No abstract

The increasing prevalence and high sanitary costs of lesions affecting the central nervous system (CNS) at the spinal cord are encouraging experts in different fields to explore new avenues for neural repair. In this context, graphene and its derivatives are attracting significant attention, although their toxicity and performance in the CNS in vivo remains unclear. Here, the subacute tissue response to 3D flexible and porous scaffolds composed of partially reduced graphene oxide is investigated when implanted in the injured rat spinal cord. The interest of these structures as potentially useful platforms for CNS regeneration mainly relies on their mechanical compliance with neural tissues, adequate biocompatibility with neural cells in vitro and versatility to carry topographical and biological guidance cues. Early tissue responses are thoroughly investigated locally (spinal cord at C6 level) and in the major organs (i.e., kidney, liver, lung, and spleen). The absence of local and systemic toxic responses, along with the positive signs found at the lesion site (e.g., filler effect, soft interface for no additional scaring, preservation of cell populations at the perilesional area, presence of M2 macrophages), encourages further investigation of these materials as promising components of more efficient material-based platforms for CNS repair.

Graphene oxide (GO) assists a diverse set of promising routes to build bioactive neural microenvironments by easily interacting with other biomaterials to enhance their bulk features or, alternatively, self-assembling toward the construction of biocompatible systems with specific three-dimensional (3D) geometries. Herein, we first modulate both size and available oxygen groups in GO nanosheets to adjust the physicochemical and biological properties of polycaprolactone–gelatin electrospun nanofibrous systems. The results show that the incorporation of customized GO nanosheets modulates the properties of the nanofibers and, subsequently, markedly influences the viability of neural progenitor cell cultures. Interestingly, the partially reduced GO (rGO) nanosheets with larger dimensions trigger the best cell response, while the rGO nanosheets with smaller size provoke an accentuated decrease in the cytocompatibility of the resulting electrospun meshes. Then, the most auspicious nanofibers are synergistically accommodated onto the surface of 3D-rGO heterogeneous porous networks, giving rise to fibrous-porous combinatorial architectures suitable for enhancing adhesion and differentiation of neural cells. By varying the chemical composition of the nanofibers, it is possible to adapt their performance as physical crosslinkers for the rGO sheets, leading to the modulation of both pore size and structural/mechanical integrity of the scaffold. Importantly, the biocompatibility of the resultant fibrous-porous systems is not compromised after 14 days of cell culture, including standard differentiation patterns of neural progenitor cells. Overall, in light of these in vitro results, the reported scaffolding approach presents not only an indisputable capacity to support highly viable and interconnected neural circuits but also the potential to unlock novel strategies for neural tissue engineering applications.