12:30pm Wednesday 23 October 2019

IBEC reveals new strategy for regenerating the central nervous system

The results of their research have been published in the latest issue of the journal Biomaterials.

Despite recent advances in understanding the mechanisms of nerve injury, tissue-engineering solutions for repairing damage in the central nervous system (CNS) remain elusive, owing to the crucial and complex role played by the neural stem cell (NSC) niche. This zone, in which stem cells are retained after embryonic development for the production of new cells, exerts a tight control over many crucial tasks such as growth promotion and the recreation of essential biochemical and physical cues for neural cell differentiation.

According to the first author of the paper, Zaida Álvarez of the Biomaterials for Regenerative Therapies group, “in order to develop tissue-engineering strategies to repair damage to the CNS, it is essential to design biomaterials that closely mimic the NSC niche and its physical and biochemical characteristics.”

Enabling the CNS to regenerate could open doors to promising new strategies to tackle accidental damage and degenerative disorders such as Parkinson’s and Alzheimer’s diseases.

In the study headed by Soledad Alcántara of the UB, the team tested types of polylactic acid (PLA) with different proportions of isomers L and D/L, a biodegradable material allowing neural cell adhesion and growth, as materials for nerve regeneration. They found that one type, PLA with a proportion of isomers of 70/30, maintained the important pools of neuronal and glial progenitor cells in vitro. PLA 70/30 was more amorphous, degraded faster and, crucially, released significant amounts of L-lactate, which is essential for the maintenance and differentiation of neural progenitor cells. “The aim of the research was to find a biomaterial able to sustain the population of neural stem cells and to generate new differentiated cells in order to start the development of an implant that allows brain regeneration,” explains Alcántara.

“The mechanical and surface properties of PLA70/30, which we used here in the form of microthin films, make it a good substrate for neural cell adhesion, proliferation and differentiation,” adds. “The physical properties of this material and the release of L-lactate when it degrades, which provides an alternative oxidative substrate for neural cells, act synergistically to modulate progenitor phenotypes.”

The results suggest that the introduction of 3D patterns mimicking the architecture of the embryonic NSC niches on PLA70/30-based scaffolds may be a good starting point for the design of brain-implantable devices. “These will be able to induce or activate existing neural progenitor cells to self-renew and produce new neurons, boosting the CNS regenerative response in situ,” adds the researcher.

The research has been published in the journal Biomaterials in the article “The effect of the composition of PLA films and lactate release on glial and neuronal maturation and the maintenance of the neuronal progenitor niche” by researchers Zaida Álvarez, Miguel A. Mateos-Timoneda, Petra Hyroššová, Oscar Castaño, Josep A. Planell, José C. Perales, Elisabeth Engel and Soledad Alcántara.

The following bodies have participated in the research: the Biomaterials for Regenerative Therapies group of the IBEC, a research centre founded by the Catalan government, the Universitat Politècnica de Catalunya · BarcelonaTech (UPC) and the UB; the Department of Materials Science and Metallurgy of the UPC; the departments of Pathology and Experimental Therapy and Physiological Sciences of the UB; and the Biomedical Research Network Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) of the Carlos III Health Institute.

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