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

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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.

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Funding

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).

Author information

Author notes

  1. E. Miele

    Present address: Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore

  2. M. Orlando

    Present address: Department of Neurophysiology, NeuroCure Excellence Cluster, Charité Universitäts Medizin, Charitéplatz 1, 10117, Berlin, Germany

  3. T. Limongi and A. Rocchi contributed equally to this work.

Authors and Affiliations

  1. SMILEs Lab, Physical Science and Engineering (PSE) and Biological and Environmental Science and Engineering (BESE) Divisions, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia

    T. Limongi, A. Giugni & Enzo Di Fabrizio

  2. Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy

    A. Rocchi, F. Cesca, M. Orlando & Fabio Benfenati

  3. Analytical Core Lab, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia

    H. Tan

  4. Nanostructures Department, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy

    E. Miele & M. Perrone Donnorso

  5. Laboratory of Nanotechnology BioNEM Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, Viale Europa, Catanzaro, Italy

    G. Perozziello

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  1. T. Limongi
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  11. Enzo Di Fabrizio
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Corresponding authors

Correspondence to Fabio Benfenati or Enzo Di Fabrizio.

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The authors declare that they have no competing interest.

Additional information

F. Benfenati and E. Di Fabrizio are senior authors and corresponders.

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Limongi, T., Rocchi, A., Cesca, F. et al. Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric Scaffolds for Neural Tissue Engineering and Neuronal Regeneration. Mol Neurobiol 55, 8788–8798 (2018). https://doi.org/10.1007/s12035-018-1022-z

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