Conductive Collagen-Based Hydrogel Combined With Electrical Stimulation to Promote Neural Stem Cell Proliferation and Differentiation

Abstract

Injectable biomimetic hydrogels are a promising strategy for enhancing tissue repair after spinal cord injury (SCI) by restoring electrical signals and increasing stem cell differentiation. However, fabricating hydrogels that simultaneously exhibit high electrical conductivities, excellent mechanical properties, and biocompatibility remains a great challenge. In the present study, a collagen-based self-assembling cross-linking polymer network (SCPN) hydrogel containing poly-pyrrole (PPy), which imparted electroconductive properties, is developed for potential application in SCI repair. The prepared collagen/polypyrrole (Col/PPy)-based hydrogel exhibited a continuous and porous structure with pore sizes ranging from 50 to 200 μm. Mechanical test results indicated that the Young’s moduli of the prepared hydrogels were remarkably enhanced with PPy content in the range 0–40 mM. The conductivity of Col/PPy40 hydrogel was 0.176 ± 0.07 S/cm, which was beneficial for mediating electrical signals between tissues and accelerating the rate of nerve repair. The investigations of swelling and degradation of the hydrogels indicated that PPy chains interpenetrated and entangled with the collagen, thereby tightening the network structure of the hydrogel and improving its stability. The cell count kit-8 (CCK-8) assay and live/dead staining assay demonstrated that Col/PPy40 coupled with electrical simulation promoted the proliferation and survival of neural stem cells (NSCs). Compared with the other groups, the immunocytochemical analysis, qPCR, and Western blot studies suggested that Col/PPy40 coupled with ES maximally induced the differentiation of NSCs into neurons and inhibited the differentiation of NSCs into astrocytes. The results also indicated that the neurons in ES-treated Col/PPy40 hydrogel have longer neurites (170.8 ± 37.2 μm) and greater numbers of branch points (4.7 ± 1.2). Therefore, the prepared hydrogel system coupled with ES has potential prospects in the field of SCI treatment.

Hydrogel and Nanomedicine‐Based Multimodal Therapeutic Strategies for Spinal Cord Injury

“…Davaa et al [57] transplanted NSCs through a collagen hydrogel to the SCI site in SCI model rats, and the results indicated that the collagen hydrogel protected the NSCs from a severe inflammatory environment, allowing the differentiation of NSCs and recovery of the spinal cord (Figure 3a). Xu et al [89] and Yang et al [86] demonstrated that a collagen hydrogel induces in situ NSCs to form neurons and reduces the accumulation of astrocytes, leading to the recovery of damaged spinal cord tissues. In addition, collagen hydrogels are used to deliver drugs to injury sites.…”

“…Xu et al. [ 89 ] and Yang et al [ 86 ] demonstrated that a collagen hydrogel induces in situ NSCs to form neurons and reduces the accumulation of astrocytes, leading to the recovery of damaged spinal cord tissues. In addition, collagen hydrogels are used to deliver drugs to injury sites.…”

Advances in the Translation of Electrochemical Hydrogel‐Based Sensors

“…[ 12 ] While collagen is normally not conductive, the combination with PPy increased the conductivity to 17.6 S m −1 , which demonstrates advantages of hybrid copolymer formulations. [ 124 ] While the porcine tissue model provides a highly complex environment that properly mimics in vivo sensing conditions, many uncontrollable metabolic mechanisms that can be otherwise readily tuned in cell culture are left unmonitored in tissue samples. As such, the presence of aerobic metabolizing microorganisms that consume glucose in the porcine tissue can alter the readouts, which was indeed confirmed by standard glucose assays, resulting in a sensor viability lifetime of under 5 days.…”

Development of Electro‐Conductive Composite Bioinks for Electrohydrodynamic Bioprinting with Microscale Resolution

“…[ 4,5 ] The 3D bioprinted hydrogels with customized structures, intrinsic bioactivity, and biocompatibility provide extracellular matrix (ECM)‐mimetic microenvironments for cell proliferation, migration, and maturation, which have attracted tremendous attention in tissue engineering, disease modeling, drug screening, etc. [ 6–9 ]…”

“…[4,5] The 3D bioprinted hydrogels with customized structures, intrinsic bioactivity, and biocompatibility provide extracellular matrix (ECM)-mimetic microenvironments for cell proliferation, migration, and maturation, which have attracted tremendous attention in tissue engineering, disease modeling, drug screening, etc. [6][7][8][9] Recent studies have further revealed the importance of providing electrical cues to the living cells within 3D bioprinted constructs, which can mediate the growth and differentiation of cells for various electroactive tissue repairing applications, e.g., cardiac, skeletal, smooth muscles, and neural tissues. [10][11][12][13] And, electro-conductive biomaterials have been demonstrated to promote the proliferation and differentiation behavior of electrical stimuli-responsive cells, such as neuron cells, [14] bone cells, [15] and muscle cells.…”