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

Abstract

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.

Transglutaminase-Catalyzed Bottom-Up Synthesis of Polymer Hydrogel

“…Under physiological conditions, thrombin activates the transglutaminase Factor XIII (FXIIIa) and can further stabilizes the clot by cross-linking of fibrin polymers ( Pieters and Wolberg, 2019 ). Therefore, fibrin hydrogels can be formed via the combination of fibrinogen and thrombin mixtures ( Nelson and Gilbert, 2021 ). Abrego et al (2022) compared the elastic properties of fibrin hydrogels and polyethylene glycol (PEG) hydrogels, and found an increase in the elasticity of the hydrogel with higher concentrations of fibrin and PEG, respectively.…”

Sprayable hydrogel for biomedical applications

“…102,104 Moreover, the structure of the fibrin-based hydrogel can be straightforwardly regulated by changing the concentration of thrombin and fibrinogen in the hydrogel precursors. Based on these characteristics, fibrin-based hydrogels are widely applied in bone tissue engineering, 102 neural tissue injury, 105 wound healing, 106 superficial cancer therapies 24,107,108 and so on.…”

Role of Molecular Interactions in Supramolecular Polypeptide–Polyphenol Networks for Engineering Functional Materials

“…This progress has led to the rapid development of nanomaterials for various biomedical applications including disease diagnosis, drug/gene delivery, and tissue engineering. − Synthetic polypeptides (PPeps) and poly­(amino acids), which are composed of amino acids, have emerged as a platform for engineering nanomaterials owing to their facile synthesis, tunable composition, and well-defined sequence and corresponding physicochemical properties . Moreover, PPeps mimic endogenous macromolecules and thereby exhibit excellent biocompatibility and biodegradability as well as tunable biofunctionality. − For instance, polyarginine (PArg) is commonly used as a cell-penetrating peptide for intracellular delivery , and elastin-like PPep-based hydrogels are often used to mimic the extracellular matrix in synthetic biomaterials . In this context, PPep-based materials are generally constructed using different covalent-linking molecules to bridge the PPeps, thereby producing robust functional assemblies. , However, such strategies require complex synthetic steps and toxic cross-linking agents and yield irreversible bonds, which collectively limit the broad use of PPeps as a platform for engineering biomedical materials and advanced therapeutics.…”

“…8−10 For instance, polyarginine (PArg) is commonly used as a cellpenetrating peptide for intracellular delivery 11,12 and elastinlike PPep-based hydrogels are often used to mimic the extracellular matrix in synthetic biomaterials. 13 In this context, PPep-based materials are generally constructed using different covalent-linking molecules to bridge the PPeps, thereby producing robust functional assemblies. 2,14 However, such strategies require complex synthetic steps and toxic crosslinking agents and yield irreversible bonds, which collectively limit the broad use of PPeps as a platform for engineering biomedical materials and advanced therapeutics.…”