Peripheral nerve tissue engineering aims to create biomaterials that can replace and possibly even therapeutically surpass the current gold standard nerve autograft. Tissue-engineered constructs can be designed to deliver a combination of benefits to the regenerating nerve, such as supportive cells, alignment, extracellular matrix, soluble factors, and biomechanical integration. An emerging therapeutic opportunity in nerve tissue engineering is the use of electrical stimulation (ES) to modify and enhance therapeutic cell function.
ES has been shown to positively affect four key cell types; neurons, endothelial cells, macrophages, and Schwann cells, involved in peripheral nerve repair1. Briefly, neurons experience faster neurite outgrowth and increased protein adsorption, endothelial cells upregulate angiogenic factors, macrophages may experience a phenotypic shift towards pro-repair phenotype and Schwann cells increase neurotrophic growth factor and exosome secretion. To leverage these phenotypic benefits associated with ES, a conductive tissue engineered scaffold may be used to provide stimulation that improves the regenerative environment, or directly stimulates regenerating axons within the construct. This work attempts to explore how tissue engineering strategies can make use of this therapeutic stimulus to improve nerve regeneration.
A novel conductive tissue engineered construct was developed, comprised of conductive organic semiconducting polypyrrole (PPy) nanoparticles distributed within a cellular or acellular collagen matrix, which is then aligned using gel aspiration ejection (GAE) to generate an engineered neural tissue. The GAE technique has been utilized previously for peripheral nerve tissue engineering of cellular collagen gels2 and has therefore been further developed to provide a rapid method to achieve conductive collagen scaffolds in under 1 hour. A fully hydrated hydrogel is aspirated into a cannula, which simultaneously removes the bulk of the interstitial water within the construct and aligns the fibrous collagen with the construct.
The resultant construct is stabilized through this process and due to the conductive PPy nanoparticles distributed throughout the aligned collagen matrix. The material exhibited conductive properties before and after processing with GAE. The conductive engineered tissue was tested in vitro to assess neural cell compatibility and ability of ES to modulate cell phenotype and regeneration.
ES has provided promsing results to short nerve gap injuries. This approach provides a promising new method for investigating whether ES can be used to enhance nerve tissue engineering, and importantly address clinical need within 'critical length' nerve injury gaps.
- Trueman, R.P., Ahlawat, A.S. & Phillips, J. A shock to the (nervous) system: Bioelectricity within peripheral nerve tissue engineering. Tissue Eng Part B Rev (2021).
- Muangsanit, P. et al. Rapidly formed stable and aligned dense collagen gels seeded with Schwann cells support peripheral nerve regeneration. Journal of Neural Engineering 17, 046036 (2020).