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Biomaterials for Enhancing CNS Repair

  • SI: Present and future of neuroplasticity in CNS recovery
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Abstract

The health of the central nervous system (CNS) does not only rely on the state of the neural cells but also on how various extracellular components organize cellular behaviors into proper tissue functions. Biomaterials have been valuable in restoring or augmenting the roles of extracellular components in the CNS in the event of injury and disease. In this review, we highlight how biomaterials have been enabling tools in important therapeutic strategies involving cell transplantation and drug/protein delivery. We further discuss advances in biomaterial design and applications that can potentially be translated into the CNS to provide unprecedented benefits.

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References

  1. Purushothaman A, Sugahara K, Faissner A. Chondroitin sulfate ‘wobble motifs’ modulate maintenance and differentiation of neural stem cells and their progeny. J Biol Chem. 2012;287:2935–42.

    Article  CAS  PubMed  Google Scholar 

  2. Lang BT et al. Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury. Nature. 2015;518:404–8.

    Article  CAS  PubMed  Google Scholar 

  3. Orive G, Anitua E, Pedraz JL, Emerich DF. Biomaterials for promoting brain protection, repair and regeneration. Nat Rev Neurosci. 2009;10:682–92.

    Article  CAS  PubMed  Google Scholar 

  4. Cooke MJ, Vulic K, Shoichet MS. Design of biomaterials to enhance stem cell survival when transplanted into the damaged central nervous system. Soft Matter. 2010;6:4988.

    Article  CAS  Google Scholar 

  5. Khaing ZZ, Thomas RC, Geissler SA, Schmidt CE. Advanced biomaterials for repairing the nervous system: what can hydrogels do for the brain? Mater Today. 2014;17:332–40.

    Article  CAS  Google Scholar 

  6. Skop NB, Calderon F, Cho CH, Gandhi CD, Levison SW. Improvements in biomaterial matrices for neural precursor cell transplantation. Mol Cell Ther. 2014;2:19.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Park KI, Teng YD, Snyder EY. The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat Biotechnol. 2002;20:1111–7.

    Article  CAS  PubMed  Google Scholar 

  8. Jin K et al. Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats. J Cereb Blood Flow Metab. 2010;30:534–44.

    Article  PubMed  Google Scholar 

  9. Guan J et al. Transplantation of human mesenchymal stem cells loaded on collagen scaffolds for the treatment of traumatic brain injury in rats. Biomaterials. 2013;34:5937–46.

    Article  CAS  PubMed  Google Scholar 

  10. Tate CC et al. Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J Tissue Eng Regen Med. 2009;3:208–17.

    Article  CAS  PubMed  Google Scholar 

  11. Bible E et al. The support of neural stem cells transplanted into stroke-induced brain cavities by PLGA particles. Biomaterials. 2009;30:2985–94.

    Article  CAS  PubMed  Google Scholar 

  12. Wang T-Y, Forsythe JS, Nisbet DR, Parish CL. Promoting engraftment of transplanted neural stem cells/progenitors using biofunctionalised electrospun scaffolds. Biomaterials. 2012;33:9188–97.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang J et al. Physically associated synthetic hydrogels with long-term covalent stabilization for cell culture and stem cell transplantation. Adv Mater. 2011;23:5098–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. He L et al. Surface modification of PLLA nano-scaffolds with laminin multilayer by LbL assembly for enhancing neurite outgrowth. Macromol Biosci. 2013;13:1601–9.

    Article  CAS  PubMed  Google Scholar 

  15. Mahairaki V et al. Nanofiber matrices promote the neuronal differentiation of human embryonic stem cell-derived neural precursors in vitro. Tissue Eng Part A. 2011;17:855–63.

    Article  CAS  PubMed  Google Scholar 

  16. Lévesque SG, Shoichet MS. Synthesis of cell-adhesive dextran hydrogels and macroporous scaffolds. Biomaterials. 2006;27:5277–85.

    Article  PubMed  Google Scholar 

  17. Flanagan LA, Rebaza LM, Derzic S, Schwartz PH, Monuki ES. Regulation of human neural precursor cells by laminin and integrins. J Neurosci Res. 2006;83:845–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nakaji-Hirabayashi T, Kato K, Iwata H. Improvement of neural stem cell survival in collagen hydrogels by incorporating laminin-derived cell adhesive polypeptides. Bioconjug Chem. 2012;23:212–21.

    Article  CAS  PubMed  Google Scholar 

  19. He L et al. Synergistic effects of electrospun PLLA fiber dimension and pattern on neonatal mouse cerebellum C17.2 stem cells. Acta Biomater. 2010;6:2960–9.

    Article  CAS  PubMed  Google Scholar 

  20. Lim SH, Liu XY, Song H, Yarema KJ, Mao H-Q. The effect of nanofiber-guided cell alignment on the preferential differentiation of neural stem cells. Biomaterials. 2010;31:9031–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Christopherson GT, Song H, Mao H-Q. The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. Biomaterials. 2009;30:556–64.

    Article  CAS  PubMed  Google Scholar 

  22. Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani M-H, Ramakrishna S. Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials. 2008;29:4532–9.

    Article  CAS  PubMed  Google Scholar 

  23. Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials. 2005;26:2603–10.

    Article  CAS  PubMed  Google Scholar 

  24. Teng YD et al. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A. 2002;99:3024–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wong DY, Krebsbach PH, Hollister SJ. Brain cortex regeneration affected by scaffold architectures. J Neurosurg. 2008;109:715–22.

    Article  PubMed  Google Scholar 

  26. Cui Y, Xu Q, Chow PK-H, Wang D, Wang C-H. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials. 2013;34:8511–20.

    Article  CAS  PubMed  Google Scholar 

  27. Mishra V et al. Targeted brain delivery of AZT via transferrin anchored pegylated albumin nanoparticles. J Drug Target. 2006;14:45–53.

    Article  CAS  PubMed  Google Scholar 

  28. Karatas H et al. A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection. J Neurosci. 2009;29:13761–9.

    Article  CAS  PubMed  Google Scholar 

  29. 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. 2008;29:1509–17.

    Article  CAS  PubMed  Google Scholar 

  30. Ke W et al. Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials. 2009;30:6976–85.

    Article  CAS  PubMed  Google Scholar 

  31. Costantino L et al. Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier. J Control Release. 2005;108:84–96.

    Article  CAS  PubMed  Google Scholar 

  32. Tamargo RJ et al. Interstitial chemotherapy of the 9L gliosarcoma: controlled release polymers for drug delivery in the brain. Cancer Res. 1993;53:329–33.

    CAS  PubMed  Google Scholar 

  33. Emerich DF et al. Injectable VEGF hydrogels produce near complete neurological and anatomical protection following cerebral ischemia in rats. Cell Transplant. 2010;19:1063–71.

    Article  PubMed  Google Scholar 

  34. Nakaguchi K et al. Growth factors released from gelatin hydrogel microspheres increase new neurons in the adult mouse brain. Stem Cells Int. 2012;2012:915160.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Taylor SJ, Sakiyama-Elbert SE. Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model. J Control Release. 2006;116:204–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gupta D, Tator CH, Shoichet MS. Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials. 2006;27:2370–9.

    Article  CAS  PubMed  Google Scholar 

  37. Kang CE, Poon PC, Tator CH, Shoichet MS. A new paradigm for local and sustained release of therapeutic molecules to the injured spinal cord for neuroprotection and tissue repair. Tissue Eng Part A. 2009;15:595–604.

    Article  CAS  PubMed  Google Scholar 

  38. Cooke MJ, Wang Y, Morshead CM, Shoichet MS. Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain. Biomaterials. 2011;32:5688–97.

    Article  CAS  PubMed  Google Scholar 

  39. Wang Y, Cooke MJ, Morshead CM, Shoichet MS. Hydrogel delivery of erythropoietin to the brain for endogenous stem cell stimulation after stroke injury. Biomaterials. 2012;33:2681–92.

    Article  CAS  PubMed  Google Scholar 

  40. Hu X et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43:3063–70.

    Article  CAS  PubMed  Google Scholar 

  41. Kumar A, Alvarez-Croda D-M, Stoica BA, Faden AI, Loane DJ. Microglial/macrophage polarization dynamics following traumatic brain injury. J Neurotrauma. 2015. doi:10.1089/neu.2015.4268.

    PubMed  Google Scholar 

  42. Kigerl KA et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009;29:13435–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rapalino O et al. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 1998;4:814–21.

    Article  CAS  PubMed  Google Scholar 

  44. Shechter R et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med. 2009;6:e1000113.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Fridlender ZG et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: ‘N1’ versus ‘N2’ TAN. Cancer Cell. 2009;16:183–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kurimoto T et al. Neutrophils express oncomodulin and promote optic nerve regeneration. J Neurosci. 2013;33:14816–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol. 2007;28:138–45.

    Article  CAS  PubMed  Google Scholar 

  48. Mokarram N, Merchant A, Mukhatyar V, Patel G, Bellamkonda RV. Effect of modulating macrophage phenotype on peripheral nerve repair. Biomaterials. 2012;33:8793–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Spiller KL et al. Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials. 2015;37:194–207.

    Article  CAS  PubMed  Google Scholar 

  50. Boehler RM et al. Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype. Biotechnol Bioeng. 2014;111:1210–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. McBane JE, Matheson LA, Sharifpoor S, Santerre JP, Labow RS. Effect of polyurethane chemistry and protein coating on monocyte differentiation towards a wound healing phenotype macrophage. Biomaterials. 2009;30:5497–504.

    Article  CAS  PubMed  Google Scholar 

  52. Luu TU, Gott SC, Woo BWK, Rao MP, Liu WF. Micro- and nanopatterned topographical cues for regulating macrophage cell shape and phenotype. ACS Appl Mater Interfaces. 2015. doi:10.1021/acsami.5b10589.

    PubMed Central  Google Scholar 

  53. Garg K, Pullen NA, Oskeritzian CA, Ryan JJ, Bowlin GL. Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials. 2013;34:4439–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Almeida CR et al. Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte/macrophage responses: unraveling the effect of 3-D structures on inflammation. Acta Biomater. 2014;10:613–22.

    Article  CAS  PubMed  Google Scholar 

  55. Macaya DJ, Hayakawa K, Arai K, Spector M. Astrocyte infiltration into injectable collagen-based hydrogels containing FGF-2 to treat spinal cord injury. Biomaterials. 2013;34:3591–602.

    Article  CAS  PubMed  Google Scholar 

  56. Huang KF, Hsu WC, Chiu WT, Wang JY. Functional improvement and neurogenesis after collagen-GAG matrix implantation into surgical brain trauma. Biomaterials. 2012;33:2067–75.

    Article  CAS  PubMed  Google Scholar 

  57. Ernst B, Magnani JL. From carbohydrate leads to glycomimetic drugs. Nat Rev Drug Discov. 2009;8:661–77.

    Article  CAS  PubMed  Google Scholar 

  58. Huang ML, Smith RAA, Trieger GW, Godula K. Glycocalyx remodeling with proteoglycan mimetics promotes neural specification in embryonic stem cells. J Am Chem Soc. 2014;136:10565–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Liu P et al. Tailored chondroitin sulfate glycomimetics via a tunable multivalent scaffold for potentiating NGF/TrkA-induced neurogenesis. Chem Sci. 2015;6:450–6.

    Article  CAS  Google Scholar 

  60. Karumbaiah L et al. Chondroitin sulfate glycosaminoglycan hydrogels create endogenous niches for neural stem cells. Bioconjug Chem. 2015;26:2336–49.

    Article  CAS  PubMed  Google Scholar 

  61. Bencherif SA et al. Injectable preformed scaffolds with shape-memory properties. Proc Natl Acad Sci U S A. 2012;109:19590–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Koshy ST, Ferrante TC, Lewin SA, Mooney DJ. Injectable, porous, and cell-responsive gelatin cryogels. Biomaterials. 2014;35:2477–87.

    Article  CAS  PubMed  Google Scholar 

  63. Bencherif SA et al. Injectable cryogel-based whole-cell cancer vaccines. Nat Commun. 2015;6:7556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kim J et al. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat Biotechnol. 2015;33:64–72.

    Article  CAS  PubMed  Google Scholar 

  65. Sztriha LK et al. Monitoring brain repair in stroke using advanced magnetic resonance imaging. Stroke. 2012;43:3124–31.

    Article  PubMed  Google Scholar 

  66. Yang X et al. Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging. Carbohydr Polym. 2014;110:95–9.

    Article  CAS  PubMed  Google Scholar 

  67. Kim J. Il, Kim, B., Chun, C., Lee, S. H. & Song, S.-C. MRI-monitored long-term therapeutic hydrogel system for brain tumors without surgical resection. Biomaterials. 2012;33:4836–42.

    Article  CAS  PubMed  Google Scholar 

  68. Zhang Y et al. Injectable in situ forming hybrid iron oxide-hyaluronic acid hydrogel for magnetic resonance imaging and drug delivery. Macromol Biosci. 2014;14:1249–59.

    Article  CAS  PubMed  Google Scholar 

  69. Chan KWY et al. MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability. Nat Mater. 2013;12:268–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liang Y et al. Label-free imaging of gelatin-containing hydrogel scaffolds. Biomaterials. 2015;42:144–50.

    Article  CAS  PubMed  Google Scholar 

  71. Dorsey SM et al. Visualization of injectable hydrogels using chemical exchange saturation transfer MRI. ACS Biomater Sci Eng. 2015;1:227–37.

    Article  CAS  Google Scholar 

  72. Richardson TP, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nat Biotechnol. 2001;19:1029–34.

    Article  CAS  PubMed  Google Scholar 

  73. Vulic K, Shoichet MS. Tunable growth factor delivery from injectable hydrogels for tissue engineering. J Am Chem Soc. 2012;134:882–5.

    Article  CAS  PubMed  Google Scholar 

  74. Lin C-C, Metters AT. Bifunctional monolithic affinity hydrogels for dual-protein delivery. Biomacromolecules. 2008;9:789–95.

    Article  CAS  PubMed  Google Scholar 

  75. Shah RN et al. Supramolecular design of self-assembling nanofibers for cartilage regeneration. Proc Natl Acad Sci U S A. 2010;107:3293–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lim TC et al. Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1 release and compatible structural support. FASEB J. 2013;27:1023–33.

    Article  CAS  PubMed  Google Scholar 

  77. Santos T et al. Polymeric nanoparticles to control the differentiation of neural stem cells in the subventricular zone of the brain. ACS Nano. 2012;6:10463–74.

    Article  CAS  PubMed  Google Scholar 

  78. Conway A et al. Multivalent ligands control stem cell behaviour in vitro and in vivo. Nat Nanotechnol. 2013;8:831–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polym(Basel). 2011;3:1377–97.

    CAS  Google Scholar 

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Correspondence to Teck Chuan Lim.

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Lim, T.C., Spector, M. Biomaterials for Enhancing CNS Repair. Transl. Stroke Res. 8, 57–64 (2017). https://doi.org/10.1007/s12975-016-0470-x

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