Abstract:Despite considerable research and development efforts, the problem of infections related to biomedical devices and implants persists. Bacteria evidently can readily colonize surfaces of synthetic materials, such as those used for the fabrication of catheters, hip and knee implants, and many other devices. As the growing colony encapsulates itself with a protective exocellular bacterial polysaccharide layer, the biofilm becomes much harder to combat than circulating bacteria. Thus, there is a strong need to mit… Show more
“…These sites could conceivably be used to attach a different biomolecule, for example, one with an orthogonal activity. Thus, our preliminary results suggest surprising versatility in this approach: quorum-sensing molecules could be simultaneously or sequentially attached in combination with other biomolecules, such as antimicrobial agents, enzymes, or perhaps quorum-sensing compounds that target other bacteria 39–41 .…”
Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors including virulence factor secretion and biofilm formation. Quorum sensing relies on production, release, accumulation, and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. We investigate key features of the compounds, linkers, and surfaces necessary to appropriately position molecules to interact with cognate receptors, and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components, and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviors of bacteria on surfaces.
“…These sites could conceivably be used to attach a different biomolecule, for example, one with an orthogonal activity. Thus, our preliminary results suggest surprising versatility in this approach: quorum-sensing molecules could be simultaneously or sequentially attached in combination with other biomolecules, such as antimicrobial agents, enzymes, or perhaps quorum-sensing compounds that target other bacteria 39–41 .…”
Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors including virulence factor secretion and biofilm formation. Quorum sensing relies on production, release, accumulation, and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. We investigate key features of the compounds, linkers, and surfaces necessary to appropriately position molecules to interact with cognate receptors, and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components, and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviors of bacteria on surfaces.
“…Dulbecco's modified eagle medium (DMEM), fetal bovine serum (FBS), 0.05% Trypsin EDTA, and phosphate buffer saline (PBS, pH=7. 4) were purchased from Gibco (USA). Methanol and trifluoroethanol (TFE) were purchased from Alfa-Aesar Chemical Inc. (USA).…”
Section: Methodsmentioning
confidence: 99%
“…Infection is currently considered as the major reason for GTR/GBR failure in clinical applications, constituting a significant healthcare burden [4]. Infection is caused by either bacterial colonization at the wound site or foreign body response resulting from the implant material [5].Antibacterial biomaterials are one of the greatest interests in the war against implant-related infections, representing the broadest group of anti-infective biomaterials [6].…”
Email address: sharell@126.com (R. Shi).
AbstractInfection is the major reason for guided tissue regeneration/guided bone regeneration (GTR/GBR) membrane failure in clinical application. In this work, we developed GTR/GBR membranes with localized drug delivery function to prevent infection by electrospinning of poly(ε-caprolactone) (PCL) and gelatin blended with metronidazole (MNA). Acetic acid (HAc) was introduced to improve the miscibility of PCL and gelatin to fabricate homogeneous hybrid nanofiber membranes. The effects of the addition of HAc and the MNA content (0,1,5,10,20,30, and 40 wt.% of polymer) on the properties of the membranes were investigated. The membranes showed good mechanical properties, appropriate biodegradation rate and barrier function. The controlled and sustained release of MNA from the membranes significantly prevented the colonization of anaerobic bacteria. Cells could adhere to and proliferate on the membranes without cytotoxicity until the MNA content reached 30%.Subcutaneous implantation in rabbits for 8 months demonstrated that MNA-loaded membranes evoked a less severe inflammatory response depending on the dose of MNA than bare membranes. The biodegradation time of the membranes was appropriate for tissue regeneration. These results indicated the potential for using MNA-loaded PCL/gelatin electrospun membranes as anti-infective GTR/GBR membranes to optimize clinical application of GTR/GBR strategies.
“…[1,2] This has stimulated a search for polymers and other materials that resist the attachment of pathogens, or that exhibit antibacterial or bacteriostatic properties. [3][4][5][6][7][8][9] Materials discovery is now increasingly been carried out using high throughput synthesis and characterization methods so that novel, useful areas of materials property space can be identified. [10][11][12][13][14][15][16][17][18][19] While high throughput experimental techniques can dramatically accelerate new materials discovery, it is essential that complementary computational and informatics techniques are also are also be used.…”
Infection by pathogenic bacteria on implanted and indwelling medical devices during surgery causes large morbidity and mortality worldwide. Attempts to ameliorate this important medical issue have included development of antimicrobial surfaces on materials, 'no touch' surgical procedures, and development of materials with inherent low pathogen attachment.The search for new materials is increasingly being carried out by high throughput methods.Efficient methods for extracting knowledge from these large data sets are essential. We used data from a large polymer microarray exposed to three clinical pathogens to derive robust and predictive machine-learning models of pathogen attachment. The models could predict pathogen attachment for the polymer library quantitatively. The models also successfully 22222222224222 predicted pathogen attachment for a second-generation library, and identified polymer surface chemistries that enhance or diminish pathogen attachment.
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