Injectable Scaffold Helps the Brain Rebuild After Stroke, Mouse Study Finds

Biomedical engineers at Duke University have created an injectable biomaterial that may help the brain recover from damage left behind by an ischemic stroke, in which a blood clot blocks blood flow to part of the brain. In experiments with mice, the material transformed the cavity created by lost brain tissue into a more favorable environment for healing, recruiting the body's own immune cells, encouraging new blood vessels, supporting changes in neural tissue, and improving motor function. The findings were published in Cell Biomaterials.

Emergency treatments such as clot-dissolving drugs can restore blood flow and save still-viable brain tissue, but once tissue has died, restoring circulation cannot replace what is lost, leaving a cavity that rehabilitation alone cannot rebuild. "Once brain tissue has been lost, restoring blood flow is no longer enough," said Tatiana Segura, a professor of biomedical engineering at Duke. Her team used microporous annealed particle scaffolds, hydrogel microparticles that assemble into a porous structure cells can enter and use while rebuilding neural tissue.

The researchers collected extracellular vesicles, tiny packages of proteins, lipids and genetic material released by astrocytes, star-shaped brain cells that respond to injury, and chemically attached them to the scaffold's surface so their signals stayed concentrated in the damaged area. One signaling combination, of the molecules IL-4 and C1q, was especially effective at drawing in helpful immune cells, including macrophages and a persistent population of neutrophils, cells usually linked to inflammation and damage in early stroke. When the researchers reduced the neutrophil population, blood vessel formation declined substantially, showing these cells were playing an important role in healing.

As immune cells entered the treated area, new blood vessels formed throughout the stroke cavity, and researchers found more axonal fibers, the structures that let brain cells transmit signals, in and around the injured region. Mice treated with the scaffold performed better on a grid-walking test measuring forelimb placement, and by eight weeks their performance could not be statistically distinguished from healthy mice, with the improvement persisting for the rest of the study. The extracellular vesicles alone, without the scaffold, failed to produce comparable blood vessel repair. The approach remains preclinical: researchers have so far tested it only in mouse models, injecting the material directly into the damaged brain area.