Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells

Abstract

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine-modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDAincorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural-like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.

Strategy for Designing a Cell Scaffold to Enable Wireless Electrical Stimulation for Enhanced Neuronal Differentiation of Stem Cells

“…[5,6] Thus, several studies have been focused on the use of conductive scaffolds, including conductive-polymer-based and carbonmaterial-based scaffolds, for nerve tissue engineering. [7][8][9] Among them, the use of graphene scaffolds has rapidly increased in biomedicine because of the unique structure, large specific surface area, favorable biocompatibility, and excellent electrical conductivity of graphene. [10][11][12][13] Moreover, graphene scaffolds perform an active role in directing the differentiation of neural stem cells (NSCs) and reinforcing electrical signaling in neural networks.…”

Engineering the MSC Secretome: A Hydrogel Focused Approach

“…MSCs have been shown to respond to electrical stimulation resulting in changes in cell morphology and fate. [ 128,129 ] Employed use of conductive substrates with hydrogels, [ 130 ] conductive composites, [ 131 ] and conductive polymers [ 132 ] for MSC culture has shown great promise for applications in cardiac, bone, and neural tissue engineering. While the effects of mechanical and electrical stimulation on the MSC secretome has not been explored, combinatorial approaches must be utilized to elucidate cellular responses to multiple biophysical cues to recapitulate the in vivo environment.…”

Flexible Polydopamine Bioelectronics

“…Similarly, this strategy can be extended to other carbon‐based materials such as graphene and GO, [ 84 ] metal nanomaterials, [ 85 ] and black phosphorus. [ 86 ]…”