Self-Assembling Hydrogel Structures for Neural Tissue Repair

Abstract

Hydrogel materials have been employed as biological scaffolds for tissue regeneration across a wide range of applications. Their versatility and biomimetic properties make them an optimal choice for treating the complex and delicate milieu of neural tissue damage. Aside from finely tailored hydrogel properties, which aim to mimic healthy physiological tissue, a minimally invasive delivery method is essential to prevent off-target and surgery-related complications. The specific class of injectable hydrogels termed self-assembling peptides (SAPs), provide an ideal combination of in situ polymerization combined with versatility for biofunctionlization, tunable physicochemical properties, and high cytocompatibility. This review identifies design criteria for neural scaffolds based upon key cellular interactions with the neural extracellular matrix (ECM), with emphasis on aspects that are reproducible in a biomaterial environment. Examples of the most recent SAPs and modification methods are presented, with a focus on biological, mechanical, and topographical cues. Furthermore, SAP electrical properties and methods to provide appropriate electrical and electrochemical cues are widely discussed, in light of the endogenous electrical activity of neural tissue as well as the clinical effectiveness of stimulation treatments. Recent applications of SAP materials in neural repair and electrical stimulation therapies are highlighted, identifying research gaps in the field of hydrogels for neural regeneration.

Boosted Cross-Linking and Characterization of High-Performing Self-Assembling Peptides

“…SAP scaffolds are mimicry of the extracellular matrix (ECM), provide biochemical cues triggering biological response (e.g., cell adhesion, proliferation and differentiation), and thanks to their intrinsic versatility, they can be used for studying Alzheimer's disease [7], the regeneration of spinal cord and brain injuries [8,9], in cartilage tissue engineering [10], in cell and organoid culturing [11], drug discovery [12], bioimaging and drug delivery [13]. Nonetheless, SAPs usually give yield to soft fragile hydrogels, suited for soft tissue regeneration or as fillers [14] (Figure 1): that is why recent efforts have been focused on enhancing the mechanical properties of SAP hydrogels to match those of the tissues to be regenerated [15][16][17][18][19]. While multi-functionalization (i.e., biomimetic property) and their modifications can be considered as accomplished milestones for LDLK-or RADA-based SAPs [21]], tuning their stiffness across various orders of magnitude, in order to match that one of various living tissues (Figure 1) [20], is still an open quest.…”

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

“…Conversely, biomaterials fabricated for internal injection have relatively high viscosity and soft mechanical strength with more cohesive and gel-like characteristics. Currently, a number of studies have investigated the effects of structural (mechanical) and chemical characteristics of biomaterials on various cellular functions such as self-renewability, migratory capacity, and metabolic activity ( Ma et al, 2019 ; Zhao X. et al, 2021 ; Peressotti et al, 2021 ).…”

“…Thus, decellularized ovarian ECM-based scaffold provides an optimal and native 3D microenvironment to enhance the therapeutic effects of administered stem cells. Indeed, Pennarossa et al (2021) produced a decellularized ovarian bioscaffold, which mimics the microarchitecture and biological signals in natural ovarian tissue, and the differentiated mature ovarian cells derived from female germline stem cells were repopulated on decellularized bioscaffolds. Similarly, Hassanpour et al (2018) developed a human decellularized ovarian scaffold seeded with Wharton jelly-derived MSCs.…”

Editorial: Special Issue on Advanced Biomedical Hydrogels

“…Hydrogels can also provide biological, electrical, chemical, and topological cues to guide cells to tissue repair and regeneration. For example, Green and co-workers review the field of self-assembling peptide-containing hydrogels that have been developed to guide neural repair through biomimetic cues, including electrical properties . Heilshorn and colleagues developed elastin-like protein hydrogels for use as an intraluminal filler for improvement of peripheral nerve regeneration in silicone conduits .…”