Design and synthesis of nano-biomaterials based on graphene and local delivery of cerebrolysin into the injured spinal cord of mice, promising neural restoration

Abstract

Spinal cord injury (SCI) is an incurable and catastrophic health issue with no clinical solution. As part of cascade reactions, the inflammatory process and fibrous glial scar production aggravate the amount of lesion through a secondary damage mechanism, encouraging scientists from other disciplines to investigate new paths for solving this problem. Graphene oxide (GO) and its derivatives are among the most promising biomedical and nerve tissue regeneration materials due to their remarkable chemical, mechanical, and electrical properties. This paper designs and introduces a new GO-based nanomaterial to minimize inflammation and stimulate neurite regrowth. To improve biocompatibility, biodegradability, and cell proliferation, GO plates were modified with polyethylene glycol (PEG) and Au nanoparticles as neuroprotective and antibacterial agents, respectively. Preliminary biological investigations on bone marrow derived mesenchymal stem cells (BM-MSCs) with various concentrations of a graphenic nanocarrier indicated a lack of cell toxicity and an enhancement in BM-MSC proliferation of about 10% after 48 hours. Therapeutic nanostructures were used in the T10 segment of a mouse SCI model. The pathological and immunohistochemical data revealed that refilling tissue cavities, decreasing degeneration, and establishing neuroregeneration resulted in a considerable improvement of hind limb motor function. Furthermore, compared to the nanocomposite mixture alone, the intraspinal delivery of cerebrolysin (CRL) had a more satisfying impact on nerve regrowth, cystic cavity, hemorrhage avoidance, and motor function enhancement. This study demonstrates the potential of graphenic nanomaterials for SCI treatment and neuroregeneration applications.