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In the modern era, the expanding demand for implants has transformed the healthcare system by restoring and enhancing the function of various biological structures, thereby increasing the patients’ quality of life. These include urinary catheters, dental, orthopedic, cardiovascular implants, and sutures designed to perform various functions. However, these devices are more prone to microbial attack, contributing to biofilm formation mainly caused by multidrug-resistant ESKAPE pathogens, thereby increasing the risk of implant-associated infections and implant failure. This review summarizes the diverse array of implants available on the market and their associated infections caused by biofilm-producing pathogens, with a particular emphasis on the ESKAPE pathogen. Specific keywords were used to conduct a literature review using Google Scholar, Web of Science, PubMed, and Scopus databases. The data were then screened and integrated to explore the underlying principles of biofilm formation, its consequences, diagnostic approaches, and therapeutic studies. Currently, various methods are employed to diagnose these infections, including culture-based methods (tissue swab, culture, sonication) and non-culture methods (Dithiothreitol, XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide), Resazurin, BioTimer assays, and PCR). However, these studies indicate an increased difficulty in detecting infections caused by ESKAPE pathogens due to biofilm formation, highlighting the need for developing novel strategies. The recent advancements in the development of antimicrobial coatings, implant surface modifications, phage therapy, nanoparticles, antimicrobial peptides, and quorum-sensing inhibitors have shown promise in controlling these infections. Thus, these findings underscore the importance of research on innovative approaches and the development of infection-resistant implants, thereby reducing the clinical burden and improving patient outcomes.
IntroductionThe introduction of implants has enhanced the efficiency and functionality of organs such as the heart, bones, and teeth. The primary function of these devices is to replace damaged parts, restore appearance, reduce discomfort, and improve the performance of various biological structures. Today, numerous types of implants are available on the market, including stents, urinary devices, pacemakers, sutures, contact lenses, dental implants, endotracheal tubes, fracture fixation devices, and others, where these are used for various medical uses such as being inserted into the urethra, jawbone, muscles, bones, and other body parts. Their production relies heavily on biomaterials, including metals, alloys, ceramics, polymers, and composites, which are selected for their mechanical strength, durability, and biocompatibility (Teo et al., 2016; Narayana and Srihari, 2019; Ramezani and Ripin, 2023).
Apart from their medicinal benefits, they provide an environment that favors the growth and colonization of numerous bacteria by interacting with the implant surface, which can lead to implant-associated infections (IAI). The colonization of bacteria such as Staphylococcus sp., Streptococcus sp., Corynebacterium sp., Cutibacterium acnes, Escherichia coli, Pseudomonas sp., Klebsiella pneumoniae, Providencia stuartii, and others on the surfaces of implanted medical devices made of inert materials and polymers is a significant contributing factor to IAI (Nikolaev and Plakunov, 2007; Dongari-Bagtzoglou, 2008; Kandi and Vadakedath, 2020). These infections are due to the formation of biofilms on implant surfaces, structured groups of sessile cells enclosed within an extracellular polymeric matrix that provides protection against antimicrobial agents, nutrient limitations, and various immune responses. However, quorum sensing plays a vital role in regulating the formation of biofilm by enabling bacteria to communicate with each other and to coordinate their response to external stimuli (Whitchurch et al., 2002; Lu et al., 2022; Tiwari, 2023).
The National Institutes of Health reports have indicated that up to 80% infections in humans due to microbes arise from biofilm formation, leading to implant infections (Nandakumar et al., 2013; Khatoon et al., 2018; Mishra et al., 2024). The proliferation of multidrug-resistant (MDR) microorganisms, particularly a group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.), drives the formation of bacterial biofilms and the associated infections. Forming biofilms is a key mechanism by which drug-resistant and multidrug-resistant ESKAPE pathogens exhibit antimicrobial resistance. These multidrug-resistant (MDR) pathogens have developed antibiotic resistance, shielding biofilms from antimicrobial agents, leading to persistent infections that are difficult to eradicate. As these biofilms exhibit high collective resistance due to horizontal gene transfer and mutation rates, and are recognized as reservoirs for antibiotic-related genes (Lin et al., 2018; Uruén et al., 2020; Saini et al., 2024). The ESKAPE pathogens are considered the primary contributors to biofilm-associated infections and are responsible for nearly 40% of infections in intensive care units, according to records of the National Healthcare Safety Network (Bennett et al., 2023).
Recent therapeutical approaches such as phage-based therapies, nanomedicine-based interventions, and prophylactic strategies altering the implant surface have helped to address the challenges due to biofilm (Lu et al., 2022). The risks involved with IAI in patients remain, including loss of function, increased susceptibility to infections, tissue damage, and financial burden. Thus, there is a need to develop implants that are effective, biocompatible, infection-resistant, and long-lasting. This review focuses on implant types, biofilm formation on implants by ESKAPE pathogens, implant-associated infections, and existing methods for treating and preventing IAI, highlighting the need for developing biofilm-resistant implants.
The historical progression and growth of implant technologyDating back to ancient civilizations, implants were used to enhance the function of various body parts. Archaeological evidence indicates that, the Mayan population in the 3rd century AD employed bow drills to fill up tooth gaps and used carved stones to replace the lost teeth. The Phoenicians in the 3rd century AD and the Etruscans in the 5th century AD utilized gold wire and bands, respectively, to restore the functionality of the oral cavity. Additionally, the ancient Egyptians around 2500 BC used gold wire to improve the stability of teeth (Pasqualini and Pasqualini, 2009; Abraham, 2014). Metal-based dental implants were developed during World War II for dental restorative purposes and gained wider acceptance, leading to the establishment of modern implants. The first use of titanium dental implants was reported in 1965, which were used to replace lost teeth. Later, in 1992, ceramic implants were introduced, which demonstrated enhanced osseointegration capabilities in patients (Gaviria et al., 2014). The remarkable progress in biomedical technology has enabled the introduction of a diverse array of implant materials in the healthcare market, which have consequently enhanced the quality of life for patients.
Typologies of medical implantsImplants are becoming increasingly valuable day by day due to their beneficial impact on the physiological functions in the patient. As a result, there are wide variety of implants being used in the medical field, including contact lenses, urinary catheters, sutures, stents, pacemakers, fracture fixation devices, dental implants, hip implants, breast implants, and endotracheal implants, which are inserted into various body parts, such as the eyes, urethra, skin, blood vessels, bones, and teeth. Therefore, numerous biomaterials like polymers, steel wire, silicone, latex, zirconia, titanium, and cobalt-chromium alloys are used for development of these implants (Narayana and Srihari, 2019; Ramezani and Ripin, 2023; AD et al., 2024). The widespread adoption of implants has revolutionized the medical field due to their improved performance. Table 1 summarizes the various biomaterials used in the production of medical implants, along with their respective benefits and applications.
S.NOImplantsTargetMaterialsUsesBenefitsReferences1Dental implantsJawboneTitanium, cobalt-chromium alloy, alumina, zirconia, stainless steel, bioglassReconstruct teeth,Enhance osseo-integration(Narayana and Srihari, 2019; Saha and Roy, 2023)2Urinary catheterUrethraLatex, silicone, nylon, Polyethylene terephthalateHelps to empty the bladder, prevents leakage of urineMinimize the risk of infection and kidney damage(Feneley et al., 2015; Narayana and Srihari, 2019)3Contact lensesEyesPolymethylmethacrylate, polyhydroethylmethacrylate, siliconeVision corrections, appearance of eyes can be changedFix eye problems, improved vision(Narayana and Srihari, 2019; Dosler et al., 2020)4Breast implantsBreastSiliconeAugmentation and Reconstruction of breastEnhance the size, correction of asymmetries(del Pozo and Auba, 2015; Narayana and Srihari, 2019)5SuturesSkin, tissues, organsNylon, silk, polydioxanone, steel wire, polypropyleneHelp to close wound cuts andBiomaterials used in various implants and their corresponding targets.
The table provides a structured overview of the diverse range of implantable devices currently available, emphasizing their role in enhancing patient quality of life. It details the target anatomical sites, the materials used in their construction, and the intended applications and benefits associated with each implant type.
The Food and Drug Administration (FDA) classifies medical implants into three primary categories based on safety considerations and regulatory oversight. Class I devices, such as elastic bandages and handheld surgical instruments, are subject to general controls, including registration, manufacturing, labelling, and provision of FDA information, without requiring rigorous scientific evaluation. Class II devices, predominantly utilized in orthopedic procedures, sutures, surgical drapes, and infusion pumps, exhibit more than minimal potential for harm and thus require specialized controls. Finally, Class III devices, which includes high-risk items such as intramedullary nails, cannulated screws, plates, external fixators, pedicle screws, and rods, necessitate both general and special controls to ensure their safety and efficacy (van Eck et al., 2009). According to reports from the FDA and estimates from Medtech Europe, there are more than 500,000 types of medical implants available worldwide. Table 2 is the representation of the implants, which are grouped into transient, permanent, intracorporeal (intravascular and extravascular), and extracorporeal implants based on their level of intrusiveness into the body, integration into different anatomical structures, and duration of use (Arciola et al., 2018).
ClassClassificationExampleReferenceTransientUrinary catheters
Biodegradable implant (Cardiac Pacing Devices, Scaffolds, Drug delivery implants, Orthopedic implants)
(Rüegg et al., 2019; Xia et al., 2025)PermanentPacemakers(Joung, 2013)Intracorporea Intravascular(Michael and Timmons, 2010; Oliva et al., 2021; Straube et al., 2022)Intracorporeal ExtravascularImplantable cardioverter-defibrillators (ICDs)
Intracorporeal pressure measurement devices
Orthopedic Implants (hip, knee prostheses)
(Michael and Timmons, 2010; Oliva et al., 2021; Hashmi et al., 2023)ExtracorporealExtracorporeal oxygenators(Lim, 2006; Berthiaume et al., 2016)Overview of biomedical implants and their examples.
This table categorizes biomedical implants into various classifications based on their long-term or short-term nature, as well as their interaction within or outside the body, with corresponding examples.
Infections stemming from implanted medical devicesThe adhesion and accumulation of microorganisms especially on the surfaces of biomaterials used in medical implants, including stainless steel, nylon, polymers, silicone, chromium, titanium alloy, and various other alloys are more susceptible to biofilm formation. This susceptibility to biofilm formation is attributed to the presence of diverse microorganisms, particularly the ESKAPE pathogens (Mukherjee et al., 2023).
A higher percentage of hospital-related complications and the mortality due to infection is mainly observed due to nosocomial infections, which are infections that arise due to close contact with infected patients and their environment (Hocevar et al., 2012). A significant proportion, approximately 80%, of known pathogenic microorganisms have been associated with infections related to a diverse array of implanted medical devices, including intravenous and urinary catheters, joint prostheses, penile implants, contact lenses, fracture fixation devices, cardiovascular and biliary stents, and other such implanted medical technologies (Ruellan et al., 2010; Ramasamy and Lee, 2016). Biofilms on medical devices facilitate the transmission of pathogens and contribute to the development of infections. Table 3 outlines IAI resulting from biofilm formation and its associated consequences. Microorganisms such as S. aureus and Staphylococcus epidermidis are recognized as the key contributors to healthcare-associated infections, causing a significant proportion of infections associated with various medical implants. These bacteria account for 31-52% of infections associated with orthopedic prosthetics, 40-50% of infections related to prosthetic heart valves, 50-70% of catheter-associated biofilm infections, and 87% of systemic infections (Nikoomanzari et al., 2022).
S.NOImplantsInfection/diseaseSide effectsReferences1Dental implantPeri-implant mucositis, peri-implantitisDental implant failure, tissue damage, increased inflammation(Dhir, 2013; Barão et al., 2022)2SuturesSurgical site infections, chronic wound infectionsProlonged hospitalization, affect tissue, death, suture dehiscence(Hrynyshyn et al., 2022)3Urinary implantsCatheter-associated urinary tract infectionsIncreased risk of recurrent infections, biofilm upregulate toxins, cause tissue damage(Lila et al., 2023)4Fracture fixation devicesSurgical site infectionInfection to soft and bone tissue(Kanakaris and Giannoudis, 2021)5Breast implantsBreast implant illness,Implant-associated infection caused by biofilm and its clinical morbidities.
Implants are widely used to enhance patient health and quality of life; however, they can also serve as ideal surfaces for bacterial colonization. This often results in the formation of resilient biofilms, which are a major cause of implant-associated infections. The table outlines various implant types, the specific infections commonly linked to biofilm formation on their surfaces, and the associated adverse effects on patient health, such as inflammation, tissue damage, and implant failure.
Urinary catheters: The colonization of bacteria on the periurethral skin facilitates in migration of bacteria into the bladder and causes biofilm on indwelling catheters (Stickler, 2008). Bacteria raise urine pH by promoting the development of struvite biofilms within catheters (Neethirajan et al., 2014).
Orthopedic implants: About 15% of hip implant failures related to infections require revision surgery to replace the implant (Bozic et al., 2009), causing inflammation and tissue damage. Techniques, including the modification of the surface textures of orthopedic implants through sintering (Gahlert et al., 2007), sandblasting (Grassi et al., 2007), plasma spraying can enhance their resistance to biofilm formation.
Joint prostheses: Implant failure owing to aseptic loosening is increasingly associated with underlying biofilm-driven infections. Infections of prosthetic joints by S. epidermidis or C. acnes can lead to severe complications and heightened mortality rates in patients following joint replacement procedures (del Pozo and Auba, 2015).
Medical implants in India: usage trends and infectionsIn India, the use of implants has increased significantly due to population aging, rising chronic infections, and emerging technologies. Chronic infections such as diabetes, cardiovascular disease, and musculoskeletal disorders elevated the use of implants, including pacemakers, stents, and joint replacements, in the aging population. According to IMARC Group reports, the Indian implants market is valued at USD 115.4 billion in 2024 and is expected to reach USD 189.6 billion by 2033. Analyses of the Indian implant market indicate that orthopedic conditions such as osteoarthritis, fractures, and degenerative bone diseases are highly prevalent, contributing to increased demand for orthopedic implants (IMARC, 2024). The Reed Intelligence reports indicate that the Indian orthopedic implants market reached USD 1,018.13 million in 2024 and is projected to reach USD 1,629.47 million by 2033 (Reed Intelligence, 2024). In India, implant-associated infection affects nearly 6% of orthopedic implants, leading to economic loss to the patient (Sarkar et al., 2024). Orthopedic IAI are commonly due to S. aureus, and other risk factors include obesity, smoking, and longer surgery duration, with a reported prevalence of 25.7% (Kiran et al., 2023). Management of orthopedic IAI is challenging, as inappropriate antibiotic use can contribute to antimicrobial resistance and delay treatment outcomes, thereby resulting in prolonged hospitalization, increased morbidity, and an economic burden in patients (Shakthi and Venkatesha, 2023). Surgical site infection rates in India range from 1.6% to 38% by area, with S. aureus as the predominant pathogen. In this study, the incidence of infection was 7.6%, which is low compared to India’s highest reported figures but remained higher than that reported in high- and middle-income countries (Skender et al., 2022).
A recent study reported that the incidence of central line-associated bloodstream infections (CLABSI) was higher than in developed countries, and the associated pathogens were predominantly multidrug-resistant, such as Acinetobacter sp. (22%), followed by K. pneumoniae (16%) and Enterobacter aerogenes (16%) (Maqbool and Sharma, 2023). In India, almost 37,000 cardiac implanted electronic devices (CIEDs) were sold during the survey year, according to Eucomed data. This survey also highlights a marked gender imbalance, a gap that is even more pronounced for costly devices such as Implantable Cardioverter-Defibrillator (ICD) and cardiac resynchronization therapy (CRT), and where men receive the majority of CIED implants. Despite indications that women with dilated cardiomyopathy frequently benefit more from CRT, women are particularly disadvantaged in getting these treatments in a system with little government financing and insurance coverage (Shenthar et al., 2016).
Microorganisms in biofilm establishmentBiofilm on implants is formed by various bacteria, including both Gram-positive species such as Enterococcus faecalis, S. aureus, S. epidermidis, and Streptococcus viridans, as well as Gram-negative species like E. coli, K. pneumoniae, Proteus mirabilis, and P. aeruginosa. The predominant organisms involved in biofilm formation are catalogued in Table 4. These pathogens can attach and form biofilms at the implantation site and on the implant device, leading to adverse outcomes such as implant failure, tissue damage, and associated infections (Veerachamy et al., 2014). Besides the bacteria previously mentioned, the ESKAPE pathogens has emerged as a major concern, causing persistent infections and leading to higher mortality rates (Tiwari, 2023).
S.NOImplantsMicroorganismsReferences1Dental implantS. viridans, Streptococcus mitis, Streptococcus oralis, Actinomyces sp., Strptococcus mutans, Streptococcus sobrinus, Fusobacterium nucleatum, P. gingivalis, P. intermedia(Dhir, 2013)2SuturesS. aureus, Enterococcus sp., E. coli, Streptococcus pyogenes(Hrynyshyn et al., 2022)3Urinary implantsE. faecalis, P. aeruginosa, E. coli, P. mirabilis, S. aureus, K. pneumoniae, S. epidermidis, A. baumannii(Tenke et al., 2012; Lila et al., 2023)4Fracture fixation devicesS. aureus, S. epidermidis, coagulase-negativeStaphylococcus, S. viridans, E. faecalis, E. coli, K. pneumoniae, C. acnes, Peptostreptococci, P. mirabilis, A. baumanii, and P. aeruginosa.(Kanakaris and Giannoudis, 2021)5Breast implantsP. acnes, S. epidermidis(Lee et al., 2020)6Contact lensesP. aeruginosa, Serratia sp., S. aureus,(Bispo et al., 2015)7Mechanical heart valveStreptococci,Major biofilm forming microbial species.
This table provides an overview of key microbial species involved in biofilm formation, particularly on biomedical implants. These microbes have the potential to adhere to various surfaces, construct complex communities, and thereby develop resistance mechanisms against both antibiotics and the host's immune defenses.
Biofilm structure and compositionThe microbial colonization on the implant surface forms a biofilm composed of a diverse group of microorganisms capable of producing extracellular polymeric substances (EPS) that protect the bacterial community from external forces. Biofilm is primarily made up of 90% water and 10% microbial mass. The biofilm matrix is composed of polysaccharides (EPS), which constitute 50-90% of the total organic components (Donlan, 2002; Abdelaziz et al., 2025) as illustrated in Figure 1. This matrix forms a thick, mesh-like structure, where the polysaccharide sequences with hydroxyl groups interact with each other, enhancing their mechanical strength. Calcium (Ca2+) and magnesium (Mg2+) ions present in the biofilm matrix support the cross-bridge formation, contributing to the polymer stabilization, and also facilitates the maturation and formation of biofilms to a thickness of around 300 µm (Sharma et al., 2023).
A schematic diagram illustrating the core components and structural organization of bacterial biofilms. This illustration represents a fully developed biofilm adhered to an implant surface, highlighting its structural components, including polysaccharides, DNA, RNA, lipids, water channels, quorum sensing molecules, proteins, and bacterial cells, all integrated within an extracellular polymeric substance matrix.
The adherence of microorganisms to material surfacesBacterial adhesion is the process by which free-floating cells attach to the conditioning layer of implants with the help of adhesins (Khatoon et al., 2018; Filipović et al., 2020). Therefore, these bacteria utilizes flagella, pili, or various physical forces, such as steric, van der Waals, and hydrophobic forces, as well as protein adhesion, enhancing the attachment, as illustrated in Figure 2. Bacterial adhesion to a surface involves two phases mainly: an initial, immediate, and reversible physical phase, followed by a time-dependent, irreversible molecular and cellular phase (Ribeiro et al., 2012; Zhao et al., 2023). The factors influencing bacterial adhesion are outlined in Table 5.
The image illustrates the visualization of bacteria adhering to the surface of an implant. The initial phase of biofilm development involves the adherence of planktonic cells to the implant surface. This adhesion process is a pivotal factor in the development of implant-associated infections, facilitated by structures like pili and flagella, along with forces such as hydrophobic, steric, van der Waals, and electrostatic interactions.
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