Biodegradable Microcapsules Loaded with Nerve Growth Factor Enable Neurite Guidance and Synapse Formation

Abstract

Neurological disorders and traumas often involve loss of specific neuronal connections, which would require intervention with high spatial precision. We have previously demonstrated the biocompatibility and therapeutic potential of the layer-by-layer (LbL)-fabricated microcapsules aimed at the localized delivery of specific channel blockers to peripheral nerves. Here, we explore the potential of LbL-microcapsules to enable site-specific, directional action of neurotrophins to stimulate neuronal morphogenesis and synaptic circuit formation. We find that nanoengineered biodegradable microcapsules loaded with nerve growth factor (NGF) can guide the morphological development of hippocampal neurons in vitro. The presence of NGF-loaded microcapsules or their clusters increases the neurite outgrowth rate while boosting neurite branching. Microcapsule clusters appear to guide the trajectory of developing individual axons leading to the formation of functional synapses. Our observations highlight the potential of NGF-loaded, biodegradable LbL-microcapsules to help guide axonal development and possibly circuit regeneration in neuropathology.

Perillaldehyde improves cognitive function in vivo and in vitro by inhibiting neuronal damage via blocking TRPM2/NMDAR pathway

“…mNGF is implicated in nourishing, preserving and promoting the survival and growth of synapses [ 28 ]. Some studies showed that the pathogenesis of Alzheimer’s disease (AD) and vascular dementia (VD) was related to the lack of mNGF protection [ 29 ].…”

Connecting the Neurobiology of Developmental Brain Injury: Neuronal Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target

“…A multidisciplinary approach has led to the development of a biodegradable microcapsule containing NGF that can be delivered to the targeted cells. They successfully showed that NGF-loaded microcapsules increase neurite outgrowth, branching complexity, and synapse formation in primary rat hippocampal and astrocyte co-cultures [ 181 ]. This work has the potential to enable neurite morphological and functional reconstruction and possible circuit regeneration by delivering capsules directly into the affected area.…”

Unveiling the Assembly of Neutral Marine Polysaccharides into Electrostatic-Driven Layer-by-Layer Bioassemblies by Chemical Functionalization

“…However, since the LbL assembly process can occur under mild conditions in entirely aqueous solutions, the electrostatic interaction has been extended well beyond the assembly of oppositely charged polyelectrolytes. In fact, an unlimited number of charged materials, including biomolecules such as marine polysaccharides [ 17 , 18 , 19 , 20 ], proteins [ 21 ], enzymes [ 22 , 23 ], nucleic acids [ 24 ], or growth factors [ 25 ], which have limited solubility in nonaqueous solutions and may lose their biological activity, have been processed into electrostatic-driven functional multilayered assemblies for addressing a wide variety of biomedical and biotechnological applications. In particular, marine polysaccharides, which are widely discarded as waste in the processing of marine organisms, are particularly attractive ingredients for enabling the assembly of sustainable biomaterials in an LbL fashion owing to their very appealing features [ 26 ].…”