PMID- 27214651 OWN - NLM STAT- MEDLINE DCOM- 20180222 LR - 20181005 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 99 DP - 2016 Aug TI - Immunomodulatory and angiogenic responses induced by graphene oxide scaffolds in chronic spinal hemisected rats. PG - 72-81 LID - S0142-9612(16)30179-X [pii] LID - 10.1016/j.biomaterials.2016.05.012 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Lopez-Dolado, Elisa AU - Lopez-Dolado E AD - Hospital Nacional de Paraplejicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Finca la Peraleda s/n, 45071, Toledo, Spain. FAU - Gonzalez-Mayorga, Ankor AU - Gonzalez-Mayorga A AD - Hospital Nacional de Paraplejicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Finca la Peraleda s/n, 45071, Toledo, Spain. FAU - Gutierrez, Maria Concepcion AU - Gutierrez MC AD - Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Cientificas (CSIC), C/Sor Juana Ines de la Cruz 3, 28049, Madrid, Spain. FAU - Serrano, Maria Concepcion AU - Serrano MC AD - Hospital Nacional de Paraplejicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Finca la Peraleda s/n, 45071, Toledo, Spain. Electronic address: mslopezterradas@sescam.jccm.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160510 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Biocompatible Materials) RN - 0 (Oxides) RN - 7782-42-5 (Graphite) SB - IM MH - Angiogenesis Inducing Agents/chemistry/*therapeutic use MH - Animals MH - Axons/metabolism/pathology MH - Biocompatible Materials/chemistry/therapeutic use MH - Graphite/chemistry/*therapeutic use MH - Humans MH - Immunomodulation MH - Male MH - Microscopy, Confocal MH - Microscopy, Electron, Transmission MH - Neurons/*pathology MH - Oxides/chemistry/*therapeutic use MH - Rats, Wistar MH - Regeneration MH - Spinal Cord/blood supply/pathology MH - Spinal Cord Injuries/immunology/pathology/surgery/*therapy MH - Spinal Cord Regeneration MH - Tissue Scaffolds/*chemistry OTO - NOTNLM OT - Angiogenesis OT - Graphene oxide OT - Macrophage OT - Scaffold OT - Spinal cord injury EDAT- 2016/05/24 06:00 MHDA- 2018/02/23 06:00 CRDT- 2016/05/24 06:00 PHST- 2016/03/21 00:00 [received] PHST- 2016/05/02 00:00 [revised] PHST- 2016/05/06 00:00 [accepted] PHST- 2016/05/24 06:00 [entrez] PHST- 2016/05/24 06:00 [pubmed] PHST- 2018/02/23 06:00 [medline] AID - S0142-9612(16)30179-X [pii] AID - 10.1016/j.biomaterials.2016.05.012 [doi] PST - ppublish SO - Biomaterials. 2016 Aug;99:72-81. doi: 10.1016/j.biomaterials.2016.05.012. Epub 2016 May 10.