The only types of polyhydroxyalkanoates (PHAs) that have been explored for use in nerve regeneration are poly(3‐hydroxybutyrate), P(3HB), and poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (P(3HB‐co‐3HHx)). However, nerve regeneration induced by these PHAs is inferior to that of autologous nerve grafting. The aim of this work was to study novel PHA blends as resorbable biomaterials for the manufacture of nerve guidance conduits. PHA blend films with varying ratios of poly(3‐hydroxyoctanoate)/poly(3‐hydroxybutyrate) (P(3HO)/P(3HB)) were produced using the solvent‐casting method. Neat films of P(3HO) and P(3HB), along with 25:75, 50:50, and 75:25 blend films of P(3HO)/P(3HB), were characterized with respect to chemical, material, and biological properties. On surface analysis, the blends exhibited higher values of roughness compared with the neat films. The differential scanning calorimetry characterization of the blends confirmed that P(3HO) and P(3HB) formed immiscible blends. FTIR and XRD analysis of the blends showed a decrease in crystallinity along with an increase of the proportion of P(3HO) . However, an increase in the stiffness of the blends was observed when the proportion of P(3HB) increased. Although all of the blends were biocompatible with NG108‐15 neuronal cells, the 25:75 P(3HO)/P(3HB) blend showed significantly better support for growth and differentiation of these cells. The mechanical properties of PHA blends correspond to the reported properties of peripheral nerves. Therefore, they could serve as base material for the manufacture of nerve guidance conduits.

Polyhydroxyalkanoates (PHAs) are a family of prokaryotic‐derived biodegradable and biocompatible natural polymers known to exhibit neuroregenerative properties. In this work, poly(3‐hydroxybutyrate), P(3HB), and poly(3‐hydroxyoctanoate), P(3HO), have been combined to form blend fibres for directional guidance of neuronal cell growth and differentiation. A 25:75 P(3HO)/P(3HB) blend (PHA blend) was used for the manufacturing of electrospun fibres as resorbable scaffolds to be used as internal guidance lumen structures in nerve conduits. The biocompatibility of these fibres was studied using neuronal and Schwann cells. Highly aligned and uniform fibres with varying diameters were fabricated by controlling electrospinning parameters. The resulting fibre diameters were 2.4 ± 0.3, 3.7 ± 0.3, and 13.5 ± 2.3 μm for small, medium, and large diameter fibres, respectively. The cell response to these electrospun fibres was investigated with respect to growth and differentiation. Cell migration observed on the electrospun fibres showed topographical guidance in accordance with the direction of the fibres. The correlation between fibre diameter and neuronal growth under two conditions, individually and in coculture with Schwann cells, was evaluated. Results obtained from both assays revealed that all PHA blend fibre groups were able to support growth and guide aligned distribution of neuronal cells, and there was a direct correlation between the fibre diameter and neuronal growth and differentiation. This work has led to the development of a family of unique biodegradable and highly biocompatible 3D substrates capable of guiding and facilitating the growth, proliferation, and differentiation of neuronal cells as internal structures within nerve conduits.

Essential oils have been used as remedies since ancient times for the treatment of numerous illnesses on account of their wide range of biological activities. Recent preclinical and clinical studies have shown varying pharmacological responses in the nervous system leading to anxiolytic, antidepressant, sedative, and anticonvulsant effects. Experimentation in animal models has evidenced the involvement of multiple neurotransmitter systems in the mode of action of essential oils, resulting in measurable physiological effects in the brain. Additionally, clinical trials have demonstrated the influence of essential oils in physiological parameters such as blood pressure, heart rate, respiratory rate, brain waves composition, and cortisol serum levels with concomitant psychological effects. Although there is growing evidence of measurable effects of essential oils in animal brains, more clinical research is required to validate their influence in the human central nervous system. This will enable the development of essential oil‐based drugs for the treatment of mental illnesses such as depression, anxiety and dementia.

Neurons and glial cells of the central nervous system (CNS) release extracellular vesicles (EVs) to the interstitial fluid of the brain and spinal cord parenchyma. EVs contain proteins, nucleic acids and lipids that can be taken up by, and modulate the behaviour of, neighbouring recipient cells. The functions of EVs have been extensively studied in the context of neurodegenerative diseases. However, mechanisms involved in EV-mediated neuron-glial communication under physiological conditions or healthy ageing remain unclear. A better understanding of the myriad roles of EVs in CNS homeostasis is essential for the development of novel therapeutics to alleviate and reverse neurological disturbances of ageing. Proteomic studies are beginning to reveal cell type-specific EV cargo signatures that may one day allow us to target specific neuronal or glial cell populations in the treatment of debilitating neurological disorders. This review aims to synthesise the current literature regarding EV-mediated cell-cell communication in the brain, predominantly under physiological conditions.