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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 12  |  Issue : 6  |  Page : 504-511

A review on biofilm and biomaterials: Prosthodontics and periodontics perspective


1 Private Practitioner, France
2 Department of Prosthetic Dentistry, College of Dentistry, Jouf University, Sakakah, Saudi Arabia
3 Department of Preventive Dentistry, College of Dentistry, Jouf University, Sakakah, Saudi Arabia
4 Department of Oral & Maxillofacial Surgery & Diagnostic Sciences, College of Dentistry, Jouf University, Sakakah, Saudi Arabia

Date of Submission03-Jun-2020
Date of Decision05-Aug-2020
Date of Acceptance20-Oct-2020
Date of Web Publication30-Nov-2020

Correspondence Address:
Dr. Kiran Kumar Ganji
College of Dentistry, Jouf University, Sakaka.
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIOH.JIOH_199_20

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  Abstract 

Aim: Biofilm bacteria show coordinated behavior with heterogeneous bacterial communities and complex three-dimensional structures. Biofilm formation on dental implants occurs in a manner similar to that of a natural tooth. Bacterial adhesion occurs after pellicle formation. Therefore, to reduce bacterial adhesion, the biomaterial surface can be modified, thereby lowering the scope of biofilm formation. This review aimed to understand the mechanism of biofilm formation; the most common microorganisms associated with a biofilm, nature of the bonds to the host tissue, and the methods to overcome biofilm formation and associated infectious diseases from dental materials and implants. Materials and Methods: A comprehensive literature search was conducted on published articles using internet search databases such as PubMed, EBSCO, Cochrane library, Embase, HMIC, Web of Science, Google Scholar, and Directory of Open Access using keywords such as biofilm, quorum sensing, implant-related biofilm formation, and biofilm control. Results: A total of 121 articles published from March 2007 to May 2020 were screened during the review process, of which only 33 articles were selected for this study. Surface roughness is directly proportional to bacterial aggregation. PEEK is a modified functional peptide nanoparticle-coated biomaterial that manifests antibacterial activity against gram-negative Escherichia coli and gram-positive Staphylococcus aureus. Conclusions: New strategies are to be followed to control biofilm-mediated implant infections. Clinicians should extensively adopt newer techniques to deal with biofilm-mediated therapeutic challenges.

Keywords: Biofilm, Dental Materials, Implants, Quorum Sensing


How to cite this article:
Toumeh TT, Sghaireen MG, Ganji KK, Mathew M, Nagy AI, Rao K. A review on biofilm and biomaterials: Prosthodontics and periodontics perspective. J Int Oral Health 2020;12:504-11

How to cite this URL:
Toumeh TT, Sghaireen MG, Ganji KK, Mathew M, Nagy AI, Rao K. A review on biofilm and biomaterials: Prosthodontics and periodontics perspective. J Int Oral Health [serial online] 2020 [cited 2022 Dec 6];12:504-11. Available from: https://www.jioh.org/text.asp?2020/12/6/504/301849


  Introduction Top


Biofilm is a bacterial complex that adheres to a hard or nonexuviating surface by secreting a sticky, extracellular polymeric substance; thus, biofilm cannot be removed easily by gentle rinsing.[1] Biofilm formation is an ancient prokaryotic adaptation that begins when a planktonic bacterium adheres to material such as wood, metal, plastic, living tissues, or even stagnant water. The thickness of a biofilm ranges from a single cell to several inches, depending on the surrounding conditions.[2] Biofilm bacteria show coordinated behavior with heterogeneous bacterial communities and complex three-dimensional structures. Therefore, biofilms generally express different surface molecules, antibiotic resistance, nutrient utilization, and virulence factors.[2],[3] Biofilm bacteria do not stick together; instead, they form an organized community with specialized configurations. Microorganisms present in a biofilm coordinate and survive via quorum sensing, thus making many biofilms antibiotic resistant. Therefore, biofilm bacteria reach a critical cell density easily and express virulence that overcomes the host defense mechanism leading to infectious diseases.[3] Apart from bacteria, a biofilm comprises of other microorganisms such as fungi, protozoa, and microalgae are also enclosed in a biofilm.[4]

Biofilms are involved in a variety of human infections such as endocarditis, osteomyelitis, chronic otitis media, gastrointestinal ulcers, urinary tract infection, chronic lung infection in cystic fibrosis, dental caries, periodontitis, and foreign body associated infections.[5] Foreign body-related infections are common in functional restorative prosthesis such as heart valves, venous catheters, vascular prosthesis, fracture fixation devices, breast implants, intraocular lenses, denture bases, maxillofacial reconstruction prosthesis, and dental implants.[4],[6] These infections can lead to fatal complications.[4],[6] LuxS/autoinducer-2 produced by both gram-positive and gram-negative bacteria enables cell-to-cell communication.[5] The cell-to-cell communication established helps in both metabolic and gene exchange through quorum sensing.[3]

A biofilm matrix is composed of exopolysaccharides, proteins, teichoic acids, lipids, and extracellular DNA. Antibiotics are only partially effective in biofilm destruction. The exact reason is not entirely understood; however, the existence of slow-growing bacteria and different microorganisms with different phenotypic levels of resistance, and quorum sensing of bacteria and other microorganisms are some of the important factors that cause antibiotic resistance in biofilms.[2],[3],[7] This review aimed to understand the mechanism of biofilm formation; the most common microorganisms detected in a biofilm, nature of the bonds to the host tissue, and the methods to overcome biofilm formation and associated infectious diseases from dental materials and implants.


  Materials and Methods Top


This review has been conducted on published articles using internet search databases such as PubMed, EBSCO, Cochrane Library, Embase, HMIC, Web of Science, Google Scholar, and Directory of Open Access using keywords such as biofilm, quorum sensing, implant-related biofilm formation, and biofilm control. The types of articles included were randomized control trials (RCTs), clinical trials, in vivo studies, and in vitro studies. Review articles and original research articles related to the effect of biofilm and the control of biofilm in natural dentition were excluded. A total of 121 articles published from March 2007 to May 2020 were screened during the review process and based on the objective of the study only 33 articles were found to be suitable for review.


  Results Top


The process of deciding the inclusion criteria is explained using a flow chart [Figure 1]. The screened articles were assessed independently by two separate authors to prevent bias [Table 1] and [Table 2].
Figure 1: Flow diagram of selection process

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Table 1: Biofilm formation on dental materials and comparative studies

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Table 2: Control of biofilm formation on dental materials and comparative studies

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  Discussion Top


Biofilm and dental biomaterials

Adhesion of the bacteria to the biomaterial surface is the initial step in the pathogenesis of biomaterial-related biofilm infections. Initial interaction between the bacteria and the biomaterial is nonspecific and driven by different forces such as electrostatic and van der Waals forces. During this phase, the bacteria are passively adsorbed on the biomaterial surface, and the process is nurtured by specific proteins such as autolysins in the presence of body fluids. Active stable anchorage is thus established by autolysin adhesions, which bind to the host proteins that are adsorbed onto the biomaterial surface. The colonized bacteria later mature, and characteristic features specific to these bacterial colonies develop. Finally, these bacteria return to their initial planktonic form, which is then ready for a new invasive phase elsewhere [Figure 2].[8] A variety of biomaterials are used in dentistry for different applications. Factors such as surface roughness, surface energy, surface topography, and composition influence biofilm formation on the dental biomaterial surface.[9]
Figure 2: Schematic representation of biofilm formation on dental materials[38]

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Low surface energy reduces bacterial adhesion to the surface. With the exception of dental ceramics, majority of the dental materials show higher surface energy than that of enamel, which leads to the risk of biofilm formation. Surface roughness and complicated surface topography leads to bacterial adhesion and biofilm formation. The rougher the surface, the greater the bacterial adhesion can be seen. The species adhered to the biomaterial surface is independent of the surface roughness. As the surface roughness increases, the surface area also increases, and this leads to the formation of more secure pockets for pellicle attachment.[9],[10] The threshold surface roughness (Ra) value for bacterial biofilm formation is suggested to be about 0.2 µm. Although bacterial adhesion occurs below this level, it can be removed easily by cleaning.[10]

Chemical composition of the biomaterial is another important factor which influences biofilm formation. The components of the biomaterial sometimes get attracted or attached to proteins and microorganisms via van der Waals forces, acid-base reactions, and electrostatic forces. The material and restoration type used, the morphology, and the location of the biomaterial are other important factors that control biofilm formation.[8],[10]

The poly (methyl methacrylate) polymer also known as acrylic resin has a wide variety of applications in the medical and dental field. Among these, intraocular lenses, bone cement, maxillofacial prosthesis, and denture fabrication are popular applications of this material. The species isolated from the surface of acrylic mainly consists of Candida species with Candida albicans dominant followed by C. glabrata. Other Candida species isolated are Candida dubliniensis, C. parapsilosis, C. krusei, and C. tropicalis. They are capable of causing severe denture stomatitis leading to burning sensation and pain coupled with altered taste sensation.[8]

Biofilm formation on restorative resins can result in serious deterioration of the restoration. Increased surface roughness, filler particle exposure, and decreased surface hardness of these restorations occur after exposure to a biofilm. Research has shown that the biofilm formed on conventional glass ionomer cement (GIC) restoration stimulates surface degradation under a favorable environment of acidic fluid intake, temperature fluctuation, and the presence of saliva. Streptococcus mutans is the main species isolated from the surface of the restoration, and it contributed to the increase in surface roughness from 0.1 to 1 µm after 1 month of biofilm formation. Fluoride released from GIC can act as a buffer to neutralize the acids produced by the bacteria, suppressing bacterial adhesion, and thus, biofilm formation. The thin biofilm formed on GIC has low viability. However, the concentration and time period of the fluoride released from GIC controls the anti-cariogenic property of this material.[8]

Streptococcus mutans and Lactobacillus are normally isolated from the margins of composite resin restorations. Release of nonpolymerized monomers like ethylene glycol dimethacrylate (EGDMA), diethylene glycol dimethacrylate (DEGDMA), and triethylene glycol dimethacrylate (TEGDMA) into the oral cavity promotes the growth of S. mutans and Lactobacillus; these contribute to caries formation on composite restoration.[11] Bacterial growth due to the presence of EGDMA was measured as optical degrapnsity in a study that suggested that the higher optical density was not due to an increase in the number of bacteria, but the larger size of the bacteria. A vesicular substance found surrounding the bacteria, which unveiled a composition matching that of EGDMA, indicates the role of this monomer in biofilm formation and caries initiation.[11] The components of dentin bonding agents such as hydroxyethyl methacrylate and triethylene glycol methacrylate contribute to the growth of Streptococcus sobrinus and Lactobacillus species. The degree of conversion of monomer into polymer thus shows a key role in biofilm formation in composite resin restorations. Maximum polymerization of the composite resin restoration can be achieved by using the light-curing and incremental technique. Addition of the resin layer by layer and allowing time for polymerization enhances the degree of conversion. Presence of oxygen during polymerization inhibits the reaction and leaves unreacted monomer in the restoration.[11]

Biofilm and dental implants

Dental implants, most commonly made of titanium (Ti), are inserted into the alveolar bone to serve as an artificial root. It is exposed to oral microflora as it penetrates through the oral mucosa. The polished surface of the dental implant is commonly exposed to the oral cavity and can be cleaned. A dental implant usually consists of many small components joined together with small screws. Therefore, a minute gap or crevice will always exist between these screws which generate a very favorable and secure space for bacteria to adhere and grow. This leads to inflammation and the suppression of osseointegration.[10]

In order to achieve early osseointegration, modern implants usually have a very rough surface. If osseointegration is delayed, it causes bacterial colonization and aggregation; thereby resulting in implant failure due to peri-implantitis. The implant is connected directly to bone; therefore, any inflammation enters into the blood stream quicker than any other oral cavity-related inflammation.[10] Thus, peri-implant biofilm formation is one of the main reasons for implant failure.[12]

Biofilm formed on an implant is the same as that of a natural tooth. Bacterial adhesion occurs after pellicle formation. It then proliferates by cell-to-cell attachment through the quorum sensing mechanism. This leads to secondary colonization and cell aggregation.[12] Biofilm formation around teeth occurs immediately after cleaning and colonies of specific species are formed within 6h. A clean tooth surface is prone to have remnants of unattached microbiota, which multiply immediately and provide a convenient site for secondary species attachment. In the case of newly placed implants, the primary microbial colony is absent and it undergoes the initial stage for bacterial colonization.[13] The initial bacterial colony formed comprises mainly of gram-positive bacteria such as the Actinomyces species. Later, a secondary colony forms with Fusobacterium bridging as in the case of oral biofilm formation.[14]

Titanium is the material of choice due to its advantageous properties such as biocompatibility, chemical inertness, corrosion resistance, stability, and its various physical and mechanical properties. It remains a gold standard for dental implant abutments, right from its introduction in dentistry.[15] Titanium-based allergic reactions have not yet been reported in dental literatures.[16] however, an increase in the demand for esthetics led to the search for other tooth-like materials such as ceramic and zirconium-based implants.[15]

Ceramics were introduced initially into dentistry as a surface coating material on metal-based endosseous implants to improve osseointegration. Bioactive ceramics, such as calcium phosphate and bioglass, and inert ceramics such as aluminum oxide and zirconium oxide, were used as surface coating materials.[16] Zirconium-based implants show more bone-implant contact (BIC) than alumina-based ceramic implants.[17] In the search for surpassing the inherent brittle nature of ceramic materials and for the improvement of fracture resistance under complex mechanical loading in the oral environment, another material, yttria-stabilized tetragonal zirconia polycrystal ceramic referred to as “ceramic steel,” was introduced as a dental implant material. It possesses excellent physical, biological, chemical, and mechanical properties. Crystallographic transformations occur in zirconia-based ceramics with temperature change. At higher temperatures, zirconia shows a strong tetrahedral structure, which, on cooling, transforms into a monoclinic structure. This causes a reduction in the strength of zirconia-based ceramics. Yttria is added to zirconia to stabilize this tetrahedral structure even at room temperature to provide better strength.[17] However, the biological properties of this material are comparable to those of titanium implants. Various other properties such as low surface porosity, high density, high bending, and high compression strength have made this material suitable for dental applications such as crowns, fixed partial dentures, implants, and abutments.[17],[18]

Biocompatibility of zirconium-based ceramic implants was investigated based on the connective tissue as it is the most common site for microorganisms. Various physical forms of zirconia such as yttria-stabilized ceramic, magnesium oxide, aluminum, and calcium incorporated ceramics were considered for biocompatibility testing. The results proved that ceramic is a biocompatible material. However, the wear products of zirconia showed some toxicity. Zirconia-based dental implants are also biocompatible with immune cells such as monocytes, lymphocytes, and macrophages as there was no evidence of toxicity. Tests on osteoblasts elicited no evidence of toxic products. In vivo tests on hard and soft tissues resulted in biocompatibility with zirconium-based implant materials.[18],[19],[20] Several factors such as surface energy, surface topography, and chemical composition of an implant surface play a vital role in biofilm formation on dental implants.[9],[10],[13-18]

Both titanium and zirconium are hydrophobic in nature. Gram-positive bacteria possess hydrophobic features owing to a thick peptidoglycan layer compared with that of gram-negative bacteria. Thus, gram-positive bacteria get attracted towards implant surfaces, whereas this is not seen in the case of gram-negative bacteria. However, no significant bacterial adhesion is reported for both materials in microbiological studies. The electrical properties of titanium are different from zirconium. Titanium is a semi-conductor as a result of the bioactive dioxide layer whereas zirconium does not conduct electricity. Although these materials are hydrophobic, due to the electrical conductivity, plaque accumulation is more on titanium surfaces than zirconium. Albumin, a salivary protein, is adsorbed onto titanium surfaces. The positively charged calcium ions get attracted towards the negatively charged titanium surface, resulting in adsorption via calcium bridging. The divalent calcium ions bridge the titanium and bacterial surfaces. Streptococcus mutans and Fusobacterium nucleatum species possess a similar binding element and attach to the other surface of the calcium ion.[15],[20]

Surface roughness is directly proportional to bacterial aggregation. As the roughness increases, more surface area is available for the bacteria to hide and proliferate.[10],[21] Abutment surface roughness causes increased supra mucosal plaque accumulation. Biofilm formation as a result of roughness was observed in the submucosal areas, indicating the need for better oral hygiene to avoid bacterial aggregation.[22] A threshold roughness value lesser than 0.2 µm is preferred for an implant surface and other dental biomaterials to lower biofilm formation and related infections.[10]

Bacterial surface consists of complex molecules such as lipopolysaccharides with an anionic cell wall. Surfaces with polar and nonpolar properties can electrostatically attract different bacterial species. Due to the presence of saliva in the oral environment, the surface wettability of both titanium and zirconium-based implants did not contribute to biofilm formation.[23],[24]

The biofilm formed on the abutment surface of titanium and zirconium implants was different from that seen on a natural tooth. A monospecies biofilm of Provetella gingivalis was observed on the implant abutment surface, which can be removed during ultrasonic scaling. Studies report that the bacterial cell number and density were lesser in zirconium-based implants than in titanium-based implants.[24]

Monospecies biofilm of C. albicans also alters the morphological, physical, and chemical properties of both the implant and prostheses, thereby increasing the risk of complications. The biofilm formed on titanium, zirconium and cobalt-chromium materials used in the manufacture of abutments and prostheses showed no major differences, with the density of the biofilm being lesser than that in resins. Hence it is important to avoid using resins in the subgingival area of an implant prosthesis along with limiting the materials used for the fabrication of implants to a combination of cobalt-chromium alloy/ceramic or titanium/ceramic.[25]

Polyetheretherketone (PEEK) is a polymer that is widely used as a biomaterial in orthopedic and dental rehabilitation procedures due to its favorable biomechanical properties. However these materials are not exempted from bacterial adhesion and biofilm formation. Several surface characteristics lead to biofilm formation on the surface of PEEK. Streptococcus sanguinis showed biofilm formation on the roughened PEEK surface within 72h. Similar results were observed for S. oralis, Enterococcus faecalis, and S. gordonii. A study conducted by Barkarmo et al.[26] suggests that PEEK surfaces are more susceptible to bacterial adhesion than titanium and its alloys if sandblasted. Plasma sputtering the surface of PEEK with silver nanoparticles manifested activity against gram-negative  Escherichia More Details coli and gram-positive Staphylococcus aureus. PEEK is a modified biomaterial with an antibiotic and functional peptide nanoparticle coating. This material shows minimal adhesion and growth of Pseudomonas aeruginosa and S. epidermidis as compared with conventional PEEK material. This indicates that both gram-positive and gram-negative bacterial adhesion is the lowest on rough-surfaced PEEK.[27]

Bioactive glass (BAG) is a biomaterial that functions by activating immune cells and various proteins of the body. This property makes BAG a versatile material in dentistry. It is used as a coating on dental implants, as a dental restorative material, mineralizing agent, endodontic material, and as a soft-tissue restorative material in orthopedics. It comprises of various compounds like sodium oxide (Na2O), calcium oxide (CaO), phosphorus pentoxide (P2O5), calcium fluoride (CaF2), and boron oxide (B2O3). BAG expresses broad-spectrum antimicrobial activity. Staphylococcus aureus is the most common bacterial strain found in the biofilm of this material. BAG increases the pH and osmolarity, leading to an environment that is not suitable for bacterial adhesion and biofilm formation. Particle size also influences the antimicrobial property by increasing the surface area with smaller particle sizes. Alkali free BAG doped with zinc oxide, strontium oxide, and hydroxyapatite enhances the antimicrobial properties of this material.[28]

Biofilm-related infections

Biofilms enable the survival of microorganisms in the human body. Research has shown how a biofilm phenotype influences the clinical outcome of an infected individual. Thus, biofilms perfectly correlate with the disease. Although biofilms may be important as a virulence factor in some clinical scenarios, microorganisms can still cause infections in the absence of a biofilm.[9] It is obvious that if the infection develops 3–24 months after surgery, it is not due to contamination at the time of surgery; instead, it may be due to less virulent organisms, hematogenous infection, or an indolent infection acquired during surgery.[29] The bacteria accumulated in biofilms give rise to unconquerable difficulties in the treatment of infections. It is difficult to assess the nature and status of the infection using conventional culture techniques. Therefore, DNA-based molecular methods have been developed to provide rapid identification of all microbial pathogens in a biofilm.[30]

Control of biofilms

Development of infection-resistant implant biomaterials

A biomaterial surface can be modified to reduce bacterial adhesion and hence lessen the chances of biofilm formation. Different methods can be developed for modifying the biomaterial surface. Anti-adhesive materials can be added on the implant biomaterial surface to reduce the level of bacterial adhesion. Doping the implant surface with antimicrobial compounds can destroy the bacteria adhered to the surface. A more effective method can be developed by incorporating both anti-adhesive and antimicrobial compounds together as it not only lessens the adhesion of bacteria to the implant surface but also helps deteriorate any bacteria adsorbed. Super coatings can be introduced that help in bone formation along with anti-adhesive and antibacterial properties. Researchers have attempted to improve the functional condition of implants by changing their chemical composition, which does not affect the adhesion, proliferation, and differentiation of osteoblasts.[31] Moreover, energy-dispersive X-ray spectroscopy confirmed that zirconium, silicon, and fluorine sandblasted onto the surface of a titanium alloy can have a direct effect on the antibacterial activity.[32]

Antibiotic-loaded implant doping

Antibiotics are loaded onto implant surfaces based on the adsorption characteristics of molecules conferring hydrophilic properties to the biomaterial surface. Thus, loading suitable antibiotics that develop a film on the implant can compete with the interaction between the bacteria and host matrix proteins.

Heparin possesses strong hydrophilic properties that can hamper the adhesion of bacterial cells. It forms a hydrated layer between the bacteria and biomaterial surface, thus preventing adhesion. Heparin has a strong inhibitory action against S. epidermidis. A coating of hydrophilic polyethylene glycol or polyethylene oxide on the surface of an implant can also prevent bacterial adhesion to the implant.[4]

Local delivery of antimicrobial agents through carrier biomaterials can be used to avoid the risk of developing antibiotic resistance after a certain period in the case of antibiotic-loaded implants. A promising biopolymer and natural cationic polysaccharide, chitosan, can be used as an antibacterial and antimicrobial agent. Chitosan-lauric acid is used for surface functionalization of titanium substrates. The chitosan-functionalized titanium promotes osteoblast cell adhesion, cell viability, intracellular alkaline phosphatase activity, and mineralization of osteoblasts. This is effective against S. aureus and P. aeruginosa.[7],[29]

A multilayer of antibiotics, heparin, and chitosan can be assembled to obtain an anti-adhesive and antibacterial biomaterial. This multilayer develops an anti-infective coating. Different biomaterials such as resin beads, gold surfaces, polymer brushes, and block copolymers can be used as surface supporters for functionalizing cationic antimicrobial peptides,[4],[29] an innovative osseointegrating antibacterial biomimetic coating on titanium obtained by anodic spark deposition treatment. It forms a chemically and morphologically modified titanium oxide layer enriched with strong antibacterial elements like calcium, silicon, phosphorus, and silver.[4] Recently, the antibiofilm activity of nitric oxide-releasing hyperbranched polymers against in vitro multispecies subgingival biofilms (cultured for seventeen days) as a function of nitrous payload and polymer concentration (4–16mg/mL) were evaluated, and it was concluded that nitric oxide has potential therapeutic utility for treating multispecies dental biofilms.[33]

An in vitro study documented that antibacterial activity and cytotoxicity of an implant coated with minocycline could be controlled for up to seven days, which was a crucial period after implant placement, along with the inhibition of P. gingivalis, and was nontoxic to osteoblasts. Hence, this coating strategy serves as a boon for controlling biofilms in implant therapy.[34]

Graphene and its derivatives such as graphene oxide (GO) and reduced graphene oxides (RGO) manifest biocompatibility and antibacterial activity. GO is hydrophilic due to the presence of oxygen groups in it. Therefore, the cell protein adsorption, cell adhesion and proliferation are improved with GO coatings compared to RGO and pristine, hydrophobic graphene coatings. Graphene based coatings show low friction, they are self-lubricating, bioactive and antibacterial. Several studies support the broad spectrum of antibacterial activity of graphene-based coatings; hence, these coatings are applied on Titanium and its alloys, stainless steel and polymeric materials to inhibit biofilm formation.[35],[36]


  Conclusion Top


New strategies should be followed to control biofilm-mediated implant infections. Rapid identification of bacterial species within the biofilm is done by molecular testing and mass spectrometry, instead of traditional biochemical analysis. Highly sensitive and specific biochemical and hematological markers are studied for the identification and treatment of biofilm-mediated infectious diseases. C-reactive protein, erythrocyte sedimentation rate, white blood cells, and leukocyte esterase are the biomarkers studied for identifying the sensitivity of the bacterial biofilm.[7] Clinicians should extensively adopt newer techniques to deal with biofilm-mediated therapeutic challenges.

Multiple microorganisms present in biofilms coordinate and survive via quorum sensing, thus making biofilms resistant to many antibiotics. Quorum quenching lowers quorum sensing; as a result, the cell-to-cell signaling and cell density of the biofilm decreases.[30] Quorum quenching could be an alternative strategy to combat bacterial infections as it lowers the development of multidrug-resistant pathogens. Rapid development and dissemination of antibiotic resistance have led to the emergence of extensively drug-resistant and totally drug-resistant strains, collectively known as superbugs. Anti-quorum sensing activities are safer as they do not kill bacteria, and the chances of developing resistance is low.[30],[37]

Acknowledgement

Not applicable.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Authors’ contributions

TT and MS: concept and design of study, drafting, and revision. MM and KR: acquisition of data, analysis, and interpretation. AIN: acquisition of data, interpretation, and drafting. KG: concept design, acquisition and interpretation of data, drafting, and revision. Finally, all authors had given approval of the version to be published.

Data availability statement

Within this manuscript, the presented data set was retrieved from 33 original articles. The data is already present in these articles.



[38]

 
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    Figures

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