Bacteria-Triggered Antimicrobial Release from Microgel-Modified Surfaces

Project: Research project

Project Details

Description

Technical Abstract: This project combines emerging concepts of bacteria-triggered release, contact bacterial killing, and differential cell interactions to construct a new means with which to render tissue-contacting biomaterial surfaces resistant to bacterial colonization. The primary scientific objective is to understand the materials properties governing the triggered release of complexation-sequestered cationic antimicrobials. This project will: (1) identify a set of antimicrobial peptides (AMPs) with varying charge, charge distribution, and hydrophobicity that can complex within model, surface-immobilized, anionic micro hydrogels (microgels) under four-week exposure to physiological buffer conditions; (2) show that sequestered peptides are protected from proteolytic degradation; (3) establish whether AMP release from the microgels can be triggered by direct physico-chemical contact with bacteria; (4) determine whether direct physicochemical contact with tissue cells (e.g. macrophages) triggers AMP release; and (5) demonstrate that AMP-loaded microgel-modified surfaces resist bacterial colonization while still enabling the integration of tissue cells. The intellectual merit of this research work centers on the fact that this project will provide insights into the relative roles of electrostatic and hydrophobic interactions between small-molecule cationic antimicrobials and synthetic anionic microgels. This basic information will guide the future design of new microgels with enhanced charge, charge distribution, and hydrophobicity that can broaden the bacteria-triggered release mechanisms to an even wider range of antimicrobials. Significantly, this project will also involve both graduate and undergraduate research students who will work not only at Stevens but also in close collaboration with colleagues from Zimmer Trabecular Metals and will benefit from both the basic academic and applied industrial perspectives of this project.

Non-Technical Abstract: Most of us know someone who has had a hip or knee replacement. Such joint replacement has become common and can have a very positive impact on the quality of life. Many people are unaware, however, that joint replacements can fail, most commonly because of infection. Failure due to infection also occurs in other implants like hernia meshes, pacemakers, and heart valves. Infection occurs when bacteria adhere to the implant surface and grow into colonies called biofilms, like the stuff that grows on our teeth when we don?t brush. Importantly, antibiotics don't kill bacteria in a biofilm. So, we have to develop implant surfaces that inhibit bacteria fro' adhering. Then, for those bacteria that do manage to adhere, we need to kill them before they form a biofilm. This isn't an easy problem. The problem is further complicated by the fact that the FDA is understandably reluctant to approve implantable biomedical devices that incorporate antibiotics into them, because, in the many cases where infection is not a problem, the unneeded antibiotics help cultivate resistant bacteria like MRSA. This research project, funded by the Biomaterials Program within the National Science Foundation's Division of Materials Research, is designed to understand the fundamental science that can enable a new technology to prevent implant infection. The idea is to cover an implant surface with microscope particles called microgels and load them with bacteria-killing molecules called antimicrobial peptides. The central scientific problem is to understand how to keep these antimicrobial peptides trapped inside the microgels unless a bacterium happens to come along. At that point, and only at that point, the microgels have to be designed to release the peptide and kill the bacterium. If NSF-funded scientists can figure out how to accomplish this task, people needing biomedical implants will have a greater probability of surgical success with healthier outcomes.

StatusFinished
Effective start/end date1/07/1631/12/21

Funding

  • National Science Foundation

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