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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

An in vitro model of glial scarring developed by Polikov and colleagues (Polikov et al. , 2006, 2009) using an optimized cell culture monolayer of primary astrocytes and microglia. (A) Upon implantation of a 50-μm metallic wire into this culture, distinct traits of glial scarring are observed, such as microglial (red) activation and attachment to the implanted microwires, astrocyte (green) activation beyond the microglial layer in the form of GFAP up-regulation and encapsulation of wires by reactive astrocytes. (B) Shows the scar phenomena at higher magnification. Reprinted from Polikov et al. (2006). Copyright 2006, with permission from Elsevier.
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Figure 9: An in vitro model of glial scarring developed by Polikov and colleagues (Polikov et al. , 2006, 2009) using an optimized cell culture monolayer of primary astrocytes and microglia. (A) Upon implantation of a 50-μm metallic wire into this culture, distinct traits of glial scarring are observed, such as microglial (red) activation and attachment to the implanted microwires, astrocyte (green) activation beyond the microglial layer in the form of GFAP up-regulation and encapsulation of wires by reactive astrocytes. (B) Shows the scar phenomena at higher magnification. Reprinted from Polikov et al. (2006). Copyright 2006, with permission from Elsevier.

Mentions: Of particular relevance to neuroprosthetic devices are studies carried out by three groups with the intent of developing in vitro co-culture models of neuronal response to glial scar resulting from microelectrode implantation and mechanical injury. First, studies by Polikov and Reichert adapted an established in vitro model of neuroinflammatory response toward the investigation of glial response to microelectrode implantation (Polikov et al., 2006, 2009) (Figure 9). This model system consists of a confluent layer of neurons, astrocytes and microglia that are derived from embryonic rat midbrain. An injury was induced to the culture by scraping away a section of the cells and/or placing a foreign body (50 μm diameter stainless steel wire) on top of the cells. The cultures were assessed at 6 h and 10 days after injury by immunocytochemical staining for markers for neurons and reactive forms of astrocytes and microglia. Their initial report found that the developed in vitro model compared favorably to in vivo response to injury in the brain (Polikov et al., 2006), whereas their follow-up report focused on improving the reproducibility of the model system via optimized culture conditions and established a quantitative method for interpreting the results (Polikov et al., 2009). Because this model system was carefully designed to account for multiple cell types and provides a mechanism to rigorously compare different types of injuries and implant materials, this approach has great potential for unveiling fundamental mechanisms of glial scar formation and neuroprosthetic performance.


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

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

An in vitro model of glial scarring developed by Polikov and colleagues (Polikov et al. , 2006, 2009) using an optimized cell culture monolayer of primary astrocytes and microglia. (A) Upon implantation of a 50-μm metallic wire into this culture, distinct traits of glial scarring are observed, such as microglial (red) activation and attachment to the implanted microwires, astrocyte (green) activation beyond the microglial layer in the form of GFAP up-regulation and encapsulation of wires by reactive astrocytes. (B) Shows the scar phenomena at higher magnification. Reprinted from Polikov et al. (2006). Copyright 2006, with permission from Elsevier.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: An in vitro model of glial scarring developed by Polikov and colleagues (Polikov et al. , 2006, 2009) using an optimized cell culture monolayer of primary astrocytes and microglia. (A) Upon implantation of a 50-μm metallic wire into this culture, distinct traits of glial scarring are observed, such as microglial (red) activation and attachment to the implanted microwires, astrocyte (green) activation beyond the microglial layer in the form of GFAP up-regulation and encapsulation of wires by reactive astrocytes. (B) Shows the scar phenomena at higher magnification. Reprinted from Polikov et al. (2006). Copyright 2006, with permission from Elsevier.
Mentions: Of particular relevance to neuroprosthetic devices are studies carried out by three groups with the intent of developing in vitro co-culture models of neuronal response to glial scar resulting from microelectrode implantation and mechanical injury. First, studies by Polikov and Reichert adapted an established in vitro model of neuroinflammatory response toward the investigation of glial response to microelectrode implantation (Polikov et al., 2006, 2009) (Figure 9). This model system consists of a confluent layer of neurons, astrocytes and microglia that are derived from embryonic rat midbrain. An injury was induced to the culture by scraping away a section of the cells and/or placing a foreign body (50 μm diameter stainless steel wire) on top of the cells. The cultures were assessed at 6 h and 10 days after injury by immunocytochemical staining for markers for neurons and reactive forms of astrocytes and microglia. Their initial report found that the developed in vitro model compared favorably to in vivo response to injury in the brain (Polikov et al., 2006), whereas their follow-up report focused on improving the reproducibility of the model system via optimized culture conditions and established a quantitative method for interpreting the results (Polikov et al., 2009). Because this model system was carefully designed to account for multiple cell types and provides a mechanism to rigorously compare different types of injuries and implant materials, this approach has great potential for unveiling fundamental mechanisms of glial scar formation and neuroprosthetic performance.

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