(420a) Infection-Resisting Biomaterials
AIChE Annual Meeting
Plenary Session: Multifunctional Biomaterials Addressing Current Healthcare Challenges (Invited Talks)
Tuesday, October 30, 2018 - 5:10pm to 5:35pm
The synthetic surfaces associated with tissue-contacting biomedical devices are attractive to many bacteria, because these surfaces provide anchoring sites, often well protected from the innate immune response, in a moist environment with abundant access to nutrients. Clinically, bacterial colonization of device surfaces is significant, because a series of revision surgeries is often required to resolve the resulting implant-associated infection. The impact on both the patient and the health-care system can be substantial. While better surgical practice can mitigate the chances of infection, eliminating bacterial surface colonization is in large measure an engineering problem. One solution has been to incorporate antimicrobials into the device. These then elute into the surrounding physiological system over extended time periods after surgery. This approach, while FDA-approved in a small number of applications such as antibiotic-loaded bone cement, delivers antibiotic whether it is needed or not, and it thus runs counter to the rapidly increasing concerns about the overuse of antibiotics and the ongoing evolution of antibiotic-resistant bacterial strains. An alternate concept is that of self-defensive surfaces. These sequester antimicrobials until their release in response to a bacterial trigger. Sequestered antimicrobials are present only in very small amounts, and they are released only if needed. Consequently, they do not contribute to the development of resistance. This presentation describes work using anionic microgels to create self-defensive surfaces. These charged microgels can be electrostatically deposited onto surfaces and subsequently loaded with small-molecule cationic antimicrobials by complexation processes. We have identified conditions where complexed antimicrobials remain sequestered for several weeks despite the fact that a diffusion-based elution process would take only seconds. These sequestered antimicrobials can, however, be released when closely approached by bacteria. Contact creates a steep chemical-potential gradient that drives antimicrobial transfer from the microgels to the bacterial envelope where there is a high concentration of negative charge. This transfer kills the bacteria. Metabolizing tissue cells in contact with the same microgel-modified surfaces are, however, unable to trigger antimicrobial release, indicating that the contact-transfer mechanism is specific to bacteria. Such specificity is critical for designing future biomaterials that not only promote healing but simultaneously resist infection.