Creating a slippery slope on the surface of medical implants
(Boston)–Implanted medical devices such as left ventricular-assist devices for patients with heart failure or other support systems for patients with respiratory, liver or other end organ disease save lives every day. However, bacteria that form infectious biofilms on those devices, called device-associated infections, not only often sabotage their success but also contribute to the rampant increase in antibiotic resistance currently seen in hospitals.
As reported in Biomaterials, a team led by Joanna Aizenberg, Ph.D., and Elliot Chaikof, M.D., Ph.D., at the Wyss Institute for Biologically Inspired Engineering and the Harvard John A. Paulson School of Engineering and Applied Sciences at Harvard University (SEAS), as well as the Beth Israel Deaconess Medical Center (BIDMC), has created self-healing slippery surface coatings with medical-grade teflon materials and liquids that prevent biofilm formation on medical implants while preserving normal innate immune responses against pathogenic bacteria.
The technology is based on the concept of 'slippery liquid-infused porous surfaces' (SLIPS) developed by Aizenberg, who is a Wyss Institute Core Faculty member, Professor of Chemistry and Chemical Biology and the Amy Smith Berylson Professor of Materials Science at SEAS. Inspired by the carnivorous Nepenthes pitcher plant, which uses the porous surface of its leaves to immobilize a layer of liquid water, creating a slippery surface for capturing insects, Aizenberg previously engineered industrial and medical surface coatings that are able to repel unwanted substances as diverse as ice, crude oil and biological materials.
"We are developing SLIPS recipes for a variety of medical applications by working with different medical-grade materials, tuning the chemical and physical features of these solids and the infused lubricants to ensure the stability of the coating, and carefully pairing the non-fouling properties of the integrated SLIPS materials to specific disturbing factors, contaminating environments and performance requirements," said Aizenberg. "Here we have extended our repertoire of materials classes and applied the SLIPS concept very convincingly to medical-grade teflon, demonstrating its enormous potential in implanted devices prone to bacterial fouling and infection."
First, the team searched ex vivo for the teflon material that would work best with a selection of compatible lubricants to provide a long-lived repellent surface against a common device-associated bacterial strain. The most advantageous teflon-lubricant combinations had to preserve the anti-bacterial activity of innate immune cells that provide the natural first-line response against invading bacteria. The winning material was 'expanded polytetrafluoroethylene' (ePTFE). Used in prosthetic grafts for cardiovascular reconstruction, mesh for hernia repair, as well as implants in a wide variety of reconstructive surgery, ePTFE tested well with lubricants with proven acceptable safety profiles.
Moving to a rodent model, the team compared bacterial and tissue responses to implanted hernia meshes with or without a SLIPS surface after infecting the animals with Staphylococcus aureus.
"SLIPS coatings yielded extremely favorable responses in vivo: they resisted infection by bacteria and were associated with considerably less infiltrating immune cells and inflammatory abscesses than non-coated ePTFE," said Chaikof, who is a Wyss Institute Associate Faculty member, Chairman of the Roberta and Stephen R. Weiner Department of Surgery and Surgeon-in-Chief at BIDMC.
"At present, patients who receive implants for the repair, reconstruction or replacement of diseased or damaged organs or tissues or otherwise depend upon temporary life sustaining support systems, often require antibiotics at the time of implantation to keep the risk of bacterial infection at bay. SLIPS coatings one day could obviate the widespread use of antibiotics, minimize the development of antibiotic resistant microorganisms, and enhance the capacity of temporary or permanent artificial devices to resist infection," said Chaikof.
"This new study by Joanna and Elliot exemplifies the Wyss Institute model in which collaborations between basic scientists focused on industrial applications and clinicians working in the medical area are fostered in a way that can lead to unexpected developments — in this case, one that has the potential to have a major positive impact in the clinical setting," said Don Ingber, M.D., Ph.D., Founding Director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at SEAS.
Previous medical SLIPS applications include coatings that can repel bacteria and blood from small medical implants, tools and surgical instruments that are made of steel or, more recently, coatings that help keep the glass surfaces of endoscopy and bronchoscopy lenses free from highly contaminating body fluids and thus transparent during procedures.
Wyss Institute for Biologically Inspired Engineering at Harvard University
Benjamin Boettner, [email protected], +1 917-913-8051
Wyss Institute for Biologically Inspired Engineering at Harvard University
Seth Kroll, [email protected], +1 617-432-7758
The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new startups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, Charité – Universitätsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology.
The Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and The Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox.
The Harvard John A. Paulson School of Engineering and Applied Sciences serves as the connector and integrator of Harvard's teaching and research efforts in engineering, applied sciences, and technology. Through collaboration with researchers from all parts of Harvard, other universities, and corporate and foundational partners, we bring discovery and innovation directly to bear on improving human life and society.