De novo hyaluronic acid-based biomaterial: a promising perspective to manage neurodegenerative diseases

Hyaluronic acid (HA) is a polysaccharide in the extracellular matrix (ECM) that controls cell function in neural tissue through cellular receptors. These functions include migration, proliferation, immunoregulation, differentiation, and inflammatory processes critical in regulating central nervous system (CNS) homeostasis. However, this balance is often disrupted following damage or illness, leading to remarkable variations in the ECM milieu and cell actions. This balance disturbance can interfere with intrinsic homeostatic mechanisms that protect critical cells and tissues' safety and functionality in the CNS. Researchers have explored HA-based tissue engineering developments for regenerative and medical procedures in the nervous system to minimize brain detriment. Initially, the efficacy of HA in regeneration is linked to its impact on cellular signaling pathways and its potency to modify biological and mechanical characteristics. This overview focuses on recent studies that examine the use of HA-based biomaterials for drug delivery, scaffolds, microparticles, nanocomposites, modification strategies of HA, and its incorporation into different nanomaterials and nanocarriers (NCs) in the treatment of various CNS diseases. Overall, using natural polymers in nanotechnology for drug delivery has the potential to slow down the progression of neurological diseases (ND) and improve therapeutic outcomes.