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Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric Scaffolds for Neural Tissue Engineering and Neuronal Regeneration

  • T. Limongi
  • A. Rocchi
  • F. Cesca
  • H. Tan
  • E. Miele
  • A. Giugni
  • M. Orlando
  • M. Perrone Donnorso
  • G. Perozziello
  • Fabio Benfenati
  • Enzo Di Fabrizio
Article

Abstract

Biopolymers are increasingly employed for neuroscience applications as scaffolds to drive and promote neural regrowth, thanks to their ability to mediate the upload and subsequent release of active molecules and drugs. Synthetic degradable polymers are characterized by different responses ranging from tunable distension or shrinkage to total dissolution, depending on the function they are designed for. In this paper we present a biocompatible microfabricated poly-ε-caprolactone (PCL) scaffold for primary neuron growth and maturation that has been optimized for the in vitro controlled release of brain-derived neurotrophic factor (BDNF). We demonstrate that the designed morphology confers to these devices an enhanced drug delivery capability with respect to monolithic unstructured supports. After incubation with BDNF, micropillared PCL devices progressively release the neurotrophin over 21 days in vitro. Moreover, the bioactivity of released BDNF is confirmed using primary neuronal cultures, where it mediates a consistent activation of BDNF signaling cascades, increased synaptic density, and neuronal survival. These results provide the proof-of-principle on the fabrication process of micropatterned PCL devices, which represent a promising therapeutic option to enhance neuronal regeneration after lesion and for neural tissue engineering and prosthetics.

Keywords

Microfabrication Biopolymer Drug delivery Primary neurons BDNF Neural tissue engineering 

Notes

Funding Information

The work was supported by the King Abdullah University of Science and Technology start-up funding and by research grants from the European Union FP7 “Neuroscaffolds” (grant number 604263 to FB), Compagnia di San Paolo-Italy (to FC).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interest.

Supplementary material

12035_2018_1022_MOESM1_ESM.docx (153 kb)
ESM 1 (DOCX 153 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.SMILEs Lab, Physical Science and Engineering (PSE) and Biological and Environmental Science and Engineering (BESE) DivisionsKing Abdullah University of Science and TechnologyThuwalKingdom of Saudi Arabia
  2. 2.Center for Synaptic Neuroscience and TechnologyIstituto Italiano di TecnologiaGenoaItaly
  3. 3.Analytical Core LabKing Abdullah University of Science and TechnologyThuwalKingdom of Saudi Arabia
  4. 4.Nanostructures DepartmentIstituto Italiano di TecnologiaGenoaItaly
  5. 5.Centre for BioImaging Sciences, Department of Biological SciencesNational University of SingaporeSingaporeSingapore
  6. 6.Department of Neurophysiology, NeuroCure Excellence ClusterCharité Universitäts MedizinBerlinGermany
  7. 7.Laboratory of Nanotechnology BioNEM Department of Experimental and Clinical MedicineUniversity “Magna Graecia” of CatanzaroCatanzaroItaly

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