One-dimensional migration of olfactory ensheathing cells on synthetic materials: Experimental and numerical characterization

Olfactory ensheathing cells (OECs) are of great interest for regenerative purposes since they are believed to aid axonal growth. With the view set on the strategies to achieve reconnection between neuronal structures, it is of great importance to characterize the behaviour of these cells on long thread-like structures that may efficiently guide cell spread in a targeted way. Here, rat OECs were studied on polycaprolactone (PCL) long monofilaments, on long bars and on discs. PCL turns out to be an excellent substrate for OECs. The cells cover long distances along the monofilaments and colonize completely these struc- tures. With the help of a one-dimensional (1D) analytical model, a migration coefficient, a net proliferation rate constant and the fraction of all cells which undergo migration were obtained. The separate effect of the three phenomena summarized by these parameters on the colo- nization patterns of the 1D path was qualitatively dis- cussed. Other features of interest were also determined, such as the speed of the advance front of colonization and the order of the kinetics of net cell proliferation. Charac- terizing migration by means of these quantities may be useful for comparing and predicting features of the colo- nization process (such as times, patterns, advance fronts and proportion of motile cells) of different cell substrate combinations.Support of the Spanish Science & Innovation Ministery through project MAT2008-06434 is acknowledged. MMP and CMR acknowledge partial funding through the "Convenio de Colaboracion para la Investigacion Basica y Traslacional en Medicina Regenerativa" between the Instituto Nacional de Salud Carlos III, the Conselleria de Sanidad of the Generalitat Valenciana and the Foundation Centro de Investigacion Principe Felipe.Perez Garnes, M.; Martínez Ramos, C.; Barcia, JA.; Escobar Ivirico, JL.; Gomez Pinedo, UA.; Vallés Lluch, A.; Monleón Pradas, M. (2013). One-dimensional migration of olfactory ensheathing cells on synthetic materials: Experimental and numerical characterization. Cell Biochemistry and Biophysics. 65:21-36. https://doi.org/10.1007/s12013-012-9399-1S213665Stokols, S., Sakamoto, J., Breckon, C., Holt, T., Weiss, J., & Tuszynski, M. H. (2006). Templated agarose scaffolds support linear axonal regeneration. Tissue Engineering, 12(10), 2777–2787.Wei, Y. T., Tian, W. M., Yu, X., Cui, F. Z., Hou, S. P., Xu, Q. Y., et al. (2007). Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain. Biomedical Materials, 2(3), 142–146.Yao, L., Wang, S., Cui, W., Sherlock, R., O’Connell, C., Damodaran, G., et al. (2009). Effect of functionalized micropatterned PLGA on guided neurite growth. Acta Biomaterialia, 5(2), 580–588.Chehrehasa, F., Windus, L. C. E., Ekberg, J. A. K., Scott, S. E., Amaya, D., Mackay-Sim, A., et al. (2010). Olfactory glia enhance neonatal axon regeneration. Molecular and Cellular Neuroscience, 45(3), 277–288.Chen, B. K., Knight, A. M., de Ruiter, G. C., Spinner, R. J., Yaszemski, M. J., Currier, B. L., et al. (2009). Axon regeneration through scaffold into distal spinal cord after transection. Journal of Neurotrauma, 26(10), 1759–1771.Goto, E., Mukozawa, M., Mori, H., & Hara, M. (2010). A rolled sheet of collagen gel with cultured Schwann cells: Model of nerve conduit to enhance neurite growth. Journal of Bioscience and Bioengineering, 109(5), 512–518.Lietz, M., Dreesmann, L., Hoss, M., Oberhoffner, S., & Schlosshauer, B. (2006). Neuro tissue engineering of glial nerve guides and the impact of different cell types. Biomaterials, 27(8), 1425–1436.Radtke, C., Sasaki, M., Lankford, K. L., Vogt, P. M., & Kocsis, J. D. (2008). Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury. Journal of Rehabilitation Research and Development, 45(1), 141–151.Wei, Y., Miao, X., Xian, M., Zhang, C., Liu, X., Zhao, H., et al. (2008). Effects of transplanting olfactory ensheathing cells on recovery of olfactory epithelium after olfactory nerve transection in rats. Medical Science Monitor, 14(10), 198–204.Tennent, R., & Chuah, M. I. (1996). Ultrastructural study of ensheathing cells in early development of olfactory axons. Brain Research, Developmental Brain Research, 95(1), 135–139.Doucette, R. (1990). Glial influences on axonal growth in the primary olfactory system. Glia, 3(6), 433–449.Field, P., Li, Y., & Raisman, G. (2003). Ensheathment of the olfactory nerves in the adult rat. Journal of Neurocytology, 32(3), 317–324.Boyd, J. G., Doucette, R., & Kawaja, M. D. (2005). Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord. Faseb Journal, 19(7), 694–703.Franklin, R. J., Gilson, J. M., Franceschini, I. A., & Barnett, S. C. (1996). Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell line into areas of demyelination in the adult CNS. Glia, 17(3), 217–224.Imaizumi, T., Lankford, K. L., Waxman, S. G., Greer, C. A., & Kocsis, J. D. (1998). Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. Journal of Neuroscience, 18(16), 6176–6185.Raisman, G. (2001). Olfactory ensheathing cells - another miracle cure for spinal cord injury? Nature Reviews Neuroscience, 2(5), 369–375.Ramón-Cueto, A., Cordero, M. I., Santos-Benito, F. F., & Avila, J. (2000). Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron, 25(2), 425–435.Chuah, M. I., Choi-Lundberg, D., Weston, S., Vincent, A. J., Chung, R. S., Vickers, J. C., et al. (2004). Olfactory ensheathing cells promote collateral axonal branching in the injured adult rat spinal cord. Experimental Neurology, 185(1), 15–25.Bellamkonda, R. V. (2006). Peripheral nerve regeneration: An opinion on channels, scaffolds and anisotropy. Biomaterials, 27(19), 3515–3518.Liu, Y., Gong, Z., Liu, L., & Sun, H. (2010). Combined effect of olfactory ensheathing cell transplantation and glial cell line-derived neurotrophic factor (GDNF) intravitreal injection on optic nerve injury in rats. Molecular Vision, 16, 2903–2910.Zhu, Y., Cao, L., Su, Z., Mu, L., Yuan, Y., Gao, L., et al. (2010). Olfactory ensheathing cells: Attractant of neural progenitor migration to olfactory bulb. Glia, 58(6), 716–729.Basiri, M., & Doucette, R. (2010). Sensorimotor cortex aspiration: A model for studying Wallerian degeneration-induced glial reactivity along the entire length of a single CNS axonal pathway. Brain Research Bulletin, 81(1), 43–52.Li, Y., Carlstedt, T., Berthold, C.-H., & Raisman, G. (2004). Interaction of transplanted olfactory-ensheathing cells and host astrocytic processes provides a bridge for axons to regenerate across the dorsal root entry zone. Experimental Neurology, 188(2), 300–308.Li, Y., Yamamoto, M., Raisman, G., Choi, D., & Carlstedt, T. (2007). An experimental model of ventral root repair showing the beneficial effect of transplanting olfactory ensheathing cells. Neurosurgery, 60(4), 734–741.Ramón-Cueto, A., Plant, G. W., Avila, J., & Bunge, M. B. (1998). Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. The Journal of Neuroscience, 18(10), 3803–3815.Gómez-Pinedo, U., Vidueira, S., Sancho, F. J., García-Verdugo, J. M., Matías-Guiu, J., & Barcia, J. A. (2011). Olfactory ensheathing glia enhances reentry of axons into the brain from peripheral nerve grafts bridging the substantia nigra with the striatum. Neuroscience Letters, 494(2), 104–108.Graziadei, P. P., Levine, R. R., & Graziadei, G. A. (1978). Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice. Proceedings of the National academy of Sciences of the United States of America, 75(10), 5230–5234.Cao, L., Liu, L., Chen, Z. Y., Wang, L. M., Ye, J. L., Qiu, H. Y., et al. (2004). Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair. Brain, 127(3), 535–549.Cao, L., Su, Z., Zhou, Q., Lv, B., Liu, X., Jiao, L., et al. (2006). Glial cell line-derived neurotrophic factor promotes olfactory ensheathing cells migration. Glia, 54(6), 536–544.Woodhall, E., West, A. K., & Chuah, M. I. (2001). Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors. Brain Research. Molecular Brain Research, 88(1–2), 203–213.Cao, L., Zhu, Y. L., Su, Z., Lv, B., Huang, Z., Mu, L., et al. (2007). Olfactory ensheathing cells promote migration of Schwann cells by secreted nerve growth factor. Glia, 55(9), 897–904.Doucette, R. (1996). Immunohistochemical localization of laminin, fibronectin and collagen type IV in the nerve fiber layer of the olfactory bulb. International Journal of Developmental Neuroscience, 14(7–8), 945–959.Franceschini, I. A., & Barnett, S. C. (1996). Low-affinity NGF-receptor and E-N-CAM expression define two types of olfactory nerve ensheathing cells that share a common lineage. Developmental Biology, 173(1), 327–343.Runyan, S. A., & Phelps, P. E. (2009). Mouse olfactory ensheathing glia enhance axon outgrowth on a myelin substrate in vitro. Experimental Neurology, 216(1), 95–104.Shen, Y., Qian, Y., Zhang, H., Zuo, B., Lu, Z., Fan, Z., et al. (2010). Guidance of olfactory ensheathing cell growth and migration on electrospun silk fibroin scaffolds. Cell Transplantation, 19(2), 147–157.Li, B.-C., Jiao, S.-S., Xu, C., You, H., & Chen, J.-M. (2010). PLGA conduit seeded with olfactory ensheathing cells for bridging sciatic nerve defect of rats. Journal of Biomedical Materials Research, Part A, 94(3), 769–780.Clements, I. P., Kim, Y. T., English, A. W., Lu, X., Chung, A., & Bellamkonda, R. V. (2009). Thin-film enhanced nerve guidance channels for peripheral nerve repair. Biomaterials, 30(23–24), 3834–3846.Martín-López, E., Nieto-Díaz, M., & Nieto-Sampedro, M. (2012). Differential adhesiveness and neurite-promoting activity for neural cells of chitosan, gelatin, and poly-l-lysine films. Journal of Biomaterials Applications, 26(7), 791–809.Cai, J., Peng, X., Nelson, K. D., Eberhart, R., & Smith, G. M. (2005). Permeable guidance channels containing microfilament scaffolds enhance axon growth and maturation. Journal of Biomedical Material Research Part A, 75(2), 374–386.Novikova, L. N., Mosahebi, A., Wiberg, M., Terenghi, G., Kellerth, J. O., & Novikov, L. N. (2006). Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation. Journal of Biomedical Materials Research, Part A, 77(2), 242–252.Tang, Z. P., Liu, N., Li, Z. W., Xie, X. W., Chen, Y., Shi, Y. H., et al. (2010). In vitro evaluation of the compatibility of a novel collagen-heparan sulfate biological scaffold with olfactory ensheathing cells. Chinese Medical Journal (English), 123(10), 1299–1304.Wang, B., Zhao, Y., Lin, H., Chen, B., Zhang, J., Zhang, J., et al. (2006). Phenotypical analysis of adult rat olfactory ensheathing cells on 3-D collagen scaffolds. Neuroscience Letters, 401(1–2), 65–70.Guarnieri, D., De Capua, A., Ventre, M., Borzacchiello, A., Pedone, C., Marasco, D., et al. (2010). Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters. Acta Biomaterialia, 6(7), 2532–2539.Ngo, T. T., Waggoner, P. J., Romero, A. A., Nelson, K. D., Eberhart, R. C., & Smith, G. M. (2003). Poly(l-lactide) microfilaments enhance peripheral nerve regeneration across extended nerve lesions. Journal of Neuroscience Research, 72(2), 227–238.Schnell, E., Klinkhammer, K., Balzer, S., Brook, G., Klee, D., Dalton, P., et al. (2007). Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-e-caprolactone and a collagen/poly-e-caprolactone blend. Biomaterials, 28(19), 3012–3025.Lim, S. H., Liu, X. Y., Song, H., Yarema, K. J., & Mao, H. Q. (2010). The effect of nanofiber-guided cell alignment on the preferential differentiation of neural stem cells. Biomaterials, 31(34), 9031–9039.Wong, D. Y., Hollister, S. J., Krebsbach, P. H., & Nosrat, C. (2007). Poly(epsilon-caprolactone) and poly (l-lactic-co-glycolic acid) degradable polymer sponges attenuate astrocyte response and lesion growth in acute traumatic brain injury. Tissue Engineering, 13(10), 2515–2523.Wong, D. Y., Krebsbach, P. H., & Hollister, S. J. (2008). Brain cortex regeneration affected by scaffold architectures. Journal of Neurosurgery, 109(4), 715–722.Wong, D. Y., Leveque, J. C., Brumblay, H., Krebsbach, P. H., Hollister, S. J., & Lamarca, F. (2008). Macro-architectures in spinal cord scaffold implants influence regeneration. Journal of Neurotrauma, 25(8), 1027–1037.Pierucci, A., de Duek, E. A., & de Oliveira, A. L. (2008). Peripheral nerve regeneration through biodegradable conduits prepared using solvent evaporation. Tissue Engineering Part A, 14(5), 595–606.Vleggeert-Lankamp, C. L., de Ruiter, G. C., Wolfs, J. F., Pego, A. P., van den Berg, R. J., Feirabend, H. K., et al. (2007). Pores in synthetic nerve conduits are beneficial to regeneration. Journal of Biomedical Material Research Part A, 80(4), 965–982.Cai, A. Q., Landman, K. A., & Hughes, B. D. (2007). Multi-scale modeling of a wound-healing cell migration assay. Journal of Theoretical Biology, 245(3), 576–594.Maini, P. K., McElwain, D. L., & Leavesley, D. I. (2004). Traveling wave model to interpret a wound-healing cell migration assay for human peritoneal mesothelial cells. Tissue Engineering, 10(3–4), 475–482.Dokukina, I. V., & Gracheva, M. E. (2010). A model of fibroblast motility on substrates with different rigidities. Biophysical Journal, 98(12), 2794–2803.Schneider, I. C., & Haugh, J. M. (2004). Spatial analysis of 3′ phosphoinositide signaling in living fibroblasts: II. Parameter estimates for individual cells from experiments. Biophysical Journal, 86(1), 599–608.Marcy, Y., Prost, J., Carlier, M.-F., & Sykes, C. C. (2004). Forces generated during actin-based propulsion: A direct measurement by micromanipulation. Proceedings of the National academy of Sciences of the United States of America, 101(16), 5992–5997.Mogilner, A., & Oster, G. (2003). Polymer motors: Pushing out the front and pulling up the back. Current Biology, 13(18), R721–R733.Cheng, G., Youssef, B. B., Markenscoff, P., & Zygourakis, K. (2006). Cell population dynamics modulate the rates of tissue growth processes. Biophysical Journal, 90(3), 713–724.Galbusera, F., Cioffi, M., Raimondi, M. T., & Pietrabissa, R. (2007). Computational modeling of combined cell population dynamics and oxygen transport in engineered tissue subject to interstitial perfusion. Computer Methods Biomechanics and Biomedical Engineering, 10(4), 279–287.Hatzikirou, H., & Deutsch, A. (2008). Cellular automata as microscopic models of cell migration in heterogeneous environments. Current Topics in Developmental Biology, 81, 401–434.Reffay, M., Petitjean, L., Coscoy, S., Grasland-Mongrain, E., Amblard, F., Buguin, A., et al. (2011). Orientation and polarity in collectively migrating cell structures: Statics and dynamics. Biophysical Journal, 100(11), 2566–2575.Chung, C. A., Yang, C. W., & Chen, C. W. (2006). Analysis of cell growth and diffusion in a scaffold for cartilage tissue engineering. Biotechnology and Bioengineering, 94(6), 1138–1146.Dunn, J. C., Chan, W. Y., Cristini, V., Kim, J. S., Lowengrub, J., Singh, S., et al. (2006). Analysis of cell growth in three-dimensional scaffolds. Tissue Engineering, 12(4), 705–716.Harms, B. D., Bassi, G. M., Horwitz, A. R., & Lauffenburger, D. A. (2005). Directional persistence of EGF-induced cell migration is associated with stabilization of lamellipodial protrusions. Biophysical Journal, 88(2), 1479–1488.Lemon, G., & King, J. (2007). Travelling-wave behaviour in a multiphase model of a population of cells in an artificial scaffold. Journal of Mathematical Biology, 55(4), 449–480.Fisher, R. (1937). The wave of advance of advantageous genes. Annals of Eugenics, 7, 355–369.Graner, F.o., & Glazier, J. A. (1992). Simulation of biological cell sorting using a two-dimensional extended Potts model. Physical Review Letters, 69(13), 2013–2016.Ouaknin, G. Y., & Bar-Yoseph, P. Z. (2009). Stochastic collective movement of cells and fingering morphology: No maverick cells. Biophysical Journal, 97(7), 1811–1821.Savill, N. J., & Hogeweg, P. (1997). Modelling morphogenesis: From single cells to crawling slugs. Journal of Theoretical Biology, 184(3), 229–235.Brockes, J. P., Fields, K. L., & Raff, M. C. (1979). Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Research, 165, 105–118.Selinummi, J., Seppala, J., Yli-Harja, O., & Puhakka, J. A. (2005). Software for quantification of labeled bacteria from digital microscope images by automated image analysis. BioTechniques, 39(6), 859–863.Gupta, D., Venugopal, J., Prabhakaran, M. P., Dev, V. R., Low, S., Choon, A. T., et al. (2009). Aligned and random nanofibrous substrate for the in vitro culture of Schwann cells for neural tissue engineering. Acta Biomaterialia, 5(7), 2560–2569.Nisbet, D. R., Yu, L. M., Zahir, T., Forsythe, J. S., & Shoichet, M. S. (2008). Characterization of neural stem cells on electrospun poly(epsilon-caprolactone) submicron scaffolds: Evaluating their potential in neural tissue engineering. Journal of Biomaterials Science, Polymer Edition, 19(5), 623–634.Huang, Z. H., Wang, Y., Cao, L., Su, Z. D., Zhu, Y. L., Chen, Y. Z., et al. (2008). Migratory properties of cultured olfactory ensheathing cells by single-cell migration assay. Cell Research, 18, 479–490.Ekberg, J. A. K., Amaya, D., Mackay-Sim, A., & St. John, J. A. (2012). The migratory of olfactory ensheathing cells during development and regeneration. Neurosignals. doi: 10.1159/000330895 .Ruitenberg, M. J., Vukovic, J., Sarich, J., Busfield, S. J., & Plant, G..W. (2006). Olfactory ensheathing cells: characteristics, genetic engineering, and therapeutic potential. Journal of Neurotrauma, 23, 468–478.Chaikin, P. M., & Lubensky, T. C. (1995). Principles of condensed matter physics (p. 371). Cambridge, UK: Cambridge University Press.Simpson, M. J., Landman, K. A., & Hughes, B. D. (2010). Cell invasion with proliferation mechanisms motivated by time-lapse data. Physica A, 389, 3779–3790

Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

<p>Abstract</p> <p>Background</p> <p>Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke.</p> <p>Methods</p> <p>BALB/Ca-RAG2^-/-γc^-/-mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM.</p> <p>Results</p> <p>In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation.</p> <p>Conclusions</p> <p>Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2^-/-γC ^-/-allows cell transplant from different species, even human, to be analyzed.</p

Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

Background: Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke. Methods: BALB/Ca-RAG2-/-gc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM. Results: In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation. Conclusions: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2-/- gC -/- allows cell transplant from different species, even human, to be analyzed

Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice

Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) γC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 × 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok

Neural tissue regeneration in experimental brain injury model with channeled scaffolds of acrylate copolymers

The objective of the present study was to evaluate the biocompatibility and cell hosting ability of a copolymer scaffold based on ethyl acrylate (EA) and hydroxyl ethyl acrylate (HEA) in vivo after an experimental brain injury. Wistar rats were subjected to cryogenic traumatic brain injury. We evaluated the tissue response to the implanted materials after 8 weeks. The materials were implanted devoid of cells; they provoked a minimal scar response by the host tissue and permitted the invasion of neurons and glia inside them. We also found new blood vessels surrounding and inside the implant. Thus, the copolymer scaffold proves to offer a suitable environment producing a cellular network potentially useful in brain repair after brain injury.CMR, JAB, UGP, and MMP acknowledge financing through projects MAT2011-28791-C03-01 and MAT2011-28791-C03-02 and ERA-NET NEURON project PRI-PIMNEU-2011-1372. JMSL acknowledges funding through Programa de Ayudas a la Investigacion Cientifica Universidad CEU-Cardenal Herrera (PRCEU-UCH 34/12, PRCEU-UCH 38/10) and Programa CEU-Santader ayudas a grupos consolidados 2014-2015.Martínez Ramos, C.; Gomez Pinedo, UA.; Garcia Esparza, MÁ.; Soria Lopez, JM.; Barcia Albacar, JA.; Monleón Pradas, M. (2015). Neural tissue regeneration in experimental brain injury model with channeled scaffolds of acrylate copolymers. Neuroscience Letters. 598:96-101. https://doi.org/10.1016/j.neulet.2015.05.021S9610159