PMID- 29600349 OWN - NLM STAT- MEDLINE DCOM- 20190118 LR - 20210109 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 55 IP - 12 DP - 2018 Dec TI - Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric Scaffolds for Neural Tissue Engineering and Neuronal Regeneration. PG - 8788-8798 LID - 10.1007/s12035-018-1022-z [doi] AB - 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-epsilon-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. FAU - Limongi, T AU - Limongi T AD - 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. FAU - Rocchi, A AU - Rocchi A AD - Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy. FAU - Cesca, F AU - Cesca F AD - Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy. FAU - Tan, H AU - Tan H AD - Analytical Core Lab, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia. FAU - Miele, E AU - Miele E AD - Nanostructures Department, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy. AD - Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore. FAU - Giugni, A AU - Giugni A AD - 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. FAU - Orlando, M AU - Orlando M AD - Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy. AD - Department of Neurophysiology, NeuroCure Excellence Cluster, Charite Universitats Medizin, Chariteplatz 1, 10117, Berlin, Germany. FAU - Perrone Donnorso, M AU - Perrone Donnorso M AD - Nanostructures Department, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy. FAU - Perozziello, G AU - Perozziello G AD - Laboratory of Nanotechnology BioNEM Department of Experimental and Clinical Medicine, University "Magna Graecia" of Catanzaro, Viale Europa, Catanzaro, Italy. FAU - Benfenati, Fabio AU - Benfenati F AUID- ORCID: 0000-0002-0653-8368 AD - Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genoa, Italy. fabio.benfenati@iit.it. FAU - Di Fabrizio, Enzo AU - Di Fabrizio E AD - 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. enzo.difabrizio@kaust.edu.sa. LA - eng GR - 604263/Neuroscaffolds/ GR - 2014-2015/Compagnia di San Paolo/ PT - Journal Article DEP - 20180329 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Biocompatible Materials) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Polyesters) RN - 0 (Polymers) RN - 24980-41-4 (polycaprolactone) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Astrocytes/cytology/ultrastructure MH - Biocompatible Materials/*chemistry MH - Biomarkers/metabolism MH - Brain-Derived Neurotrophic Factor/*administration & dosage MH - Cell Adhesion MH - Cell Survival MH - Cells, Cultured MH - *Drug Delivery Systems MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Mice, Inbred C57BL MH - *Nerve Regeneration MH - Nerve Tissue/*physiology MH - Neurons/cytology/ultrastructure MH - Polyesters/chemistry MH - Polymers/*chemistry MH - Signal Transduction MH - Synapses/metabolism MH - Tissue Engineering/*methods MH - Tissue Scaffolds/*chemistry OTO - NOTNLM OT - BDNF OT - Biopolymer OT - Drug delivery OT - Microfabrication OT - Neural tissue engineering OT - Primary neurons EDAT- 2018/03/31 06:00 MHDA- 2019/01/19 06:00 CRDT- 2018/03/31 06:00 PHST- 2017/09/14 00:00 [received] PHST- 2018/03/16 00:00 [accepted] PHST- 2018/03/31 06:00 [pubmed] PHST- 2019/01/19 06:00 [medline] PHST- 2018/03/31 06:00 [entrez] AID - 10.1007/s12035-018-1022-z [pii] AID - 10.1007/s12035-018-1022-z [doi] PST - ppublish SO - Mol Neurobiol. 2018 Dec;55(12):8788-8798. doi: 10.1007/s12035-018-1022-z. Epub 2018 Mar 29.