The third place entry came from Kaitlyn Sadtler from Johns Hopkins University, with her submission entitled: “Engineering Pro-Regenerative Immunotherapies.”
When thinking about the cutting edge of biomedical treatment, regeneration of lost limbs strikes many people with rapt fascination. Watching a salamander regrow its leg begs the question; could humans ever do the same? Post doctoral fellow, Kaitlyn Sadtler at Johns Hopkins University, who studies this problem, discovered an unexpected healing ability of the immune system.
Although the immune system is celebrated as a guardian against pathogens, it plays an important role in regeneration. Immune cells, early responders to any wound site, scavenge dead cells, direct the growth of other cells that eventually replace missing tissue, and encourage the development of new blood vessels to supply nutrients.
The immune system comprises many different cell types but macrophages—large white blood cells that engulf foreign particles—are especially important for regeneration. Salamanders lacking macrophages form permanent scar tissue instead of regenerating amputated legs. Scientists also observed that mouse embryos, which can repair wounds without scarring like the salamander, have a high population of macrophages that are particularly concentrated in developing limbs. By prompting human macrophages to act like those found in salamanders or mouse embryos, researchers are hoping to unlock new regenerative abilities in humans.
Kaitlyn Sadtler has discovered a new way to activate macrophages by manipulating collagen, a protein found in connective tissue that is also the main ingredient in animal based glues and gelatin. Sadtler’s breakthrough uses structures called “collagen scaffolds” which are engineered by first purifying collagen from bone and tendon into a powdered form and then molding the collagen into small discs or cubes. These scaffolds can then be placed directly into wounds or what Sadtler terms, “tissue gaps.”
To test if collagen scaffolds could aid healing, Sadtler implanted them into mice with traumatic leg wounds. After six weeks, injured mice were able to run as far on a treadmill as normal mice. More importantly, Sadtler’s detailed analysis revealed how collagen scaffolds sparked communication between immune cells to orchestrate the macrophages’ healing ability. In particular, a previously underappreciated cell called “type 2 helper T cells,” were instrumental in activating macrophages. These T cells, most well known for triggering allergies, had never been associated with regeneration before.
Sadtler’s thesis advisor and collaborator, Drew Pardoll M.D. Ph.D. and director of the Bloomberg-Kimml Institute for Cancer Immunotherapy, predicted that her study would serve as an “inflection point where regenerative immunology goes from an idea into a field of serious study.”
Sadtler’s efforts also foreshadows a growing movement towards collaboration between immunologists and engineers. “The integration of the two fields is relatively new in the context of modern immunotherapies and immune response to scaffolds,” Sadtler says. “Both fields carry their own language and set of baseline principles or skills. Additionally, engineers and immunologists can approach a problem in very different manners. As these scientists are brought together through collaborative projects, the engineers benefit from the vast knowledge of the intricate workings of the immune system by immunologists, and immunologists benefit from the tools and materials that are synthesized with precision by engineers.”
In the future, Sadtler imagines immunologists and engineers creating a “tunable regenerative scaffold that could combine different elements to elicit certain immune responses.” By modifying the structure or chemical composition of the scaffolds, researchers could stimulate a specific pattern of immune response to deal with a range of traumas ranging from burns, to severe lacerations, or infection.