Two-Dimensional Materials for Tissue Engineering and Neural Interfacing Applications

Abstract

The pages of a book behave very strangely compared to a block of wood - two-dimensional (2D) nanomaterials are no different. Offering unique properties that differ from their bulk counterparts, this simple change in dimensionality unlocks a world of applications that has the potential to revolutionize biomedical research. In this thesis, I explore some of these extraordinary properties, demonstrating how they may be harnessed to advance nerve and bone regeneration strategies, and to create innovative neural interfacing devices. Focusing primarily on graphene and 2D boron, this work showcases the wide-reaching impact of these versatile materials. In Chapter 2, graphene was applied to the challenge of neuronal medical device development, with a focus on neuronal regeneration using electrical stimulation. A soft, electrically conductive, and biocompatible collagen-graphene composite material (NeuroGraph) was developed, with diverse fabrication capabilities into scaffolds, microneedles, and bioelectronic circuits. Electrical stimulation on NeuroGraph substrates led to a significant enhancement in neurite outgrowth and cellular morphology, demonstrating its potential as a promising platform material for electroconductive tissue regeneration. Building on this, in Chapter 3 the graphene formulation was further refined for biocompatibility and conductivity, and a flexible, biocompatible polymer-graphene composite system was developed by combining the graphene formulation with polycaprolactone (PolyGraph). The electrochemical properties of this material were enhanced by surface roughening with NaOH, and coating with conductive AuPd. This enabled the creation of flexible, high-performance microelectrode neural interfaces with significant potential for applications in both electrical stimulation therapies and bidirectional neural interfacing. Finally, demonstrating the breadth of possibilities in the field of 2D materials, in Chapter 4 boron nanoplatelets exfoliated from a non-layered precursor using liquid-phase exfoliation were combined with collagen to form collagen-boron (BColl) scaffolds. By leveraging the 2D morphology of the nanoplatelets alongside the intrinsic bioactivity of boron and support of a collagen matrix with tailored characteristics for bone repair, these scaffolds were shown to enhance osteogenesis, angiogenesis, and neurogenesis, all while preventing infection, inflammation, and stiffness mismatch. Taken together, these results showcase boron's potential to offer multifunctional benefits to clinically relevant aspects of next-generation bone biomaterial development. Though this work represents only a microcosm of the immense potential that 2D nanomaterials hold for biomedical applications, the findings presented herein highlight key challenges and opportunities within the field. The versatility of these materials presents a promising vision for future devices and treatments, smoothing the trade-off between physicochemical and biological properties. As our understanding of the nanoscale world and the complex interplay between it and the vast landscape of regenerative medicine and neural interfacing deepens, these materials could fundamentally reshape how we approach regeneration and augmentation.