title: Mesoporous silica nanoparticle-based substrates for cell directed delivery of Notch signalling modulators to control myoblast differentiation.
abstract: Biochemical cues are critical to control stem cell function and can be utilized to develop smart biomaterials for stem cell engineering. The challenge is to deliver these cues in a restricted manner with spatial and temporal control. Here we have developed bilayer films of mesoporous silica nanoparticles for delayed cellular delivery of Notch modulators to promote muscle stem cell differentiation. We demonstrate that drug-loaded particles are internalized from the particle-covered surface, which allows for direct delivery of the drug into the cell and a delayed and confined drug release. Substrates of particles loaded with γ-secretase-inhibitors, which block the Notch signalling pathway, promoted efficient differentiation of myoblasts. The particle substrates were fully biocompatible and did not interfere with the inherent differentiation process. We further demonstrate that impregnating commercially available, biocompatible polymer scaffolds with MSNs allows for a free standing substrate for cell directed drug delivery.
authors: Institute of Inorganic Chemistry II, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany. mlinden@uni-ulm.de.
authors: Dominique
authors: D
authors: Böcking
authors: Oliver
authors: O
authors: Wiltschka
authors: Jenni
authors: J
authors: Niinimäki
authors: Hussein
authors: H
authors: Shokry
authors: Rolf
authors: R
authors: Brenner
authors: Mika
authors: M
authors: Lindén
authors: Cecilia
authors: C
authors: Sahlgren
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects*; D004337:Drug Carriers; D051379:Mice; D008855:Microscopy, Electron, Scanning; D032446:Myoblasts / Q000166:cytology*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D051880:Receptors, Notch / Q000737:chemistry*; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000737:chemistry*; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D051880:Receptors, Notch; D012822:Silicon Dioxide; D053829:Amyloid Precursor Protein Secretases