Authors:

Daniela Ramirez Castellanos

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About Paper:

The brain extracellular matrix is mainly composed of proteins and polysaccharides such as hyaluronan (HA), which plays a key role in tissue hydration, mechanical support, and signaling processes. The unique composition of brain tissue significantly affects drug transport and thus limits therapeutic delivery . Additionally, many drug candidates fail during clinical trials, which highlights the importance of creating more physiologically relevant in vitro models that improve preclinical testing of intrathecally injected therapeutics for neurological disorders. In this context, the present work aims to synthesize and characterize HA hydrogels as tissue mimics of the brain, with the ultimate goal of testing drug transport across brain-like matrices. HA was first thiolated to varying degrees, and the hydrogels were synthesized via polyethylene glycol diacrylate, divinyl sulfone, and ferric sodium EDTA crosslinking methods, targeting a physiological pH of 7.4 for the three formulations. The hydrogels were characterized based on pH, gelation, HA retention, macromolecular transport, microscopic structure, cell encapsulation, and rheological behavior. The expected outcomes of the project include obtaining uniform and soft hydrogels with appropriate stability and a tortuous structure that mimics the brain tissue and its main transport phenomena properties. As a conclusion, the present study offers a new approach to tissue mimic fabrication by focusing on HA as one of the main brain ECM components. Future directions include refining the synthesis method to develop a gel formulation that more closely replicates the native composition of brain tissue. Keywords: Hyaluronan; Brain; Tissue Mimics; Hydrogel; Characterization

Source:

Purdue University / 2025

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Co-authors:

Daniela Ramirez Castellanos