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Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology.

Leach JB, Achyuta AK, Murthy SK - Front Neuroeng (2010)

Bottom Line: Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke.Within the context of the device-nervous system interface and central nervous system implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell biology.Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biochemical Engineering, University of Maryland Baltimore, MD, USA.

ABSTRACT
Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

No MeSH data available.


Related in: MedlinePlus

GFAP reactivity of uncoated silicon microelectrodes (G, J) and an anti-inflammatory peptide (α-MSH) tethered electrode (H, K) following 1 week and 4 weeks of implantation in rats. The α-MSH coated electrodes elicited mitigated astrocytic and microglial reactivity (not shown here) indicating bioactivity of the coated implant. Scale Bar = 100 μm. Images reprinted from He et al. (2007). Copyright Wiley-VCH Verlag GmbH & Co. KGaA 2007. Reproduced with permission.
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Figure 7: GFAP reactivity of uncoated silicon microelectrodes (G, J) and an anti-inflammatory peptide (α-MSH) tethered electrode (H, K) following 1 week and 4 weeks of implantation in rats. The α-MSH coated electrodes elicited mitigated astrocytic and microglial reactivity (not shown here) indicating bioactivity of the coated implant. Scale Bar = 100 μm. Images reprinted from He et al. (2007). Copyright Wiley-VCH Verlag GmbH & Co. KGaA 2007. Reproduced with permission.

Mentions: Future-generation neural prosthetic devices are being designed with a greater emphasis on reducing the tissue encapsulation problem to ensure consistent recordings in clinical settings. Some of the most promising work conducted in alleviating the glial scar problem has included bioactive coatings, reducing mechanical mismatch between the probe-brain interfaces and developing wireless implantable neuroelectrodes (see Table 2). For instance, Webb et al. (2001) immobilized a neural cell adhesion molecule (L1-NCAM) on glass substrates and showed in vitro that these bioactive coatings attract primary CNS neurons and support neurite outgrowth while repelling primary astrocytes, meningeal cells and fibroblasts. However, one of the limitations of this work was that the study did not include microglia, the frontline responder cells, to completely validate their model. Another bioactive coating strategy was developed by He et al. (2007) with an immobilized anti-inflammatory tridecapeptide, α-MSH, on silicon probes, demonstrating diminished inflammation and gliosis (Figure 7). Although this study illustrated exceptionally promising results with respect to in vitro as well as in vivo substantiation of the bioactivity of the peptide tethered electrodes, the group did not evaluate or show results pertaining to neuronal loss around the electrodes, which has been a major impediment to obtaining chronic consistent recordings (Biran et al., 2005). Cell-based bioactive coatings on neural probes have also been examined; Schlosshauer et al. (2001) encapsulated rat Schwann cells within a fibrin gel and placed the gel in contact with a slice of rat spinal cord adhered to a neural probe. To simulate a glial scar, fibroblasts were pre-adhered onto the probe, which had sieves in the size range of 40–70 μm. With this arrangement, the authors observed marked neurite penetration of the sieves relative to controls with no Schwann cells.


Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology.

Leach JB, Achyuta AK, Murthy SK - Front Neuroeng (2010)

GFAP reactivity of uncoated silicon microelectrodes (G, J) and an anti-inflammatory peptide (α-MSH) tethered electrode (H, K) following 1 week and 4 weeks of implantation in rats. The α-MSH coated electrodes elicited mitigated astrocytic and microglial reactivity (not shown here) indicating bioactivity of the coated implant. Scale Bar = 100 μm. Images reprinted from He et al. (2007). Copyright Wiley-VCH Verlag GmbH & Co. KGaA 2007. Reproduced with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821180&req=5

Figure 7: GFAP reactivity of uncoated silicon microelectrodes (G, J) and an anti-inflammatory peptide (α-MSH) tethered electrode (H, K) following 1 week and 4 weeks of implantation in rats. The α-MSH coated electrodes elicited mitigated astrocytic and microglial reactivity (not shown here) indicating bioactivity of the coated implant. Scale Bar = 100 μm. Images reprinted from He et al. (2007). Copyright Wiley-VCH Verlag GmbH & Co. KGaA 2007. Reproduced with permission.
Mentions: Future-generation neural prosthetic devices are being designed with a greater emphasis on reducing the tissue encapsulation problem to ensure consistent recordings in clinical settings. Some of the most promising work conducted in alleviating the glial scar problem has included bioactive coatings, reducing mechanical mismatch between the probe-brain interfaces and developing wireless implantable neuroelectrodes (see Table 2). For instance, Webb et al. (2001) immobilized a neural cell adhesion molecule (L1-NCAM) on glass substrates and showed in vitro that these bioactive coatings attract primary CNS neurons and support neurite outgrowth while repelling primary astrocytes, meningeal cells and fibroblasts. However, one of the limitations of this work was that the study did not include microglia, the frontline responder cells, to completely validate their model. Another bioactive coating strategy was developed by He et al. (2007) with an immobilized anti-inflammatory tridecapeptide, α-MSH, on silicon probes, demonstrating diminished inflammation and gliosis (Figure 7). Although this study illustrated exceptionally promising results with respect to in vitro as well as in vivo substantiation of the bioactivity of the peptide tethered electrodes, the group did not evaluate or show results pertaining to neuronal loss around the electrodes, which has been a major impediment to obtaining chronic consistent recordings (Biran et al., 2005). Cell-based bioactive coatings on neural probes have also been examined; Schlosshauer et al. (2001) encapsulated rat Schwann cells within a fibrin gel and placed the gel in contact with a slice of rat spinal cord adhered to a neural probe. To simulate a glial scar, fibroblasts were pre-adhered onto the probe, which had sieves in the size range of 40–70 μm. With this arrangement, the authors observed marked neurite penetration of the sieves relative to controls with no Schwann cells.

Bottom Line: Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke.Within the context of the device-nervous system interface and central nervous system implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell biology.Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biochemical Engineering, University of Maryland Baltimore, MD, USA.

ABSTRACT
Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

No MeSH data available.


Related in: MedlinePlus