Hydrogels and cryogels as in vitro engineered 3D neurodegenerative models: scope and significance

Neurodegenerative diseases (NDs) represent a diverse set of incurable and debilitating conditions that have become increasingly prevalent in recent years. A thorough understanding of the causes and mechanisms underlying these diseases is needed in order to develop effective treatments. Model systems-in vitro as well as in vivo have helped the researchers gain insights into the disease mechanisms. However, these model systems are unable to precisely mimic the pathophysiology of NDs, making them less physiologically relevant. Therefore, to bridge this gap, 3D in vitro model systems are being developed, which are better suited to recapitulate the specific features of NDs. Unlike other reviews that address these 3D in vitro model systems in a broader sense, without considering the unique material characteristics and applications of specific scaffold types, this review focuses exclusively on biomaterial-based 3D in vitro model systems, viz. hydrogels and their technically evolved versions-cryogels. Both these classes of biomaterials possess tunable physical and chemical properties, thereby serving as advanced models for NDs. This comprehensive review provides a detailed insight into hydrogel- and cryogel-based 3D culture systems, comparing their structural characteristics, mechanical design and bio-functionality, along with their ability to mimic the complex pathological processes occurring in neurodegeneration. By critically assessing their advantages and limitations, we bring to notice their overall physiological relevance as far as understanding NDs is concerned. These 3D models upon subsequent improvisation and validation could potentially be used in various aspects of drug discovery and development, starting from drug screening to early target identification for the development of neurotherapeutics.