by Keyword: Lactate

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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

Regenerative medicine strategies to promote recovery following traumatic brain injuries are currently focused on the use of biomaterials as delivery systems for cells or bioactive molecules. This study shows that cell-free biomimetic scaffolds consisting of radially aligned electrospun poly-l/dl lactic acid (PLA70/30) nanofibers release l-lactate and reproduce the 3D organization and supportive function of radial glia embryonic neural stem cells. The topology of PLA nanofibers supports neuronal migration while l-lactate released during PLA degradation acts as an alternative fuel for neurons and is required for progenitor maintenance. Radial scaffolds implanted into cavities made in the postnatal mouse brain fostered complete implant vascularization, sustained neurogenesis, and allowed the long-term survival and integration of the newly generated neurons. Our results suggest that the endogenous central nervous system is capable of regeneration through the invivo dedifferentiation induced by biophysical and metabolic cues, with no need for exogenous cells, growth factors, or genetic manipulation.

Keywords: Lactate, Nanofibers, Neural stem cells, Neurogenesis, Regeneration, Vascularization

Álvarez, Zaida, Mateos-Timoneda, Miguel A., Hyrossová, Petra, Castaño, Oscar, Planell, Josep A., Perales, José C., Engel, Elisabeth, Alcántara, Soledad, (2013). The effect of the composition of PLA films and lactate release on glial and neuronal maturation and the maintenance of the neuronal progenitor niche Biomaterials , 34, (9), 2221-2233

To develop tissue engineering strategies useful for repairing damage in the central nervous system (CNS) it is essential to design scaffolds that emulate the NSC niche and its tight control of neural cell genesis, growth, and differentiation. In this study we tested two types of poly l/dl lactic acid (PLA95/5 and PLA70/30), a biodegradable material permissive for neural cell adhesion and growth, as materials for nerve regeneration. Both PLA were slightly hydrophobic and negatively charged but differed in crystallinity, stiffness and degradation rate. PLA95/5 films were highly crystalline, stiff (GPa), and did not degrade significantly in the one-month period analyzed in culture. In contrast, PLA70/30 films were more amorphous, softer (MPa) and degraded faster, releasing significant amounts of lactate into the culture medium. PLA70/30 performs better than PLA95/5 for primary cortical neural cell adhesion, proliferation and differentiation, maintaining the pools of neuronal and glial progenitor cells in vitro. l-lactate in the medium recapitulated PLA70/30's maintenance of neuronal restricted progenitors but did not sustain bipotential or glial restricted progenitors in the cultures, as occurred when neural cells were grown on PLA70/30. Our results suggest that PLA70/30 may mimic some of the physical and biochemical characteristics of the NSC niche. Its mechanical and surface properties may act synergistically in the modulation of bipotential and glial restricted progenitor phenotypes, while it is l-lactate, either added to the medium or released by the film that drives the maintenance of neuronal restricted progenitor cell phenotypes.

Keywords: Polylactic acid, Degradation, Neurons, Progenitors, Lactate, Glial cells, NSC niche