Advances in Material Modification with Smart Functional Polymers for Combating Biofilms in Biomedical Applications
Abstract
:1. Introduction
2. Relevance of Biofilms in the Biomedical Field
2.1. Biofilm Conceptualization
2.2. Statistics about Biofilms in Disease
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- Most chronic wounds have a biofilm (78.2%). In 2017, healthcare spent 7800 billion dollars on injuries, with 281 billion dollars linked to biofilms.
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- Biofilms impact the lung and digestive systems of cystic fibrosis patients. They are resilient to antibiotics and contribute significantly to the economic impact of CF, with global costs reaching 7509 million dollars annually.
- ◦
- Infective endocarditis is a serious condition caused by bacteria or fungi. Biofilms are a major cause of the disease. The incidence of infective endocarditis is increasing, with an estimated annual economic impact of $16 billion globally.
- ◦
- Bacterial biofilm infections cause chronic sinusitis and can be treated with antibiotics or surfactants. The global cost of this condition is estimated to be $24.4 billion.
- ◦
- Biofilms are a recurring issue in catheter-associated infections. The cost of diseases due to central venous catheters is estimated at 11.5 billion dollars globally, while catheter-associated urinary tract infections affect around 150 million people annually, costing $1 billion worldwide.
- ◦
- Biofilm infections in ophthalmology can occur in the eye, eyelids and as a result of contact lenses or artificial lenses introduced during cataract surgery. Eye conditions associated with biofilms cost around $759.3 million annually globally.
- ◦
- Although pacemaker and defibrillator insertion are generally considered low-risk, biofilm infections affect 1–3% of patients within 12 months, leading to antibiotic treatment and often device replacement. Global spending on biofilm-related illnesses in pacemakers and defibrillators is $220 million annually.
- ◦
- Endotracheal tubes on ventilated patients can develop bacterial biofilms within 24 h of intubation, increasing the risk of ventilator-associated pneumonia. 35% of ICU beds in the USA are occupied by mechanically ventilated patients, costing an estimated $920 million globally annually.
- ◦
- Prosthetic joint surfaces can get infected with biofilms, leading to antibiotic failure and possibly surgery. There are few alternatives to surgery, and the cost of revision surgery due to biofilm infections is $7849 million globally annually.
2.3. Common Bacteria Forming Biofilms and Medical Devices
3. Molecular and Biological Bases of Biofilm Formation
4. Smart, Functional Polymers
4.1. Classification of Smart Polymers
4.2. Main Applications of Smart Polymers
5. Current Advances in the Use of Smart Polymers for Combating Biofilms
5.1. Antimicrobial and Antibiofilm Activities of Smart Polymers
5.2. Combination of Smart Polymers and Antimicrobial Agents
5.3. Smart Polymer Nanomaterials as Antimicrobial and Antibiofilm Agents
5.4. Stimuli-Responsive-Smart Polymers as Anti-Biofilm Agents
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Microorganism | Medical Device | Infections and Diseases | Reference |
---|---|---|---|
Staphylococcus aureus | Catheters | Osteomyelitis, soft tissue and skin infections, excessive inflammation, delayed wound healing, and re-epithelialization. | [24] |
Escherichia coli | Urinary catheters | Gastroenteritis, sepsis, neonatal meningitis, and urinary tract infections. | [25] |
Pseudomonas aeruginosa | Prothesis or orthopedic devices, heart valve infections, central catheters, endotracheal tubes | Burn infections, wound infections, pneumonia, and bloodstream infections. | [26] |
Staphylococcus epidermidis | Artificial heart valves and prosthetic or orthopedic device | Endocarditis, bloodstream, and central catheter infections. | [27] |
Enterococcus faecalis | Urinary catheters | Infections in the urinary tract, bacteremia, and endocarditis | [28] |
Candida albicans | Catheters | Yeast infections, thrush, systemic candidiasis | [29] |
Klebsiella pneumoniae | Ventilators | Pneumonia, urinary tract infections, bacteremia, and bloodstream infections. | [30] |
Microorganism | Mechanism | Reference |
---|---|---|
Candida albicans | Aggregation in the form of yeast. Al' glycoprotein family (Als1-7, 9) regulates adhesion to host cells or extracellular matrix proteins. Als3, Bgl2, Tec1p, Bcr1 zinc finger protein, RTA3, Hwp1, MAPK protein kinase, Sphingolipids with sterols and glycerophospholipids, as well as B-glucanase mannoprotein and target/encoding genes, promotes biofilm formation playing a pivotal role in the hyphal building. Ywpi deletion mutants adhere to polystyrene. Sfpt1 gene deletion enhances cell adhesion. Cells propagate, and germ tubes form to yield hyphae; mycelium growth causes colony fusing to form a monolayer with an extracellular matrix composed of polysaccharides and extracellular DNA (eDNA) that protects the cell inside the biofilm. eDNA induces cell lysis and QS. | [33] |
Streptomyces coelicolor | A suitable source of nutrients y sensed by spores, they germinate under aerial growth, forming vegetative hydrophilic mycelia, which transitions to aerial hydrophobic hyphae with the extracellular proteinaceous surface formed by chaplins (ChpA-H) and rodlins (RdlA and RdlB). Fimbria structures play the same role in liquid-static cultures. CslA, SapB, and coding genes are also involved in attachment. GBLs, MMFs, Factor A, Factor-I, IM-s, VB, and PI factor act as QA molecules. | [34] |
Staphylococci (S. aureus, S. epidermidis) | They attach to biotic surfaces containing fibrinogen, fibronectin, vitronectin, and collagen through cell wall-anchored proteins (FnBPA, FnBPB, ClfA-B, SdrC-H, and Brp) or to abiotic surfaces through hydrophobic and electrostatic interactions through extracellular glycopolymers (teichoic acids), autolytic enzymes (AtlA and AtlE) which are vital in the release of eDNA, and accumulation-associated protein (Aap or SasG) through its N-terminal A domain. | [31] |
Pseudomas aeruginosa | Flagella, type IV pili, Cup fimbria, eDNA, and Psl polysaccharide initiate adhesion. Adhesin CdrA binds to Psl for aggregation. Cationic e-DNA cross-linking Pel and alginate exopolysaccharide enables biofilm formation, with lectins LecA/LecB and functional amyloid Fap. All are regulated by c-di-GMP, which also negatively regulates motility. LasI/LasR and Rh1I/Rh1R QS proteins act upon HSLs, and the 2-heptyl-3-hydroxy-4-quinolone system regulates rhamnolipid production for biofilm resistance to host immune response. | [35] |
Escherichia coli | For initial attachment, Flagella and proteinaceous curly fibers (CsgA and CsgB) are required. Type 1 pili (FimA, FimH) and P pili (PapA, PapG). are central for irreversible attachment to mannose residues on cells. Cellulose, PGA eDNA, and colanic acid compose the biofilm matrix. Their production is regulated by c-di-GMP (primarily controlled by DgcE), negatively regulating motility. QS employs a furanosyl borate diester (AI-2) system. | [35] |
Acinetobacter baumannii | These bacteria lack flagella. Csu pili and OmpA outer membrane protein mediate biotic and abiotic surface adhesion. Bap keeps the structure of the biofilm matrix. Synthesized alginate and PNAG exopolysaccharides together with eDNA ate biofilm matrix components. A Fe3+-induced AHL/AbaI/AbaR-based QS system increases the expression of Csu pili. | [35] |
Polymer | Biomedical device | Microorganisms | Results | References |
---|---|---|---|---|
Poly-N-vinylpyrrolidone (PNVP) coating on polyurethane | Central venous catheter | S. aureus | Impeded biofilm formation for at least 48 h. | [55] |
S. epidermidis | ||||
Polypropylene (PP) film crosslinked with PNIPAAm (PP-PNIPAAm) or PAAc (PP-PAAc) | Tentative components in prostheses and catheters | S. aureus (MRSA) | All vancomycin-loaded modified films showed significant anti-biofilm effects. The thinnest grafting layer of PP-PAAc had the greater reduction (91.7%) | [56] |
Hydrogel of poly-2-hydroxyethyl methacrylate (pHEMA) | Intraocular lens surface | S. epidermidis | The antimicrobial activity of norfloxacin was improved to eradicate both planktonic and biofilm forms. | [57] |
Polyurethane (PU) with soft domain constituted by one of the following macrodiols: polypropylene oxide (PPO), polycaprolactide (PCL), and poly-L-lactide (PLA). | Future synthesis/coating of medical devices | S. epidermidis | Best antifouling properties and reduced bacterial adhesiveness by PU-PLA (2 × 102 CFUs/cm2) | [58] |
Hydrogel/silicone | Medical devices | S. aureus | Prevented the development of bacterial resistance during long-term use. | [59] |
Nanostructured-silver-treated polymers | Catheters | S. albus | It prevented the development of bacterial resistance at 99.99% of Pseudomonas aeruginosa and Staphylococcus albus. | [60] |
Endotracheal tubes | P. aeruginosa | |||
Wound dressings | E. coli | |||
Surgical mesh | B. anthracis | |||
Other polymeric fibers | ||||
Poly (N-isopropyl acrylamide) with vancomycin end groups (HB-PNIPAM-van) | Infected dermal tissue model | S. aureus | HB-PNIPAM-van altered the biofilm structure on a surface, inhibiting cell attachment and reducing bacterial load. | [61] |
Polydimethylsiloxane (PDMS) | Implanted medical devices | S. epidermidis | Strong biofilm inhibiting activity of the coatings, decreasing biofilm thickness for untreated and modified coatings. | [62] |
Silicone oil-coated polypropylene (PP) plastic and polystyrene (PS) | Urinometer | E. coli, P. mirabilis | Silicone oil-coated polypropylene plastic surfaces significantly inhibited the formation of Gram-negative and Gram-positive bacteria biofilm. Even without PP, the plastic itself prevented biofilm formation more than PS. | [63] |
Poly-4-hydroxybutyrate (PH4B) | Kinetted polypropylene implants | E. coli | Reduced biofilm formation on P4HB compared with PP flat films. | [64] |
S. aureus | ||||
Smart hydrogel consisted of norspermidine, aminoglycosides, and oxidized polysaccharide | Medical devices | P. aeruginosa | Inhibition of the associated biofilm infections and chronic wound infections in clinics. | [65] |
Multi-layered temperature-responsive polymer brush (MLTRPB) | Orthopedic implants | S. aureus | Antibacterial effect of the MLTRPB coating with more than four layers in vitro and in vivo studies. | [66] |
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Mejía-Manzano, L.A.; Vázquez-Villegas, P.; Prado-Cervantes, L.V.; Franco-Gómez, K.X.; Carbajal-Ocaña, S.; Sotelo-Cortés, D.L.; Atehortúa-Benítez, V.; Delgado-Rodríguez, M.; Membrillo-Hernández, J. Advances in Material Modification with Smart Functional Polymers for Combating Biofilms in Biomedical Applications. Polymers 2023, 15, 3021. https://doi.org/10.3390/polym15143021
Mejía-Manzano LA, Vázquez-Villegas P, Prado-Cervantes LV, Franco-Gómez KX, Carbajal-Ocaña S, Sotelo-Cortés DL, Atehortúa-Benítez V, Delgado-Rodríguez M, Membrillo-Hernández J. Advances in Material Modification with Smart Functional Polymers for Combating Biofilms in Biomedical Applications. Polymers. 2023; 15(14):3021. https://doi.org/10.3390/polym15143021
Chicago/Turabian StyleMejía-Manzano, Luis Alberto, Patricia Vázquez-Villegas, Luis Vicente Prado-Cervantes, Kristeel Ximena Franco-Gómez, Susana Carbajal-Ocaña, Daniela Lizeth Sotelo-Cortés, Valeria Atehortúa-Benítez, Miguel Delgado-Rodríguez, and Jorge Membrillo-Hernández. 2023. "Advances in Material Modification with Smart Functional Polymers for Combating Biofilms in Biomedical Applications" Polymers 15, no. 14: 3021. https://doi.org/10.3390/polym15143021