Researchers have taken an important step toward creating ideal repair material by combining water–filled particles known as microgels with robust polymer networks made of natural fibrin. In a remarkable dynamic process, the microgels self–assemble into three–dimensional tunnel–like structures that could allow repair cells to migrate through the polymer network to begin the healing process.

The research was reported in the journal Proceedings of the National Academy of Sciences journal.

“This is a novel demonstration of a biological use for super soft particle systems, which are widely studied in the physics community. They could allow cells to migrate through what is actually a relatively hard material whose strength is provided by the bulk fibrin,” said Thomas Barker, a professor in the Department of Biomedical Engineering at the University of Virginia and the paper’s corresponding author.

In the fibrin matrix created by the research team, the colloidal hydrogels move slowly, passing by each other as water molecules pass each other as they flow into a sink. But the hydrogel particles move much more slowly than water molecules, taking perhaps an hour to pass by another particle, explained Alberto Fernandez–Nieves, an associate professor in the School of Physics at the Georgia Institute of Technology and one the paper’s senior authors.

“The softness of the microgel particles allows them to pass by each other, and that is a key ingredient in allowing cells to move into the material,” Fernandez–Nieves explained.

In real injuries, blood coagulation forms a fibrin mesh from the polymerization of fibrinogen, a natural protein. The mesh stops the bleeding, but repair cells must break down the fibrin network before they can begin the repair and regeneration process. Letting cells migrate through the fibrin–microgel material could accelerate the healing process.

The researchers were surprised to see that cells known as fibroblasts could migrate through the composite material they made.

“In this new material, cell motility is not restricted in what is otherwise a very tightly packed area,” Barker said. “Conventional wisdom and decades of data would tell us that the cells would not move in these colloidal domains, yet we see the cells moving faster than if there were nothing there. The colloidal domains that form in fibrin comprised of these unique ‘squishy’ particles display physical properties that are very different from what people would expect, and are very attractive for biomedical applications.”

Because of the unusual way in which microgel particles are crosslinked, the poly(N–isopropylacrylamide) particles are very soft – softer than living cells.

Former Georgia Tech graduate student Alison Douglas created the fibrin–microgel composites in the laboratory, varying the composition and examining the resulting network under a microscope. As the fibrin polymerized, the particles formed pockets that continued to rearrange themselves even after the fibrin network was fully formed. The pockets created tunnels that led through the fibrin network. With help from graduate student Alexandros Fragkopoulos, they used home–built Matlab codes to characterize the structure and architecture of the resulting material.

Living fibroblast cells were applied to the structure, and the researchers found that the cells were able to penetrate into the fibrin–microgel network. The cells were unable to enter a control network made without the microgels.

“The speed of the cells is related to the time required for the microgels to rearrange themselves,” Fernandez–Nieves said. “You get a fibrin network with microgel pockets that percolate through it. There are tunnel–like pockets in the network that are filled with microgels, and the cells are able to exploit the long–time flow beh