Advanced Materials to Enhance Central Nervous System Tissue Modeling and Cell Therapy

Abstract

The progressively deeper understanding of mechanisms underlying stem cell fate decisions has enabled parallel advances in basic biology-such as the generation of organoid models that can further one's basic understanding of human development and disease-and in clinical translation-including stem cell based therapies to treat human disease. Both of these applications rely on tight control of the stem cell microenvironment to properly modulate cell fate, and materials that can be engineered to interface with cells in a controlled and tunable manner have therefore emerged as valuable tools for guiding stem cell growth and differentiation. With a focus on the central nervous system (CNS), a broad range of material solutions that have been engineered to overcome various hurdles in constructing advanced organoid models and developing effective stem cell therapeutics is reviewed. Finally, regulatory aspects of combined material-cell approaches for CNS therapies are considered.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

“…30 However, the ECM of the central nervous system (CNS) is not solely secreted by astrocytes; other cells, such as neurons, also secrete critical ECM materials. 6 Sood et al demonstrated that porcine decellularized brain ECM hydrogel (DBECMH) promoted more robust neural network formation and axonal lengthening compared to neurons cultured with collagen. 31 Saheli et al reported that organoids cultured in sheep liver ECM hydrogel exhibited stronger hepatocyte function than those in a collagen I-based medium.…”

Cell Development Enhanced Bionic Silk Hydrogel on Remodeling Immune Pathogenesis of Spinal Cord Injury via M2 Polarization of Microglial

“…[ 19 ] Biomaterial scaffolds with tunable mechanical properties and bionic structures have been reported to facilitate cell adhesion/differentiation and neurite regrowth for accelerating nerve repair. [ 20–24 ] Particularly, softer biomaterials encourage neuronal differentiation of NPCs and enable axon regrowth, whereas stiffer biomaterials encourage NPCs to differentiate into astrocytes. [ 25 ] Meanwhile, scaffolds modified with extracellular matrix (ECM)‐mimicking molecules, such as RGD (Arg‐Gly‐Asp) peptides, can provide enhanced cell adhesion cues to facilitate cell attachment and axonal regrowth, and promote anti‐inflammatory M2 macrophage polarization by activating 𝛼 v 𝛽 3 integrin.…”

Biocompatible and Biodegradable Neuromorphic Device Based on Hyaluronic Acid for Implantable Bioelectronics

“…The biocompatibility and biodegradability of neuromorphic devices for implantable bioelectronics must be resolved before implementing in living bodies. [ 8–13 ]…”

“…To overcome such limitations, recent studies have aimed to correct false neural signals using bioelectronics. [5][6][7][8][9] Many researchers have attempted to treat neurodegenerative diseases by inserting neuromorphic devices, which are next-generation electronic devices that mimic the functions and information processing of the biological nervous system, into the body and connecting them to nerves.…”

“…The biocompatibility and biodegradability of neuromorphic devices for implantable bioelectronics must be resolved before implementing in living bodies. [8][9][10][11][12][13] Herein, we propose using a biopolymer, hyaluronic acid (HA), which is a biosynthetic natural material that is present in the skin and has features of biocompatibility and biodegradability, as the switching layer of a neuromorphic device. We fabricated all of the components that made up the neuromorphic device from biocompatible and biodegradable materials that met the requirements of implantable bioelectronics and then evaluated their electrical and synaptic behaviors.…”