Helping the brain rebuild itself

In the study, headed by Dr. Soledad Alcántara from the Neural Development Group at the University of Barcelona, the scientists found that implants made of biodegradable polylactic acid (PLA) nanofibers reproduce some aspects of the natural embryonic brain environment and encourage tissue to regrow.

Image: Scaffolds of random (left) and aligned (right) nanofibers after 1 week of implantation in mouse cerebral cortex. Glial cells (green) and blood vessels (red) only penetrate in the aligned scaffold, and not in the random fibers (dashes).

These implants, known in tissue engineering as scaffolds, release L-lactate, a common cellular cue that induces angiogenesis; and they also mimic the neurogenic niche – the environment in which the brain develops – allowing neural progenitors to generate new neurons and glial cells that migrate in the same way as during brain development.

“Brain injuries are common causes of disability, with loss of nerve tissue due to secondary degeneration, and often the formation of cavities that inhibit neural cell growth,” says Zaida Álvarez of IBEC’s Biomaterials for Regenerative Therapies group and Neural Development group at UB, first author on the paper. “To find effective regenerative strategies to promote brain recovery after traumatic injury, we need to focus on solving the current obstacles: poor implant integration, vascularization and cell survival.”

When the PLA scaffolds designed at IBEC were implanted in newborn mice, L-lactate released during degradation acted as an alternative ‘fuel’ for growing neurons and activated endogenous progenitors. Secondly, the fibers used to build the ‘frame’ reproduced the natural 3D organization and topology of the embryonic radial glia, which supports neuronal migration and vascularization during brain growth.

“By means of our tuned biomaterials, it may be possible to regulate the biophysical and metabolic parameters leading to the restoration of functional central nervous system tissue lost after traumatic brain injury without the need for exogenous cells, growth factors, or genetic manipulation,” says Zaida. “Although there is a long way to go before these experiments can be translated to the clinic – and we still need to see if a similarly regenerative response occurs in adults – our results open up unexpected and exciting perspectives in the design of cell-free implantable devices.”

Reference article: Álvarez, Z., Castaño, O., Castells, A.A., Mateos-Timoneda, M.A., Planell, J.A., Engel, E. & Alcántara, S. (2014). Neurogenesis and vascularization of the damaged brain using a lactate-releasing biomimetic scaffold. Biomaterials, 35, 17, 4769–4781

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