Conductive scaffolds for guided neural network formation

Background:

The present invention relates to the fabrication of patterned conductive scaffolds of micro and/or nanofibers with the help of printing techniques (e.g., near-field electrostatic printing, inkjet printing) and the formation of two-dimensional (2D) or three-dimensional (3D) neural networks guided by the conductive patterns under electrical stimulation to mimic the native counterparts. Applications of such patterned conductive scaffolds include but not limited to engineered conduits for guiding the differentiation and outgrowth of neural cells in peripheral nerve damage or in large-volume spinal cord injury under the electrical stimulation. Meanwhile, the scaffolds could also locally deliver various biomolecules in conjunction with electrical stimulation for facilitated nervous system regeneration.

Summary:

In conjunction with inkjet printing and near-field electrostatic printing (NFEP), patterned conductive scaffolds can be generated either on electrospun matrices or 3D microfiber scaffolds upon layer-by-layer assembly of graphene oxide and reduction into reduced graphene oxide. Onto such patterned conductive scaffolds, 2D or 3D neural network with a similar pattern can be formed under electrical stimulation. Meanwhile, such patterned conductive scaffolds have a high degree of freedom, a relatively low barrier for processing, and strong error-tolerance during manufacturing.

The patterned conductive scaffolds of the present invention can serve as engineered conduits for guiding the differentiation and outgrowth of neural cells for the treatment of peripheral nerve damage or large-volume spinal cord injury under the electrical stimulation. The scaffolds could also locally deliver various biomolecules in conjunction with electrical stimulation for facilitated nervous system regeneration. More specifically, 2D conductive scaffolds/membranes can be further fabricated into a nerve conduit or nerve grafts using sheet rolling, matrix molding, and other bio-manufacturing approaches and used for facilitated nerve regeneration under electrical stimulation. 3D microfiber conductive scaffolds (e.g., those derived from near-field electrostatic printing) can be utilized for advanced nerve repair via capture of anatomical accuracy and complex geometries, as well as through programmable incorporation of biomimetic physical and biochemical functionalities in conjunction with electrical stimulation. With the aid of advanced, patient-specific scanning technology (e.g., magnetic resonance imaging and computed tomography), this approach has the potential to produce customized biomedical devices that possess the geometries to match inherent tissue anatomies. Besides nervous repair, the conductive scaffolds made in accordance with embodiments of the present invention may also see potential applications in bone, chronic wounds, muscle, cardiac and vascular repair, as 2D matrices or 3D constructs.
 

Benefits:

• Ready fabrication processes of 2D and 3D patterned conductive scaffolds with demonstrated computer-aided biofabrication.
• The conductive scaffolds of rGO coated microfibers or rGO-patterned fibrous matrices not only enable the spatial organization of neural cells but also guide the differentiation into the neural network under the electrical stimulation.
• Providing localized electrical stimulation to neuron cells and guiding the controllable formation of neural networks, which can maximally mimic their native counterparts.
• The patterned conductive scaffolds exhibit broader application potentials (e.g., wearable devices, engineered conduits, drug delivery systems, 2D and 3D tissue regeneration scaffolds for bone, chronic wounds and muscles) with mass-production capability.

Applications:

• Nerve regeneration
• Neural engineering
• Muscle regeneration
• Bone regeneration
• Chronic wound repair

Key words:

Electrical stimulation, reduced graphene oxide, neuronal network, microfibers, conductive micropatterns.

Publication:

https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.202004555