Preparation of drug-loaded pSiNP/PLGA nanofiber scaffolds. (A) Schematic depicting chemistries used to load each drug: “Amine Adsorption Loading” (top) involves pSiNPs whose inner pore walls have been grafted to a primary amine that binds the small molecule drug bpV(HOpic) via electrostatic interactions; “Calcium Silicate Trapping” (middle) involves condensation of the highly negatively charged TrkB aptamer in a calcium silicate matrix contained within the pSiNPs; and “Oxidation Loading” (bottom) involves mild oxidation of the silicon skeleton on the pSiNPs that physically traps the NGF protein within the nanostructure. The relevant particle type is then loaded into a chloroform solution of PLGA and the nanofiber scaffolds are generated by spray nebulization through an airbrush. (B-E) SEM images of (B) PLGA nanofiber controls, (C) bpV(HOpic)-pSiNP/PLGA nanofiber hybrids, (D) TrkB aptamer-pSiNP/PLGA nanofiber hybrids, and (E) NGF-pSiNP/PLGA nanofiber hybrids. (F-I) TEM images of (F) PLGA nanofiber controls, (G) bpV(HOpic)-pSiNP/PLGA nanofiber hybrids, (H) TrkB aptamer-pSiNP/PLGA nanofiber hybrids, and (I) NGF-pSiNP/PLGA nanofiber hybrids. (J) Degree of alignment of nanofibers calculated by measuring the angle of individual fibers relative to the median angle of alignment. All fiber types show similar, uniaxial alignment (n=3). (K) Diameter of nanofibers calculated by measuring the diameter of 30 fibers in each image. Similar diameter ranges are seen between all groups (n=3).