Porous Silicon Nanoparticles Embedded in Poly(lactic‐co‐glycolic acid) Nanofiber Scaffolds Deliver Neurotrophic Payloads to Enhance Neuronal Growth

Abstract

Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are pre-loaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle-drug-polymer hybrids are prepared in the form of oriented poly(lactic-co-glycolic acid) nanofiber scaffolds. We test three different therapeutic payloads: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin-related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water-soluble payloads. The drug-loaded pSiNP-nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug-free control nanofibers in a dorsal root ganglion explant assay.

Recent advances in hybrid system of porous silicon nanoparticles and biocompatible polymers for biomedical applications

“…For a clear comparison of three polymers, time-gated imaging was The range of neurite extensions and the average length of the ten longest neurites on the hybrid nanofibers. The Copyright (2020) Wiley-VCH [32] measured, and pSiNPs/PLGA hybrid nanofibers(16-fold than PLA, 120-fold than PCL) displayed the highest signal increase. This study suggests that DNA-based molecules can also be utilized using hybrid nanofiber systems fabricated using a straightforward and cost-effective airbrush.…”

“…However, the synthesis process is tricky because the percentage of polymer penetrating the pores should be regulated. The pSiNPs-embedded polymer (C) is also one of the hybrid formulations that are embedded with different nano sizes of particles in the polymer matrix by encapsulating the entire porous silicon nanoparticles with a polymer [30][31][32][33]. The polymer-coated pSi (D) formulation has a similar design to the polymer-infiltrated pSi method [34][35][36][37].…”

“…Three different types of therapeutic substances were loaded into hybrid nanofibers such as (i) bpV(HOpic): a drug which inhibits phosphatase (loading method: electrostatic adsorption), (ii) tensin homolog (PTEN, TrkB aptamer): an RNA aptamer for tropomyosin-related kinase receptor type B (loading method: calcium silicate condensation), (iii) protein (NGF): a nerve growth factor (loading method: oxidative trapping) (Fig. 4a; [top] The inner pore walls of pSi were modified to a positive charge by amine functionalization for the loading bpV(Hopic), which is a negative charge drug, using electrostatic interactions, [middle] Negatively charged TrkB aptamer was loaded by calcium trapping method, [bottom] NGF protein was loaded into oxidized pores by physical trapping) [32]. The average diameter and charge of the final individual hybrid nanofiber were identified using dynamic light scattering (DLS), zeta potential (PLGA only: 209 ± 60 nm, bpV(HOpic) loaded nanofiber: 211 ± 78 nm, TrkB loaded nanofiber: 213 ± 60 nm, NGF loaded nanofiber: 250 ± 79 nm).…”

Spray‐n‐Sense: Sprayable Nanofibers for On‐Site Chemical Sensing

“…for reliable point-of-analysis detection of analytes in real settings. [38][39][40][41] Previously, nanofibers based sensors have been demonstrated for colorimetric sensing, but the nanofibers are prepared using electrospinning. [8,42,43] However, with the electrospinning process the nanofibers can only be sprayed onto conducting surfaces and requires ultra-high voltage (>10 000 V), which is not suitable for in-field application.…”

Brain-Targeted Dual Site-Selective Functionalized Poly(β-Amino Esters) Delivery Platform for Nerve Regeneration

“…43 Dorsal root ganglion (DRG) neurons, separated from the dorsal column of a rat spinal cord, could regenerate from their central explants to peripheral nerves after stimulation with NGF, BDNF, and other neurotrophins. 44 Therefore, the length of neurite outgrowth was generally used to evaluate bioactive compounds for axon growth promotion. 45 To further verify whether the NGF peptide could promote neurite outgrowth, DRG explants were coincubated with NGF and PAE/NGF and then stained by neurofilaments (Figures 3E and S19).…”