use of beneficial microbial species, including bacteria and their secondary metabolites, to enhance the shelf-life and quality of the food products. Meat preservation and fortification are among the biggest concerns, as they are relevant to the majority of food products. The chemical preservatives conventionally used in preserving meat and meat products possess several detrimental effects on the consumers. Thus, alternative strategies are needed to combat strategically in facilitating the shelf-life and quality. Lactic acid bacteria (LAB) are considered the safest organism and have a profound role in food and food-processing industries. The biofilm developed by the bacteria prevents the growth of various undesirable microorganisms on meat and meat products. Various studies depicted that LAB produces various antimicrobial metabolites that can act effectively on the food-degrading pathogens, rendering it safe and enhancing shelf-life. This review, thus, deals with the use of LAB as biopreservatives for enhancing the shelf-life of meat and meat products and helping its fortification.

Microbiomics for enhancing electron transfer in an electrochemical system.

In microbial electrochemical systems, microorganisms catalyze chemical reactions converting chemical energy present in organic and inorganic molecules into electrical energy. The concept of microbial electrochemistry has been gaining tremendous attention for the past two decades, mainly due to its numerous applications. This technology offers a wide range of applications in areas such as the environment, industries, and sensors. The biocatalysts governing the reactions could be cell secretion, cell component, or a whole cell. The electroactive bacteria can interact with insoluble materials such as electrodes for exchanging electrons through colonization and biofilm formation. Though biofilm formation is one of the major modes for extracellular electron transfer with the electrode, there are other few mechanisms through which the process can occur. Apart from biofilm formation electron exchange can take place through flavins, cytochromes, cell surface appendages, and other metabolites. The present article targets the various mechanisms of electron exchange for microbiome-induced electron transfer activity, proteins, and secretory molecules involved in the electron transfer. This review also focuses on various proteomics and genetics strategies implemented and developed to enhance the exo-electron transfer process in electroactive bacteria. Recent progress and reports on synthetic biology and genetic engineering in exploring the direct and indirect electron transfer phenomenon have also been emphasized.

Precision targeting of food biofilm-forming genes by microbial scissors: CRISPR-Cas as an effective modulator.

The abrupt emergence of antimicrobial resistant (AMR) bacterial strains has been recognized as one of the biggest public health threats affecting the human race and food processing industries. One of the causes for the emergence of AMR is the ability of the microorganisms to form biofilm as a defense strategy that restricts the penetration of antimicrobial agents into bacterial cells. About 80% of human diseases are caused by biofilm-associated sessile microbes. Bacterial biofilm formation involves a cascade of genes that are regulated via the mechanism of quorum sensing (QS) and signaling pathways that control the production of the extracellular polymeric matrix (EPS), responsible for the three-dimensional architecture of the biofilm. Another defense strategy utilized commonly by various bacteria includes clustered regularly interspaced short palindromic repeats interference (CRISPRi) system that prevents the bacterial cell from viral invasion. Since multigenic signaling pathways and controlling systems are involved in each and every step of biofilm formation, the CRISPRi system can be adopted as an effective strategy to target the genomic system involved in biofilm formation. Overall, this technology enables site-specific integration of genes into the host enabling the development of paratransgenic control strategies to interfere with pathogenic bacterial strains. CRISPR-RNA-guided Cas9 endonuclease, being a promising genome editing tool, can be effectively programmed to re-sensitize the bacteria by targeting AMR-encoding plasmid genes involved in biofilm formation and virulence to revert bacterial resistance to antibiotics. CRISPRi-facilitated silencing of genes encoding regulatory proteins associated with biofilm production is considered by researchers as a dependable approach for editing gene networks in various biofilm-forming bacteria either by inactivating biofilm-forming genes or by integrating genes corresponding to antibiotic resistance or fluorescent markers into the host genome for better analysis of its functions both in vitro and in vivo or by editing genes to stop the secretion of toxins as harmful metabolites in food industries, thereby upgrading the human health status.

Multi-Omics Approach in Amelioration of Food Products.

Determination of the quality of food products is an essential key factor needed for safe-guarding the quality of food for the interest of the consumers, along with the nutritional and sensory improvements that are necessary for delivering better quality products. Bacteriocins are a group of ribosomally synthesized antimicrobial peptides that help in maintaining the quality of food. The implementation of multi-omics approach has been important for the overall enhancement of the quality of the food. This review uses various recent technologies like proteomics, transcriptomics, and metabolomics for the overall enhancement of the quality of food products. The matrix associated with the food products requires the use of sophisticated technologies that help in the extraction of a large amount of information necessary for the amelioration of the food products. This review would provide a wholesome view of how various recent technologies can be used for improving the quality food products and for enhancing their shelf-life.

Citrus Essential Oils: a Treasure Trove of Antibiofilm Agent.

Biofilms are groups of adherent cell communities that cohere to the biotic and abiotic surfaces with the help of extracellular polymeric substances (EPS). EPS allow bacteria to form a biofilm that facilitates their binding to biotic and abiotic surfaces and provides resistance to the host immune responses and to antibiotics. There are efforts that have led to the development of natural compounds that can overcome this biofilm-mediated resistance. Essential oils (EOs) are a unique mixture of compounds that plays a key role in preventing the development of biofilm. The present overview focusses on the role of various types of citrus essential oils in acting against the biofilm, and the antibiofilm properties of natural compounds that may show an avenue to treat the multidrug-resistant bacteria.

Immobilized enzymes as potent antibiofilm agent.

Biofilm has been a point of concern in hospitals and various industries. They not only cause various chronic infections but are also responsible for the degradation of various medical appliances. Since the last decade, various alternate strategies are being adopted to combat the biofilm formed on various biotic and abiotic surfaces. The use of enzymes as a potent anti-fouling agent is proved to be of utmost importance as the enzymes can inhibit biofilm formation in an eco-friendly and cost-effective way. The physical and chemical immobilization of the enzyme not only leads to the improvement of thermostability and reusability of the enzyme, but also gains better efficiency of biofilm removal. Immobilization of amylase, cellobiohydrolase, pectinase, subtilisin A and ß-N-acetyl-glucosaminidase (DspB) are proved to be most effective in inhibition of biofilm formation and removal of matured biofilm than their free forms. Hence, these immobilized enzymes provide greater eradication of biofilm formed on various surfaces and are coming up to be the potent antibiofilm agent.

Seafood Discards: A Potent Source of Enzymes and Biomacromolecules With Nutritional and Nutraceutical Significance.

In recent times, the seafood industry is found to produce large volumes of waste products comprising shrimp shells, fish bones, fins, skins, intestines, and carcasses, along with the voluminous quantity of wastewater effluents. These seafood industry effluents contain large quantities of lipids, amino acids, proteins, polyunsaturated fatty acids, minerals, and carotenoids mixed with the garbage. This debris not only causes a huge wastage of various nutrients but also roots in severe environmental contamination. Hence, the problem of such seafood industry run-offs needs to be immediately managed with a commercial outlook. Microbiological treatment may lead to the valorization of seafood wastes, the trove of several useful compounds into value-added materials like enzymes, such as lipase, protease, chitinase, hyaluronidase, phosphatase, etc., and organic compounds like bioactive peptides, collagen, gelatin, chitosan, and mineral-based nutraceuticals. Such bioconversion in combination with a bio-refinery strategy possesses the potential for environment-friendly and inexpensive management of discards generated from seafood, which can sustainably maintain the production of seafood. The compounds that are being produced may act as nutritional sources or as nutraceuticals, foods with medicinal value. Determining utilization of seafood discard not only reduces the obnoxious deposition of waste but adds economy in the production of food with nutritional and medicinal importance, and, thereby meets up the long-lasting global demand of making nutrients and nutraceuticals available at a nominal cost.

Engineered Biofilm: Innovative Nextgen Strategy for Quality Enhancement of Fermented Foods.

Microbial communities within fermented food (beers, wines, distillates, meats, fishes, cheeses, breads) products remain within biofilm and are embedded in a complex extracellular polymeric matrix that provides favorable growth conditions to the indwelling species. Biofilm acts as the best ecological niche for the residing microbes by providing food ingredients that interact with the fermenting microorganisms' metabolites to boost their growth. This leads to the alterations in the biochemical and nutritional quality of the fermented food ingredients compared to the initial ingredients in terms of antioxidants, peptides, organoleptic and probiotic properties, and antimicrobial activity. Microbes within the biofilm have altered genetic expression that may lead to novel biochemical pathways influencing their chemical and organoleptic properties related to consumer acceptability. Although microbial biofilms have always been linked to pathogenicity owing to its enhanced antimicrobial resistance, biofilm could be favorable for the production of amino acids like l-proline and L-threonine by engineered bacteria. The unique characteristics of many traditional fermented foods are attributed by the biofilm formed by lactic acid bacteria and yeast and often, multispecies biofilm can be successfully used for repeated-batch fermentation. The present review will shed light on current research related to the role of biofilm in the fermentation process with special reference to the recent applications of NGS/WGS/omics for the improved biofilm forming ability of the genetically engineered and biotechnologically modified microorganisms to bring about the amelioration of the quality of fermented food.

Engineered Nanotechnology: An Effective Therapeutic Platform for the Chronic Cutaneous Wound.

The healing of chronic wound infections, especially cutaneous wounds, involves a complex cascade of events demanding mutual interaction between immunity and other natural host processes. Wound infections are caused by the consortia of microbial species that keep on proliferating and produce various types of virulence factors that cause the development of chronic infections. The mono- or polymicrobial nature of surface wound infections is best characterized by its ability to form biofilm that renders antimicrobial resistance to commonly administered drugs due to poor biofilm matrix permeability. With an increasing incidence of chronic wound biofilm infections, there is an urgent need for non-conventional antimicrobial approaches, such as developing nanomaterials that have intrinsic antimicrobial-antibiofilm properties modulating the biochemical or biophysical parameters in the wound microenvironment in order to cause disruption and removal of biofilms, such as designing nanomaterials as efficient drug-delivery vehicles carrying antibiotics, bioactive compounds, growth factor antioxidants or stem cells reaching the infection sites and having a distinct mechanism of action in comparison to antibiotics-functionalized nanoparticles (NPs) for better incursion through the biofilm matrix. NPs are thought to act by modulating the microbial colonization and biofilm formation in wounds due to their differential particle size, shape, surface charge and composition through alterations in bacterial cell membrane composition, as well as their conductivity, loss of respiratory activity, generation of reactive oxygen species (ROS), nitrosation of cysteines of proteins, lipid peroxidation, DNA unwinding and modulation of metabolic pathways. For the treatment of chronic wounds, extensive research is ongoing to explore a variety of nanoplatforms, including metallic and nonmetallic NPs, nanofibers and self-accumulating nanocarriers. As the use of the magnetic nanoparticle (MNP)-entrenched pre-designed hydrogel sheet (MPS) is found to enhance wound healing, the bio-nanocomposites consisting of bacterial cellulose and magnetic nanoparticles (magnetite) are now successfully used for the healing of chronic wounds. With the objective of precise targeting, some kinds of "intelligent" nanoparticles are constructed to react according to the required environment, which are later incorporated in the dressings, so that the wound can be treated with nano-impregnated dressing material in situ. For the effective healing of skin wounds, high-expressing, transiently modified stem cells, controlled by nano 3D architectures, have been developed to encourage angiogenesis and tissue regeneration. In order to overcome the challenge of time and dose constraints during drug administration, the approach of combinatorial nano therapy is adopted, whereby AI will help to exploit the full potential of nanomedicine to treat chronic wounds.