Neurological diseases are characterized by the gradual loss of specific brain structures and functions, resulting in cognitive and physical impairment.1 The complexity of the central nervous system (CNS) and limitations in its capacity for spontaneous regeneration represent significant challenges in the search for effective therapies for neurological disorders and related injuries. This sophistication is given by the presence of glial cells that can slow down the capacity for regeneration and increase the complexity of the inflammatory response after an injury, and can also play a beneficial role by providing support and protection to nerve cells during the repair process.2 In this context, hydrogels emerge as promising biomaterials, capable of forming three-dimensional structures that replicate the environment of the extracellular matrix. Hyaluronic acid (HA), a major component of the extracellular matrix in the CNS, is crucial for cellular communication and behavior.3 This study focuses on the development and analysis of a HA hydrogel designed to mimic the properties of extracellular matrix of the CNS. The goal is to create an environment that supports the regeneration and repair of neural tissues, taking advantage of the biomimetic characteristics of the hydrogel to facilitate processes such as cellular communication and neural cell growth. In this study, we employed chemical modification of hyaluronic acid for the formation of a cross-linked HAMA hydrogel using UV light, which mimics the physicochemical properties of the CNS. To determine the degree of functionalization of hyaluronic acid, a proton nuclear magnetic resonance (1H-NMR) analysis was carried out. Brain extracellular matrix (ECM) is embedded in its three-dimensional network to induce a greater cellular response. The characterization of the hydrogel revealed desirable physical properties, such as excellent water absorption capacity and a low modulus. Furthermore, the ability of the ECM to reduce the modulus of the different mixtures was observed. 

In addition, to test its applicability, cylindrical samples of the hydrogel were printed using LCD 3D printers, which maintained their shape and stability for more than a month.

1. Carroll WM. The global burden of neurological disorders. Lancet Neurol. 2019;18(5):418-419. doi:10.1016/S1474-4422(19)30029-8

2. Neuroregeneration—Center for Regenerative Medicine—Mayo Clinic Research. Available online: https://www.mayo.edu/research/centers-programs/center-regenerative-biotherapeutics/focus-areas/neuroregeneration

3. Casini P, Nardi I, Ori M. RHAMM mRNA expression in proliferating and migrating cells of the developing central nervous system. Gene Expr Patterns. 2010;10(2-3):93-97. doi:10.1016/j.gep.2009.12.003