Synergistic effects of conductivity and cell-imprinted topography of chitosan-polyaniline based scaffolds for neural differentiation of adipose-derived stem cells

Abstract

Smart nano-environments that mimic the stem cell niche can guide cell behavior to support functional repair and regeneration of tissues. The specific microenvironment of nervous tissue is composed of several physical signaling factors, including proper topography, flexibility, and electric conductance. In this study, a cell-imprinting technique was used to obtain a hierarchical topographical conductive scaffold based on chitosan-polyaniline (PANI) hydrogels for directing the neural differentiation of rat adipose-derived stem cells (rADSCs). A chitosan-polyaniline hydrogel was synthesized, followed by characterization tests, such as Fourier transform infrared spectroscopy (FTIR), electrical conductivity, Young modulus, and contact angle measurements. A chitosan-PANI scaffold with a biomimetic topography was fabricated by molding it on a chemically fixed culture of PC12 cells. This substrate was used to test the hypothesis that the PC12 cell-imprinted chitosan-PANI hydrogel provides the required hierarchical topographical surface to induce neural differentiation. To test the importance of spatial imprinting, rADSCs were seeded on these conductive patterned substrates, and the resulting cultures were compared to those of the same cells grown on flat conductive chitosan-polyaniline, and flat pure chitosan substrates for evaluation of adhesion, cell viability, and expression of neural differentiation markers. The morphology of rADSCs grown on conductive patterned scaffolds noticeably was significantly different from that of stem cells cultivated on flat scaffolds. This difference suggests that the change in cell and nuclear shape imposed by the patterned conductive substrate leads to altered gene expression and neural differentiation of cultured cells. In summary, a conductive chitosanpolyaniline scaffold with biomimetic topography demonstrates a promising method for enhancing the neural differentiation of rADSCs for the treatment of neurodegenerative diseases.

Electrically conductive carbon‐based (bio)‐nanomaterials for cardiac tissue engineering

“… 137 , 138 Likewise, upregulated expression of neural progenitor markers, enhanced cell differentiation toward neurons, and promoted neural induction within conducted substrates have been demonstrated. 139 , 140 , 141 , 142 , 143 Other than neural tissue, muscles' contraction is also followed by an electrical signal propagating throughout the tissue. In cardiac tissue repair, the conductive substrate is in charge of electromechanical and electrochemical transmittance leading to electrical stimulation of cells.…”

“…Data transfer is conducted by an action potential within neural networks, requiring a conductive substrate 137,138 . Likewise, upregulated expression of neural progenitor markers, enhanced cell differentiation toward neurons, and promoted neural induction within conducted substrates have been demonstrated 139–143 . Other than neural tissue, muscles' contraction is also followed by an electrical signal propagating throughout the tissue.…”

Conductive Polymeric-Based Electroactive Scaffolds for Tissue Engineering Applications: Current Progress and Challenges from Biomaterials and Manufacturing Perspectives

“…Eftekhari et al did the fabrication of the scaffold using a different conductive polymer of PANI [ 129 ]. PANI was blended with CS to produce a conductive scaffold in the form of cell-imprinted hydrogel on the differentiation of mouse adipose-derived stem cells (rADSCs) into neuron-like cells.…”

“…The mechanical properties of the scaffolds used for neural tissue engineering should mimic the mechanical properties of the ECM to promote the neural differentiation of cells. Physical cues are an important factor in designing an artificial ECM to guide cells because according to the mechanical properties of stem cells, niches can regulate cell behaviour such as attachment, migration, and differentiation [ 129 ]. The use of conductive polymers in electroactive scaffolds can decrease and increase the mechanical properties of the scaffold.…”