Orthopedic implants that reconstruct joints or repair trauma are continuously increasing in sophistication and prevalence, restoring function and mobility for over a million patients annually. The global market is expected to reach $30 billion in 2012 and $46.5 billion in 2017. However, about 1% of hip implants, 4% of knee implants, and more than 15% of implants associated with orthopedic trauma fail because of infection. Dr. Matthew Libera of the Department of Chemical Engineering and Materials Science, in collaboration with faculty across numerous disciplines at Stevens Institute of Technology, has been working to radically change implant design to minimize the risk of infection. Dr. Libera has been awarded a patent titled “Surfaces Differentially Adhesive to Bacteria & Eukaryotic Cells” for a technology that repels bacteria and promotes the growth of bone cells around an implant.
In addition to the repellent and adhesive properties of the surface, Dr. Libera’s technology releases antimicrobial compounds to fight bacteria. As opposed to delivering antibiotics systemically by taking them orally, the medicine is localized right at the surfaces of the implant. The surfaces can also release growth factors to promote better cell interactions, thus improving the adhesion of good cells to the implant and enhancing the development of healthy tissue.
“This patent award is the latest in a series of very significant Stevens contributions to the development of new infection-resisting biomaterials,” says Dr. Michael Bruno, Dean of the Charles V. Schaefer, Jr. School of Engineering and Science. Dr. Christos Christodoulatos, Vice Provost for the Office of Innovation and Entrepreneurship, says, “Collaborative efforts here have created a fertile environment for innovation, resulting in robust and multifaceted technologies that can add tremendous value to medical devices.” In addition to work by Libera and his research group, Dr. Svetlana Sukhishvili is applying her internationally recognized expertise on water-soluble polymers and self assembly to develop new infection-resisting coatings; Dr. James Liang is developing new families of highly effective antimicrobial peptides; Dr. Xiaojun Yu has been working with chitosan-based materials with novel anti-infective properties to make nanofiber structures for advanced tissue-engineering applications; and Dr. Woo Lee and Dr. Hongjun Wang are engineering innovative 3-D tissue models to test advanced cell-interactive materials in ways that go well beyond traditional cell-culture methods using petri dishes.
Implants and biomedical devices have gradually become more advanced, using refined designs such as varying roughness to control how bone cells (osteoblasts) grow and attach to an implant. However, the surface structures and chemistries that promote healthy cell growth also tend to encourage the undesirable growth of bacteria, and this leads to infection. Bacterial cells can reach a thick biofilm state in which they are thousands of times more resistant to antibiotics. “Usually the only way to resolve a biomaterials-associated infection is to remove the device, treat the infected tissue, and later implant a second device,” says Dr. Libera. “Not only does this bring really significant cost to the health-care system, it forces the patient to undergo a lengthy and challenging surgical and rehabilitation process over a long period of time. We would like to eliminate that risk.”
Sponsored primarily by the Army Research Office due to the frequency of infection in both injured soldiers and civilians, Dr. Libera has modified surfaces with microgels, which are hydrogels (the same type of material used to make soft contact lenses) that are microscopic in size, typically 200-400 nanometers in diameter. They are affixed to the surface of an implantable device using self assembly. When a device is immersed in a colloidal solution of the microgels, the implant, whose surface has been given a positive electric charge, attracts negatively charged microgels. Because of their negative charge, once on the device surface the microgels repel each other and create an evenly spaced patchwork. This patchwork is highly desirable because the space between microgels is about the size of a bacterial cell (1 micrometer; for reference, a human hair is about 75 micrometers thick), so the surface repels bacteria. Bone tissue cells are larger than bacterial cells and have fluid cell membranes that can conform to the surface. Data shows that bone cells will grow over the microgels and stick to exposed surface between the microgels. "We refer to these surfaces as differentially adhesive," says Libera, "because they allow the good cells to adhere but repel the bacterial cells."
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