Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Biomaterials for promoting brain protection, repair and regeneration

Key Points

  • Biomaterials are having an increasingly important role in brain protection, repair and regeneration.

  • Micro and nano-technologies have provided tools that allow cell or tissue transplants to be effectively delivered into the brain.

  • Biomaterial scaffolds placed into the damaged area or cavity potentially provide support for the surrounding brain tissue, function as a substrate for cell growth, axon regeneration and neurite formation, and allow cell infiltration.

  • Biomaterials are being used to promote regeneration and repair of damaged neuronal pathways with stem cell therapies.

  • Current technologies allow greater control over material–cell interactions that mimic specific developmental processes and cellular responses including differentiation, migration and outgrowth.

Abstract

Biomaterials are likely to have an increasingly important role in the treatment of nervous system disorders. Recently developed biomaterials can enable and augment the targeted delivery of drugs or therapeutic proteins to the brain, allow cell or tissue transplants to be effectively delivered to the brain and help to rebuild damaged circuits. Similarly, biomaterials are being used to promote regeneration and to repair damaged neuronal pathways in combination with stem cell therapies. Many of these approaches are gaining momentum because nanotechnology allows greater control over material–cell interactions that induce specific developmental processes and cellular responses including differentiation, migration and outgrowth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The neurovascular unit and the potential of active targeting for drug delivery.
Figure 2: Different technologies for drug delivery into the brain.
Figure 3: Polymer scaffolds can serve several important functions in brain repair processes.

Similar content being viewed by others

References

  1. Pardridge, W. M. Drug targeting to the brain. Pharm. Res. 24, 1733–1744 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Pardridge W. M. Molecular biology of the blood-brain barrier. Mol. Biotechnol. 30, 57–70 (2005). Excellent introduction to the structural and molecular aspects of the blood–brain barrier that limit drug entry into the brain.

    Article  CAS  PubMed  Google Scholar 

  3. Popovic, N. & Brundin, P. Therapeutic potential of controlled drug delivery systems in neurodegenerative disorders. Int. J. Pharm. 314, 120–126 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Silva, G. A. Nanotechnology approaches for the regeneration and neuroprotection of the central nervous system. Surg. Neurol. 63, 301–306 (2005).

    Article  PubMed  Google Scholar 

  5. Halberstadt C and Emerich, D. F. (Eds) Cellular Transplants: From Lab to Clinic. (Academic Press, 2007).

    Google Scholar 

  6. Zhong, Z. & Bellamkonda, R. Biomaterials for the central nervous system. J. R. Soc. Interface 5, 957–975 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pangalos, M. N., Schechter, L. E. & Hurko, O. Drug development for CNS disorders: strategies for balancing risk and reducing attrition. Nature Rev. Drug Discov. 6, 521–532 (2007).

    Article  CAS  Google Scholar 

  8. Pardridge, W. M. The blood-brain barrier: bottleneck in brain development. NeuroRx 2, 3–14 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Neuwelt, E. et al. Strategies to advance translational research into brain barriers. Lancet Oncol. 7, 84–96 (2008). Expert meeting report on essential and high-priority recommendations to propel brain barrier research in different topical areas.

    CAS  Google Scholar 

  10. Weinstein, J. N., Blumenthal, R., Sharrow, S. O. & Henkart, P. A. Antibody mediated targeting of liposomes. Binding to lymphocytes does not ensure incorporation of vesicle contents into the cells. Biochem. Biophys. Acta 509, 272–288 (1978).

    Article  CAS  PubMed  Google Scholar 

  11. Béduneau, A., Saulnier, P. & Benoit, J. P. Active targeting of brain tumors using nanocarriers. Biomaterials 28, 4947–4967 (2007). Introductory review on the use of targeted colloidal systems used for drug delivery to the brain.

    Article  PubMed  CAS  Google Scholar 

  12. Siwak, D. R., Tari, A. M. & Lopez-Berestein, G. The potential of drug-carrying immunoliposomes as anticancer agents. Clin. Cancer Res. 8, 955–956 (2002).

    CAS  PubMed  Google Scholar 

  13. Begley, D. J. Delivery of therapeutic agents to the central nervous system: the problems and the difficulties. Pharmacol. Ther. 104, 29–45 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Denora, N., Trapani, A., Laquintana, V., Lopedota, A. & Trapani, G. Recent advances in medicinal chemistry and pharmaceutical technology strategies for drug delivery to the brain. Curr. Topics Med. Chem. 9, 182–196 (2009).

    Article  CAS  Google Scholar 

  15. Sahoo, S. K. & Labhasetwar, V. Nanotech approaches to drug delivery and imaging. Drug Discov. Today 8, 1112–1120 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Schnyder, A. & Huwyler, J. Drug transport to brain with targeted liposomes. NeuroRx 2, 99–107 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lian, T. & Ho, R. J. Trends and developments in liposome drug delivery systems. J. Pharm. Sci. 90, 667–680 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Misra, A., Ganesh, S., Shahiwala, A. & Shah, S. P. Drug delivery to the central nervous system: a review. J. Pharm. Pharmacol. Sci. 6, 252–273 (2003).

    CAS  Google Scholar 

  19. Allen, T. M. Long-circulating (sterically stabilized) liposomes for targeted drug delivery. Trends Pharmacol. Sci. 15, 215–220 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Pardridge, W. M., Boado, R. J., Black, K. L. & Cancilla, P. A. Blood-brain barrier and new approaches to brain drug delivery. West J. Med. 156, 281–286 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang, Y., Calon, F., Zhu, C., Boado, R. J. & Pardridge, W. M. Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism. Hum. Gene Ther. 14, 1–12 (2003).

    Article  PubMed  Google Scholar 

  22. Lockman, P. R., Mumper, R. J., Khan, M. A. & Allen, D. D. Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev. Ind. Pharm. 28, 1–13 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Kreuter, J. et al. Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm. Res. 20, 409–416 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Menei, P. et al. Intracerebral implantation of NGF-releasing biodegradable microspheres protects striatum against excitotoxic damage. Exper. Neurol. 161, 259–272 (2000).

    Article  CAS  Google Scholar 

  25. Mc Rae, A. & Dahlstrom, A. Transmitter-loaded polymeric microspheres induce regrowth of dopaminergic nerve terminals in striata of rats with 6-OH-DA induced parkinsonism. Neurochem. Int. 25, 27–33 (1994).

    Article  CAS  Google Scholar 

  26. Schubert, D., Dargusch, R., Raitano, J. & Chan S. W. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. 342, 86–91 (2006).

    CAS  Google Scholar 

  27. Blasi, P., Giovagnoli, S., Schoubben, A., Ricci, M. & Rossi, C. Solid lipid nanoparticles for targeted brain drug delivery. Adv. Drug Del. Rev. 59, 454–477 (2007). Interesting introductory review on the potential use of solid-lipid nanoparticles for targeted brain drug delivery.

    Article  CAS  Google Scholar 

  28. Kaur, I. P., Bhandari, R., Bhandari, S. & Kakkar, V. Potential of solid lipid nanoparticles in brain drug targeting. J. Control Rel. 127, 97–109 (2008).

    Article  CAS  Google Scholar 

  29. Brioschi, A. et al. Solid lipid nanoparticles: could they help to improve the efficacy of pharmacologic treatments for brain tumors? Neurol. Res. 29, 324–330 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Chattopadhyay, N. et al. Solid lipid nanoparticles enhance the delivery of the HIV protease inhibitor, atazanavir, by a human brain endothelial cell line. Pharm. Res. 25, 2262–2271 (2008).

    Article  CAS  PubMed  Google Scholar 

  31. Liu, L. et al. Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG-TAT for drug delivery across the blood brain barrier. Biomaterials 29, 1509–1517 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Orive, G. et al. Cell encapsulation: promise and progress. Nature Med. 9, 104–107 (2003). A critical view on cell microencapsulation technology proposed by a panel of experts in the field that summarizes recent progress in the field and outlines what is needed to bring this technology closer to clinical application.

    Article  CAS  PubMed  Google Scholar 

  33. De Vos P. et al. Multiscale requirements for bioencapsulation in medicine and biotechnology. Biomaterials 30, 2559–2570 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Czech, K. A. & Sagen, J. Update on cellular transplantation into the rat CNS as a novel therapy for chronic pain, Prog. Neurobiol., 46, 507–515 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. Lindner, M. D. et al., Somatic delivery of catecholamines in the striatum attenuate parkinsonian symptoms and widen the therapeutic window or oral Sinemet in rats. Exper. Neurol. 14, 130–140 (1997).

    Article  Google Scholar 

  36. Yasuhara, T. et al. Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease. J. Neurosurg. 102, 80–89 (2005).

    Article  PubMed  Google Scholar 

  37. Sajadi A., Bensadoun J. C., Schneider B. L., Lo Bianco C. & Aebischer P. Transient striatal delivery of GDNF via encapsulated cells leads to sustained behavioral improvement in a bilateral model of Parkinson disease. Neurobiol. Dis. 22, 119–129 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Emerich, D. F. et al. Protective effects of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease. Nature 386, 395–399 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Winn, S. R. et al. Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons, Proc. Natl. Acad. Sci. USA, 91, 23–28 (1994).

    Article  Google Scholar 

  40. Tan, S. A. et al. Rescue of motoneurons from axotomy-induced cell death by polymer encapsulated cells genetically engineered to release CNTF. Cell Transpl. 5, 577–587 (1996).

    Article  CAS  Google Scholar 

  41. Visted, T. & Lund-Johansen, M., Progress and challenges for cell encapsulation in brain tumor therapy. Expert Opin. Biol. Ther. 3, 551–561 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Emerich, D. F. et al. Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys. Neurobiol. Dis. 23, 471–480 (2006).

    Article  PubMed  Google Scholar 

  43. Bloch, J. et al. Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study. Hum. Gene Ther. 15, 968–975 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Aebischer, P. et al. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Med. 2, 696–699 (1996). Initial clinical experience using xenogeneic, genetically modified cells to deliver a potentially therapeutic protein.

    Article  CAS  PubMed  Google Scholar 

  45. Zurn, A. D. et al. Evaluation of an intrathecal immune response in amyotrophic lateral sclerosis patients implanted with encapsulated genetically-engineered xenogeneic cells. Cell Transpl. 9, 471–484 (2000).

    Article  CAS  Google Scholar 

  46. Sieving, A. et al. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants Proc. Natl Acad. Sci. USA 103, 3896–3901 (2006). Important demonstration of stable, long-term delivery of CNTF using genetically modified cells transplanted into the vitreous humor.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fitch, M. T., Doller, C., Combs, C. K., Landreth, G. E. & Silver, J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J. Neurosci. 19, 8182–8198 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nomura, H., Tator, C. H. & Shoichet, M. S. Bioengineered strategies for spinal cord repair. J. Neurotrauma 23, 496–507 (2006).

    Article  PubMed  Google Scholar 

  49. Geller, H. M. & Fawcett, J. W. Building a bridge: engineering spinal cord repair. Exp. Neurol. 174, 125–136 (2002).

    Article  PubMed  Google Scholar 

  50. Tsai, E. C., Dalton, P. D., Shoichet, M. S. & Tator, C. H. Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection. J. Neurotrauma 21, 789–804 (2004).

    Article  PubMed  Google Scholar 

  51. Piantino, J., Burdick, J. A., Goldberg, D., Langer, R. & Benowitz, L. I. An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Exp. Neurol. 201, 359–367 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Park, K. I., Teng, Y. D. & Snyder, E. Y. The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nature Biotechnol. 20, 1091–1093 (2002). Convincing demonstration that polymer scaffolds can reduce secondary brain tissue loss and support new and target appropriate tissue regeneration.

    Article  CAS  Google Scholar 

  53. Tate, M. C. et al. Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain. Cell Transpl. 11, 283–295 (2002).

    Article  Google Scholar 

  54. Tate, C. C., et al. Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J. Tiss. Engin. Regen. Med. Feb. 19 Epub (2009).

  55. Lee, Y. L. & Mooney, D. J. Cell-Interactive Polymers for Tissue Engineering. Fibers and Polymers 2, 51–57 (2001).

    Article  CAS  Google Scholar 

  56. Misra, A., Ganesh, S., Shahiwala, A. & Shah, S. P. Drug delivery to the central nervous system: a review. J. Pharm. Pharmacol. Sci. 6, 252–273 (2003).

    CAS  Google Scholar 

  57. Wong, D. Y., Krebsbach, P. H., & Hollister, S. J. Brain cortex regeneration affected by scaffold architectures. J. Neurosurg. 109, 715–722, (2008).

    Article  PubMed  Google Scholar 

  58. Wong, D. Y., Hollister, S. J., Krebsbach, P. H. & Nosrat, C. Poly(ɛ-caprolactone) and poly (L-lactic-co-glycolic acid) degradable polymer sponges attenuate astrocyte response and lesion growth in acute traumatic brain injury. Tissue Engineer. 13, 2515–2523 (2007).

    Article  CAS  Google Scholar 

  59. Zhang, H. et al. Gelatin-siloxane hybrid scaffolds with vascular endothelial growth factor induces brain tissue regeneration. Curr. Neurovasc. Res. 5, 112–117 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Potter, W., Kalil, R. E. & Kao, W. J. Biomimetic material systems for neural progenitor cell-based therapy. Front. Biosci. 13, 806–821, (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Teixeira, A., Duckworth, J. K. & Hermanson, O. Getting the right stuff: controlling neural stem cell state and fate in vivo and in vitro with biomaterials. Cell Res. 17, 56–61 (2007).

    Article  CAS  PubMed  Google Scholar 

  62. Leach, J. K. Multifunctional cell-instructive materials for tissue regeneration; Reg. Med. 1, 447–455 (2006).

    Article  CAS  Google Scholar 

  63. Norman, J. J. & Desai, T. A. Methods for fabrication of nanoscale topography for tissue engineering scaffolds. Ann. Biomed. Eng. 34, 89–101 (2006).

    Article  PubMed  Google Scholar 

  64. Yamada, K. M. & Olden, K. Fibronectins-adhesive glycoproteins of cell surface and blood. Nature 275, 179–184, (1978).

    Article  CAS  PubMed  Google Scholar 

  65. Ruoslahti, E. & Pierschbacher, M. D. Arg-Gly-Asp: a versatile cell recognition signal. Cell 44, 517–518 (1986).

    Article  CAS  PubMed  Google Scholar 

  66. Woerly, S., Pinet, E., de Robertis, L., Van Diep, D. & Bousmina M. Spinal cord repair with PHPMA hydrogel containing RGD peptides (NeurogelTM). Biomaterials 20, 2213–2221 (2001).

    Google Scholar 

  67. Aota, S., Nomizu, M. & Yamada, K. M. The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. J. Biol. Chem. 269, 24756–24761 (1994).

    Article  CAS  PubMed  Google Scholar 

  68. Potter, W., Kalil, R. E. & Kao, W. J. Biomimetic material systems for neural progenitor cell-based therapy. Front. Biosci. 13, 806–821, (2008).

    Article  CAS  PubMed  Google Scholar 

  69. Smyth, N. et al. Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J. Cell Biol. 144, 151–160 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Graf, J. et al. A pentapeptide from the laminin B1 chainmediates cell adhesion and binds the 67, 000 laminin receptor. Biochemistry 26, 6896–6900 (1987).

    Article  CAS  PubMed  Google Scholar 

  71. Jucker, M., Kleinman, H. K. & Ingram, D. K. Fetal rat septal cells adhere to and extend processes on basement membrane, laminin, and a synthetic peptide from the laminin A chain sequence. J. Neurosci. Res. 28, 507–517 (1991).

    Article  CAS  PubMed  Google Scholar 

  72. Yu, T. T. ; &. Shoichet, M. S. Guided cell adhesion and outgrowth in peptide-modified channels for neural tissue engineering. Biomaterials 26, 1507–1514 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Itoh, S. et al. Development of a nerve scaffold using a tendon chitosan tube. Artif. Organs 27, 1079–1088 (2003).

    Article  PubMed  Google Scholar 

  74. Ellis-Behnke, R. G. et al. Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc. Natl Acad. Sci. USA 103, 5054–5059 (2006). Important demonstration that nanoscaffolds foster regeneration. In this study, the optic tract in hamsters regenerated following implantation of a self-assembled nanofibre scaffold resulting in histological and visual recovery.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Nisbet, D. R. et al. Interaction of embryonic cortical neurons on nanofibrous scaffolds for neural tissue engineering. J. Neural Engineer. 4, 35–41 (2007).

    Article  CAS  Google Scholar 

  76. Silva, G. A. et al. Selective differentiation of neural progenitor cells by high epitope density nanofibers. Science 303, 1352–1355 (2004). Important demonstration of the capacity of nanofibres to rapidly and predictably control stem cell differentiation.

    Article  CAS  PubMed  Google Scholar 

  77. Willerth, S. M., Arendas, K. J., Gottlieb, D. I. & Sakiyama Elbert, S. E. Optimization of fibrin scaffolds for differentiation of murine embryonic stem cells into neural lineage cells. Biomaterials 27, 5990–6003 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Brannvall, K. et al. Enhanced neuronal differentiation in a three-dimensional collagen–hyaluronan matrix. J. Neurosci. Res. 85, 2138–2146 (2007).

    Article  CAS  PubMed  Google Scholar 

  79. Bhang, S. H., Lim, J. S., Choi, C. Y., Kwon, Y. K. & Kim, B. S. The behavior of neural stem cells on biodegradable synthetic polymers. J. Biomater. Sci. Polym. Edin. 18, 223–239 (2007).

    Article  CAS  Google Scholar 

  80. Hung, C. H., Lin, Y. L. & Young, T. H. The effect of chitosan and PVDF substrates on the behavior of embryonic rat cerebral cortical stem cells. Biomaterials 27, 4461–4469 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Young, T. H. & Hung, C. H. Behavior of embryonic rat cerebral cortical stem cells on the PVA and EVAL substrates. Biomaterials 26, 4291–4299 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. Kulbatski, I., Mothe, A. J., Nomura, H. & Tator, C. H. Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma. Curr. Drug Targets 6, 111–126 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Levenberg, S. et al. Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds. Proc. Natl Acad. Sci. USA 100, 12741–12746 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Bible, E., Chau, D. Y. S., Alexander, M. R., Price, J., Shakesheff, K. M. & Modo M. The support of neural stem cells transplanted into stroke-induced brain cavities by PLGA particles. Biomaterials 30, 2985–2994 (2009).

    Article  CAS  PubMed  Google Scholar 

  85. Mahoney, M. J. & Saltzman, W. M. Transplantation of brain cells assembled around a programmable synthetic microenvironment. Nature Biotechnol. 19, 934–939 (2001).

    Article  CAS  Google Scholar 

  86. Lu, D., Mahmood, A., Qu, C., Hong, X., Kaplan, D. & Chopp, M. Collagen scaffolds populated with human marrow stromal cells reduce lesion volume and improve functional outcome after traumatic brain injury. Neurosurgery 61, 596–602, (2007).

    Article  PubMed  Google Scholar 

  87. Nomura, H., Tator, C. H. & Shoichet, M. S. Bioengineered strategies for spinal cord repair. J. Neurotrauma 23, 496–507 (2006).

    Article  PubMed  Google Scholar 

  88. Jain, A., Kim, Y. T., McKeon, R. J. & Bellamkonda, R. V. In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. Biomaterials 27, 497–504 (2001).

    Article  CAS  Google Scholar 

  89. Hou, S. et al. The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin. J. Neurosci. Methods 148, 60–70 (2005).

    Article  CAS  PubMed  Google Scholar 

  90. Novikov, L. N. et al. A novel biodegradable implant for neuronal rescue and regeneration after spinal cord injury. Biomaterials 23, 3369–3376 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Kamada T. et al. Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord. J. Neuropathol. Exp. Neurol. 64, 37–45 (2005).

    Article  PubMed  Google Scholar 

  92. Rhodes, K. E. & Fawcett, J. W. Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS? J. Anat. 204, 33–48 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Friedman, J. A. et al. Biodegradable polymer grafts for surgical repair of the injured spinal cord. Neurosurgery 51, 751–752 (2002).

    Google Scholar 

  94. Farokhzad, O. C. & Langer, R. Impact of nanotechnology on drug delivery. ACS Nano. 3, 16–20 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Gu, H., Long, D., Song, C. & Li X. Recombinant human NGF-loaded microspheres promote survival of basal forebrain cholinergic neurons and improve memory impairments of spatial learning in the rat model of Alzheimer's disease with fimbria-fornix lesion. Neurosci Lett 453, 204–209 (2009).

    Article  CAS  PubMed  Google Scholar 

  96. Péan, J. M., Menei, P., Morel, O., Montero-Menei, C. N. & Benoit, J. P. Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons. Biomaterials. 20, 2097–2101 (2000).

    Article  Google Scholar 

  97. Garbayo, E. et al. Effective GDNF brain delivery using microspheres—a promising strategy for Parkinson's disease. J. Control Release 135, 119–126 (2009).

    Article  CAS  PubMed  Google Scholar 

  98. Buchser, E. et al. Immunoisolated xenogeneic chromaffin cell therapy for chronic pain. Initial clinical experience. Anesthesiology 5, 1005–1112 (1996).

    Article  Google Scholar 

  99. Bachoud-Levi, A. C. et al. Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF. Hum. Gene. Ther. 11, 1723–1729 (2000).

    Article  CAS  PubMed  Google Scholar 

  100. Leone, P. et al. Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Ann. Neurol. 48, 27–38 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank L. Sánchez for her assistance in preparing the original figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dwaine F. Emerich.

Ethics declarations

Competing interests

G.O. and E.A are research scientists at the Biotechnology Institute (BTI), Vitoria, Spain. D.F.E. works for InCytu Inc., Lincoln, Rhode Island, USA.

Related links

Related links

DATABASES

OMIM

Alzheimer's disease

amyotrophic lateral sclerosis

Huntington's disease

Parkinson's disease

FURTHER INFORMATION

Neurotech USA press release, March 26th, 2009

NSgene press release, July 4th 2008

Glossary

Proteomics

The large-scale study of proteins, particularly their structures and functions.

Oligonucleotide

A short nucleic-acid polymer, typically with 20 or fewer bases.

Extracellular matrix

(ECM). Connective tissue produced largely by fibroblasts and astrocytes that provides diverse inhibitory and growth promoting signals to neurons and their extensions.

Active targeting

A process whereby the surface of a particle is modified with a ligand so that when injected into the body it can bind to, or target, a specific cell receptor.

Bioavailability

The fraction of an administered dose of drug that reaches the systemic circulation. By definition, when a drug is administered intravenously, its bioavailability is 100%.

Reticuloendothelial system

(RES). Part of the immune system that consists of the phagocytic cells located in reticular connective tissue, primarily monocytes and macrophages.

Immunoliposome

A spherical vesicle consisting of one or more concentric lipid bilayers enclosing one or more aqueous compartments that is coupled to an antibody.

Biodegradable

The chemical breakdown of materials by a physiological environment.

Entrapment

The process of incorporating a drug into a particle, scaffold or device. It is also a measurement to determine and compare the efficiency of drug incorporation.

Covalent link

A bond characterized by the sharing of pairs of electrons between atoms, or between other covalent bonds. In short, attraction-to-repulsion stability that forms between atoms when they share electrons.

Reactive oxygen species

(ROS). Ions or very small molecules that include oxygen ions, free radicals and peroxides, both inorganic and organic. They are highly reactive due to the presence of unpaired valence shell electrons.

Surfactants

Wetting agents that lower the surface tension of a liquid, allowing easier spreading, and that lower the interfacial tension between two liquids.

Amphiphilic block copolymers

Two or more homopolymer subunits linked by covalent bonds with an intermediate non-repeating subunit, known as a junction block. The amphiphilic copolymer has both lipophilic and hydrophilic parts.

Encapsulation

The enclosure of a drug, peptide, cell or any other material within selectively permeable thermoplastics or three-dimensional particles surrounded or not by additional layers.

Thermoplastic

A polymer that turns to a liquid when heated and freezes to a very glassy state when cooled sufficiently.

Glial scar formation (gliosis)

A reactive cellular process involving astrogliosis that occurs after injury to the CNS. The glial scar is the body's mechanism to protect and begin the healing process in the nervous system.

Nanogel

A nanomaterial based on hydrogels of crosslinked polymer network that often combine ionic and non-ionic chains and which enhances the transport of incorporated molecules into the brain.

Cross linking

The joining of adjacent chains of a polymer or protein by creating covalent bonds.

Self assembly

Processes in which a disordered system of pre-existing components forms an organized structure or pattern as a consequence of specific, local interactions among the components themselves, without external direction. An example is the automatic arrangement of phospholipids into a cell wall.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orive, G., Anitua, E., Pedraz, J. et al. Biomaterials for promoting brain protection, repair and regeneration. Nat Rev Neurosci 10, 682–692 (2009). https://doi.org/10.1038/nrn2685

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2685

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing