Neurogenesis and vascularization of the damaged brain using a lactate-releasing biomimetic scaffold

Zaida Álvarez, Oscar Castaño, Alba A. Castells, Miguel A. Mateos-Timoneda, Josep A. Planell, Elisabeth Engel, Soledad Alcántara*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4769-4781
Number of pages13
JournalBiomaterials
Volume35
Issue number17
DOIs
StatePublished - Jun 2014

Keywords

  • Lactate
  • Nanofibers
  • Neural stem cells
  • Neurogenesis
  • Regeneration
  • Vascularization

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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