title: Immunomodulatory and angiogenic responses induced by graphene oxide scaffolds in chronic spinal hemisected rats.
abstract: Attractive physic-chemical features of graphene oxide (GO) and promising results in vitro with neural cells encourage its exploration for biomedical applications including neural regeneration. Fueled by previous findings at the subacute state, we herein investigate for the first time chronic tissue responses (at 30 days) to 3D scaffolds composed of partially reduced GO (rGO) when implanted in the injured rat spinal cord. These studies aim to define fibrotic, inflammatory and angiogenic changes at the lesion site induced by the chronic implantation of these porous structures. Injured animals receiving no scaffolds show badly structured lesion zones and more cavities than those carrying rGO materials, thus pointing out a significant role of the scaffolds in injury stabilization and sealing. Notably, GFAP(+) cells and pro-regenerative macrophages are evident at their interface. Moreover, rGO scaffolds support angiogenesis around and, more importantly, inside their structure, with abundant and functional new blood vessels in whose proximities inside the scaffolds some regenerated neuronal axons are found. On the contrary, lesion areas without rGO scaffolds show a diminished quantity of blood vessels and no axons at all. These findings provide a foundation for the usefulness of graphene-based materials in the design of novel biomaterials for spinal cord repair and encourage further investigation for the understanding of neural tissue responses to this kind of materials in vivo.
authors.affiliation: Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Finca la Peraleda s/n, 45071, Toledo, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: López-Dolado
authors.affiliation: Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Finca la Peraleda s/n, 45071, Toledo, Spain.
authors.forename: Ankor
authors.initials: A
authors.lastname: González-Mayorga
authors.affiliation: Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), C/Sor Juana Inés de la Cruz 3, 28049, Madrid, Spain.
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Gutiérrez
authors.affiliation: Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Finca la Peraleda s/n, 45071, Toledo, Spain. Electronic address: mslopezterradas@sescam.jccm.es.
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Serrano
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use; D006108:Graphite / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D056747:Immunomodulation; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000473:pathology*; D010087:Oxides / Q000737:chemistry / Q000627:therapeutic use*; D017208:Rats, Wistar; D012038:Regeneration; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology; D013119:Spinal Cord Injuries / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D058630:Spinal Cord Regeneration; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D043925:Angiogenesis Inducing Agents; D001672:Biocompatible Materials; D010087:Oxides; D006108:Graphite
keywords: Angiogenesis; Graphene oxide; Macrophage; Scaffold; Spinal cord injury