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Abstract Bacterial biofilms on the surfaces of indwelling biomedical devices can cause long‐term infection and patient morbidity and mortality. Wrinkled surface topographies have previously demonstrated promising antifouling properties. Here we report a bioinspired strategy in which the actuation of silk fibroin produces tunable, wrinkled surface topographies on 2D shape memory polymer (SMP) substrates and investigate the influence of these topographies on biofilm formation. To mimic biofilm‐associated infections related to the geometries of indwelling medical devices, silk wrinkles are produced on complex, 3D SMP architectures, and biofilm formation is evaluated. Using common biofilm‐causing agents, smaller silk wrinkle wavelengths and amplitudes are found to significantly reduce biofilm formation, resulting in primarily isolated, single‐cell bacteria on the 2D wrinkled surfaces. These single‐cell bacteria are nearly completely eradicated by treatment with antibiotics, which are ineffective against control surfaces. Antibiotics are also physically incorporated into the 2D wrinkled surfaces, which resulted in a further significant reduction in bacterial adhesion. Lastly, silk wrinkled topographies are successfully applied on 3D architectures, and the wrinkled surfaces display a significant reduction in biofilm coverage compared to controls. The findings demonstrate the potential for biopolymer wrinkles on biomaterials to be used as antifouling surfaces for biofilm prevention.
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Functionalized Self-Assembled Monolayers: Versatile Strategies to Combat Bacterial Biofilm Formation
Bacterial infections due to biofilms account for up to 80% of bacterial infections in humans. With the increased use of antibiotic treatments, indwelling medical devices, disinfectants, and longer hospital stays, antibiotic resistant infections are sharply increasing. Annual deaths are predicted to outpace cancer and diabetes combined by 2050. In the past two decades, both chemical and physical strategies have arisen to combat biofilm formation on surfaces. One such promising chemical strategy is the formation of a self-assembled monolayer (SAM), due to its small layer thickness, strong covalent bonds, typically facile synthesis, and versatility. With the goal of combating biofilm formation, the SAM could be used to tether an antibacterial agent such as a small-molecule antibiotic, nanoparticle, peptide, or polymer to the surface, and limit the agent’s release into its environment. This review focuses on the use of SAMs to inhibit biofilm formation, both on their own and by covalent grafting of a biocidal agent, with the potential to be used in indwelling medical devices. We conclude with our perspectives on ongoing challenges and future directions for this field.
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- Award ID(s):
- 1919685
- PAR ID:
- 10358041
- Date Published:
- Journal Name:
- Pharmaceutics
- Volume:
- 14
- Issue:
- 8
- ISSN:
- 1999-4923
- Page Range / eLocation ID:
- 1613
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)INTRODUCTION: Orthopedic implants are important therapeutic devices for the management of a wide range of orthopedic conditions. However, bacterial infections of orthopedic implants remain a major problem, and not an uncommon one, leading to an increased rate of osteomyelitis, sepsis, implant failure and dysfunction, etc. Treating these infections is more challenging as the causative organism protects itself by the production of a biofilm over the implant’s surface (1). Infections start by the adhesion and colonization of pathogenic bacteria such as Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), Escherichia coli (E. coli), Methicillin-Resistant Staphylococcus aureus (MRSA), and Multi-Drug Resistant Escherichia coli (MDR E. coli) on the implant’s surfaces. Specifically, Staphylococcus comprises up to two-thirds of all pathogens involved in orthopedic implant infections (2). However, bacterial surface adhesion is a complex process influenced by several factors such as chemical composition, hydrophobicity, magnetization, surface charge, and surface roughness of the implant (3). Considering the intimate association between bacteria and the implant surface, we measured the effect of stainless-steel surface properties on bacterial surface attachment and subsequent formation of biofilms controlling above mentioned factors. METHODS: The prominent bacteria responsible for orthopedic implant infections (SA, SE, E. coli, MRSA, and MDR E. coli) were used in this study. We were able to control the grain size of medical grade 304 and 316L stainless steel without altering their chemical composition (grain size range= 20μm-200nm) (4). Grain size control affected the nano-topography of the material surfaces which was measured by an Atomic Force Microscope (AFM). Grain sizes, such as 0.2, 0.5, 1, 2, 3, 9, and 10 μm, were used both polished and non-polished. All the stainless-steel samples were cleaned by treating with acetone and ethanol under sonication. Triplicates of all polished and non-polished samples with different grain sizes were subjected to magnetization of DM, 0.1T, 0.5T, and 1T, before seeding them with the bacteria. Controls were used in the form of untreated samples. Bacterial were grown in Tryptic Soy Broth (TSB). An actively growing bacterial suspension was seeded onto the stainless-steel discs into 24-well micro-titer plates and kept for incubation. After 24 hours of incubation, the stainless-steel discs were washed with Phosphate Buffer Saline (PBS) to remove the plankton bacteria and allow the sessile bacteria in the biofilm to remain. The degree of development of the bacterial biofilms on the stainless-steel discs were measured using spectrophotometric analysis. For this, the bacterial biofilm was removed from the stainless steel by sonication. The formation of biofilms was also determined by performing a biofilm staining method using Safranin. RESULTS SECTION: AFM results revealed a slight decrease in roughness by decreasing the grain size of the material. Moreover, the samples were segregated into two categories of polished and non-polished samples, in which polishing decreased roughness significantly. After careful analysis we found out that polished surfaces showed a higher degree for biofilm formation in comparison to the non-polished ones. We also observed that bacteria showed a higher rate for biofilm formation for the demagnetized samples, whereas 0.5T magnetization showed the least amount of biofilm formation. After 0.5T, there was no significant change in the rate of biofilm formation on the stainless-steel samples. Altogether, stainless steel samples containing 0.5 μm and less grainsize, and magnetized with 0.5 tesla and stronger magnets demonstrated the least degree of biofilm formation. DISCUSSION: In summary, the results demonstrate that controlling the grain size of medical grade stainless steel can control and mitigate bacterial responses on, and thus possibly infections of, orthopedic implants or other implantable devices. The research was funded by Komatsuseiki Kosakusho Co., Ltd (KSJ: Japan) SIGNIFICANCE/CLINICAL RELEVANCE: Orthopedic implants that more than 70% of them are made of metals (i.e., stainless steel, titanium, and cobalt-chromium alloys) are failing through loosening and breakage due to their limited mechanical properties. On the other hand, the risk of infection for these implants and its financial burden on our society is undeniable. We have seen that our uniformly nanograined stainless steel shows improved mechanical properties (i.e., higher stiffness, hardness, fatigue) as compared to conventional stainless steel along with the reduction of biofilm formation on its surface. These promising results made us to peruse the development of nanograined titanium and cobalt-chromium alloys for resolving the complications of orthopedic implants.more » « less
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Statement of Purpose: Orthopedic implants are important therapeutic devices for the management of a wide range of orthopedic conditions. However, bacterial infections of orthopedic implants remain a major problem, and not an uncommon one, leading to an increased rate of osteomyelitis, sepsis, implant failure and dysfunction, etc. Treating these infections is more challenging as the causative organism protects itself by the production of a biofilm over the implant’s surface (1). Infections start by the adhesion and colonization of pathogenic bacteria such as Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), Escherichia coli (E. coli), Methicillin-Resistant Staphylococcus aureus (MRSA), and Multi-Drug Resistant Escherichia coli (MDR E. coli) on the implant’s surfaces. Specifically, Staphylococcus comprises up to two-thirds of all pathogens involved in orthopedic implant infections (2). However, bacterial surface adhesion is a complex process influenced by several factors such as chemical composition, hydrophobicity, magnetization, surface charge, and surface roughness of the implant (3). Considering the intimate association between bacteria and the implant surface, we measured the effect of stainless-steel surface properties on bacterial surface attachment and subsequent formation of biofilms controlling above mentioned factors. Method: The prominent bacteria responsible for orthopedic implant infections (SA, SE, E. coli, MRSA, and MDR E. coli) were used in this study. We were able to control the grain size of medical grade 304 and 316L stainless steel without altering their chemical composition (grain size range= 20μm-200nm) (4). Grain size control affected the nano-topography of the material surfaces which was measured by an Atomic Force Microscope (AFM). Grain sizes, such as 0.2, 0.5, 1, 2, 3, 9, and 10 μm, were used both polished and non-polished. All the stainless-steel samples were cleaned by treating with acetone and ethanol under sonication. Triplicates of all polished and non-polished samples with different grain sizes were subjected to magnetization of DM, 0.1T, 0.5T, and 1T, before seeding them with the bacteria. Controls were used in the form of untreated samples. Bacterial were grown in Tryptic Soy Broth (TSB). An actively growing bacterial suspension was seeded onto the stainless-steel discs into 24-well micro-titer plates and kept for incubation. After 24 hours of incubation, the stainless-steel discs were washed with Phosphate Buffer Saline (PBS) to remove the plankton bacteria and allow the sessile bacteria in the biofilm to remain. The degree of development of the bacterial biofilms on the stainless-steel discs were measured using spectrophotometric analysis. For this, the bacterial biofilm was removed from the stainless steel by sonication. The formation of biofilms was also determined by performing a biofilm staining method using Safranin. Results: AFM results revealed a slight decrease in roughness by decreasing the grain size of the material. Moreover, the samples were segregated into two categories of polished and non-polished samples, in which polishing decreased roughness significantly. After careful analysis we found out that polished surfaces showed a higher degree for biofilm formation in comparison to the non-polished ones. We also observed that bacteria showed a higher rate for biofilm formation for the demagnetized samples, whereas 0.5T magnetization showed the least amount of biofilm formation. After 0.5T, there was no significant change in the rate of biofilm formation on the stainless-steel samples. Altogether, stainless steel samples containing 0.5 μm and less grainsize, and magnetized with 0.5 tesla and stronger magnets demonstrated the least degree of biofilm formation. Conclusion: In summary, the results demonstrate that controlling the grain size of medical grade stainless steel can control and mitigate bacterial responses on, and thus possibly infections of, orthopedic implants or other implantable devices. The research was funded by Komatsuseiki Kosakusho Co., Ltd (KSJ: Japan)more » « less
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null (Ed.)Abstract Goal: This work introduces an integrated system incorporated seamlessly with a commercial Foley urinary catheter for bacterial growth sensing and biofilm treatment. Methods: The system is comprised of flexible, interdigitated electrodes incorporated with a urinary catheter via a 3D-printed insert for impedance sensing and bioelectric effect-based treatment. Each of the functions were wirelessly controlled using a custom application that provides a user-friendly interface for communicating with a custom PCB via Bluetooth to facilitate implementation in practice. Results: The integrated catheter system maintains the primary functions of indwelling catheters - urine drainage, balloon inflation - while being capable of detecting the growth of Escherichia coli, with an average decrease in impedance of 13.0% after 24 hours, tested in a newly-developed simulated bladder environment. Furthermore, the system enables bioelectric effect-based biofilm reduction, which is performed by applying a low-intensity electric field that increases the susceptibility of biofilm bacteria to antimicrobials, ultimately reducing the required antibiotic dosage. Conclusion: Overall, this modified catheter system represents a significant step forward for catheter-associated urinary tract infection (CAUTI) management using device-based approaches, integrating flexible electrodes with an actual Foley catheter along with the control electronics and mobile application. Significance: CAUTIs, exacerbated by the emergence of antibiotic-resistant pathogens, represent a significant challenge as one of the most prevalent healthcare-acquired infections. These infections are driven by the colonization of indwelling catheters by bacterial biofilms.more » « less
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/pharmaceutics14081613
