PMID- 25787735 OWN - NLM STAT- MEDLINE DCOM- 20160104 LR - 20181113 IS - 2190-3948 (Electronic) IS - 2190-393X (Linking) VI - 5 IP - 2 DP - 2015 Apr TI - Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells. PG - 89-100 LID - 10.1007/s13346-013-0131-5 [doi] AB - The treatment of an injured central nervous system using stem-cell-based regenerative medicine still faces considerable hurdles that need to be overcome. Chief among which is the lack of efficient strategies to generate functional neurons from stem cells. The sustained delivery of biochemical cues and synergistic topographical signaling from electrospun nanofibrous scaffolds may be a potential strategy to enhance neuronal differentiation of stem cells for therapeutic purposes. In this study, retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) were encapsulated into a copolymer of epsilon-caprolactone and ethyl ethylene phosphate to form a multifunctional, electrospun nanofibrous scaffold. Sustained release of RA and BDNF was achieved for at least 7 and 14 days, respectively. Despite lower cumulative release of drugs as compared to bolus delivery to plain nanofibers (at least 2x and 50x lower for RA and BDNF, respectively), nanofiber-mediated delivery of RA and/or BDNF resulted in similar capacity for neuronal differentiation of mouse neural progenitor cells (NPCs). In addition, nanofiber topography significantly increased neuronal differentiation (with BDNF, 47.4% Map2(+) cells on 2D vs. 53.4 to 56.5% on nanofibers, p < 0.05) and reduced glial cell differentiation. BDNF was a more potent inducer of neuronal differentiation than RA. RA supplementation alone resulted in minimal effect on NPC differentiation, and dual supplementation of RA and BDNF did not further enhance the neuronal differentiation of NPCs. Collectively, the results suggest that synergistic effects of nanofiber topography and sustained delivery of RA and/or BDNF may contribute towards the design of a multifunctional artificial stem cell niche for NPC neuronal differentiation. FAU - Low, Wei Ching AU - Low WC AD - Division of Chemical and Biomolecular Engineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Nanyang, 637459, Singapore. FAU - Rujitanaroj, Pim-On AU - Rujitanaroj PO FAU - Wang, Feng AU - Wang F FAU - Wang, Jun AU - Wang J FAU - Chew, Sing Yian AU - Chew SY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Drug Deliv Transl Res JT - Drug delivery and translational research JID - 101540061 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Caproates) RN - 0 (Lactones) RN - 5688UTC01R (Tretinoin) RN - 56RE988L1R (caprolactone) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*administration & dosage MH - Caproates/chemistry MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Lactones/chemistry MH - Mice, Inbred C57BL MH - Microscopy, Electron, Scanning MH - Nanofibers/*administration & dosage/ultrastructure MH - Neural Stem Cells/cytology/*drug effects MH - Neurons/cytology MH - Tretinoin/*administration & dosage EDAT- 2015/03/20 06:00 MHDA- 2016/01/05 06:00 CRDT- 2015/03/20 06:00 PHST- 2015/03/20 06:00 [entrez] PHST- 2015/03/20 06:00 [pubmed] PHST- 2016/01/05 06:00 [medline] AID - 10.1007/s13346-013-0131-5 [doi] PST - ppublish SO - Drug Deliv Transl Res. 2015 Apr;5(2):89-100. doi: 10.1007/s13346-013-0131-5.