Medical implants can save lives or dramatically improve quality of life, but to our immune system they can appear like intruders.
Rice University bioengineer Omid Veiseh and collaborators have found that the deposition of lipids on implant surfaces can mediate between the body and the implants, with some lipids acting as peacekeepers while others stir up conflict.
“We learned that when immune cells crawl over an implanted biomaterial, they leave behind lipid vesicles that signal to the host immune system whether the biomaterials should be ignored or isolated from the body,” said Veiseh, assistant professor of rice in bioengineering and cancer prevention. and researcher at the Texas Research Institute.
This knowledge might help scientists develop biomaterials or coatings for implants that deflect aggression from the host immune system, thereby reducing malfunction rates of biomedical devices such as pacemakers, cerebrospinal fluid shunts , coronary stents, surgical nets, drug delivery pumps, biosensors, etc.
The study is published in Advanced materials.
“A major problem in all biomedical implants is that the immune system attacks them,” said Christian Schreib, a graduate student at Rice and lead author of the study. “Essentially, it encapsulates them in a fibrous capsule that destroys their functionality and prevents them from working.”
“Our team was able to develop a chemical surface modification that preferentially recruits macrophages that leave behind a lipid-vesicular ‘do not attack’ signature allowing the implants to exist in the body without being recognized as foreign,” Veiseh said.
Fibrosis, or scarring, is the buildup of excess tissue at the site of an injury. The fibrotic response to implants has traditionally been associated with protein deposition on the implanted surface.
“In our research, we realized that while protein is important, fat molecules also play an important role in the fibrotic process,” Schreib said. “We identified two lipid profiles, fatty acids and phospholipids. Fatty acids are more likely to elicit an immune response, while phospholipids are more likely to go unnoticed and not irritate the immune system.
“Now that we understand this, we can use this knowledge to design materials for use in implants that are less likely to trigger an immune response. We might, for example, design a material that attracts phospholipids, so that when you implant the material, the phospholipids naturally deposit on it and help it evade the immune system. We might also consider taking these fat molecules like phospholipids and chemically functionalizing them on the surface of the device prior to implantation.
When an immune response is triggered in the body, immune cells are mobilized to the site of injury or intrusion. The increased traffic of immune cells close to the implant leads to greater accumulation of fibrous tissue.
“A thick layer of cells deposited on the implant is likely to prevent it from working,” Schreib said. “But if you have an atomic-scale lipid layer, it won’t affect its functionality to the same extent.”
Optimizing the performance of implants is critical for patient groups that depend on them for the management of chronic and life-threatening conditions such as hydrocephalus, a disorder that involves excessive buildup of cerebrospinal fluid (CSF) in the brain . For many patients, the only effective management strategy is placement of a CSF shunt that diverts excess fluid to another body cavity. Pediatric patients with hydrocephalus face particularly high rates of implant failure, which can lead to headaches, vomiting, vision loss, brain damage, and death if not treated promptly. .
“As a pediatric neurosurgeon, it’s safe to say that shunt dysfunction is the bane of my existence,” said Dr. Brian Hanak, assistant professor of neurosurgery at University of Toronto Children’s Hospital. Loma Linda in California, co-author of the study. While CSF shunt dysfunction can occur in any age group, dysfunction rates are much higher in young children. “Most of us working in this field think it’s probably related to the fact that the brain’s innate immune system is particularly activated in young children,” he said.
“In young children and babies, rates of shunt dysfunction are in the range of 40% to 50% two years following implantation. Frankly, I’m embarrassed to routinely implant the most failure-prone life support device in modern medicine. If you developed a pacemaker with a 40% to 50% failure rate at two years, it would never get US Food and Drug Administration approval, because it’s terrible. But this is unfortunately the industry standard for CSF shunts.
Hanak said many brain implants might benefit from a reduced innate immune response.
“One in particular that always comes to mind is brain-computer interface technology,” he said. “It’s been regarding 20 years now since we had proof of concept that you can implant an array of microelectrodes in someone’s brain and have them use that array to control a robotic arm.
“You might ask, if so, why isn’t this technology something every paralyzed person can use to improve their independence and quality of life? The reason for this is that the immune response mounted on these implanted electrode arrays renders them unable to register neuronal activity beyond two to three years in vivo. At the moment, with our current state of technology, it’s not really a viable solution, certainly not a long-term solution for paralyzed patients.
Les National Institutes of Health (R01 DK120459), la Defense Advanced Research Projects Agency (D20AC00002), la Rice University Academy Fellowship, la Shared Equipment Authority de Rice et la National Science Foundation (CBET1626418) ont soutenu la recherche.