Extracellular Matrix‐Mimetic Hydrogels for Treating Neural Tissue Injury: A Focus on Fibrin, Hyaluronic Acid, and Elastin‐Like Polypeptide Hydrogels

Neurological and functional recovery is limited following central nervous system injury and severe injury to the peripheral nervous system. Extracellular matrix (ECM)‐mimetic hydrogels are of particular interest as regenerative scaffolds for the injured nervous system as they provide 3D bioactive interfaces that modulate cellular response to the injury environment and provide naturally degradable scaffolding for effective tissue remodeling. In this review, three unique ECM‐mimetic hydrogels used in models of neural injury are reviewed: fibrin hydrogels, which rely on a naturally occurring enzymatic gelation, hyaluronic acid hydrogels, which require chemical modification prior to chemical crosslinking, and elastin‐like polypeptide (ELP) hydrogels, which exhibit a temperature‐sensitive gelation. The hydrogels are reviewed by summarizing their unique biological properties, their use as drug depots, and their combination with other biomaterials, such as electrospun fibers and nanoparticles. This review is the first to focus on these three ECM‐mimetic hydrogels for their use in neural tissue engineering. Additionally, this is the first review to summarize the use of ELP hydrogels for nervous system applications. ECM‐mimetic hydrogels have shown great promise in preclinical models of neural injury and future advancements in their design and use can likely lead to viable treatments for patients with neural injury. Fibrin, hyaluronic acid (HA), and elastin‐like polypeptide (ELP) hydrogels are mimetic of the extracellular matrix but have different gelation schemes and bioactive properties. Fibrin has found a niche in spinal cord injury models while HA has become popular for ischemia models. ELP hydrogels have rarely been integrated into neural in vivo models but provide a promising substrate for future use.