3D presentation of a neurotrophic factor for the regulation of neural progenitor cells. (August 2014)

• Record Type: Journal Article
• Authors: Zhou, Kun; Thouas, George; Bernard, Claude; Forsythe, John S
• Is Part Of: Nanomedicine. Volume 9:Number 8(2014)
• Page Start: 1239
• Page End: 1251
• Publication Date: 2014-08
• Subjects: brain-derived neurotrophic factor -- immobilization -- layer-by-layer -- neural tissue engineering -- polyelectolyte -- self-assembly nanofiber; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.13.112
• Languages: English
• ISSNs: 1743-5889

Abstract

Background: Adequate cell–scaffold interactions and neurotrophin support are essential factors for neural regeneration.Aim: To provide insight into the biofunctionalization of complex 3D scaffolds with nanoscale precision, as well as the effect of spatial distribution of brain-derived neurotrophic factor (BDNF) and its prolonged stimulation in combination with enhanced cell affinity of nanofibrous scaffolds on the survival/proliferation and neurite outgrowth.Methods & materials: We developed a versatile approach using layer-by-layer self-assembly to incorporate cell adhesion and spatial representation of neurotrophic factors into complex nanofibrous scaffolds.Results: Heparin/poly-L -lysine (PLL) polyelectrolyte multilayers (PEMs) were deposited on electrospun poly-ε-caprolatone nanofibers. Well-controlled amounts of BDNF were immobilized on the PEM-modified nanofibers. In addition, longer neurite outgrowth was observed in neural progenitor cells cultured on PLL-terminating PEM scaffolds. The immobilized BDNF on PLL-terminated PEM scaffolds resulted in significantly longer neurites and higher cell numbers (p < 0.01) compared with BDNF-free and BDNF-adsorbed PLL-terminating scaffolds. Interestingly, there was no upregulation of TrkB-FL, TrkB-T1 or GAP-43 mRNAs with immobilized BDNF in day 5 cultures. Discussion &conclusion: This work reinforces the importance of the combinatorial effects of biomaterial scaffold nanostructure and spatial presentation of neurotrophins in directing neural progenitor cell fates. Original submitted 18 January 2013; Revised submitted 3 May 2013