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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

Co-culturing meningeal fibroblasts along with astrocytes in vitro can cause astrocyte reactivity and increased GFAP expression similar to in vivo glial scarring [157]. (A) Astrocytes (A-ctrl) in 2-D culture show perinuclear GFAP reactivity and are flat, round, or oval-shaped cells. (B) Long-term astrocyte–fibroblast co-cultures (A + F) show spindle-shaped astrocytes with elongated processes surrounded by meningeal fibroblasts. Also observed are astrocytic processes entering fibroblast territory (arrows) and brighter GFAP staining of astrocytes contacting fibroblasts. (C) Shows a 2-day mixed culture of astrocytes and fibroblasts showing strongly GFAP+ astrocytes (arrows) on and around patches of fibroblasts. (D) Shows differentiated astrocytes on collagen-coated silastic membranes without the presence of fibronectin+ cells. (E) Shows astrocyte–fibroblast co-culture 3 days following fibroblast addition and 24 h stretching (A + F-str) show disruption of processes, with clusters of star shaped astrocytes forming “bridges” of bundled processes across spaces shown as asterisks. Increased GFAP signals are found accumulated in stellate processes that are fibronectin+ (yellow). Fibronectin-positive fibroblasts (asterisks) remain evenly distributed after stretching. Bar = 20 μm. In (A–E), GFAP: green; fibronectin: red; nuclei: blue). Reprinted from Wanner et al. (2008). Copyright 2008 Wiley-Liss Inc. Reproduced with permission.
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Figure 10: Co-culturing meningeal fibroblasts along with astrocytes in vitro can cause astrocyte reactivity and increased GFAP expression similar to in vivo glial scarring [157]. (A) Astrocytes (A-ctrl) in 2-D culture show perinuclear GFAP reactivity and are flat, round, or oval-shaped cells. (B) Long-term astrocyte–fibroblast co-cultures (A + F) show spindle-shaped astrocytes with elongated processes surrounded by meningeal fibroblasts. Also observed are astrocytic processes entering fibroblast territory (arrows) and brighter GFAP staining of astrocytes contacting fibroblasts. (C) Shows a 2-day mixed culture of astrocytes and fibroblasts showing strongly GFAP+ astrocytes (arrows) on and around patches of fibroblasts. (D) Shows differentiated astrocytes on collagen-coated silastic membranes without the presence of fibronectin+ cells. (E) Shows astrocyte–fibroblast co-culture 3 days following fibroblast addition and 24 h stretching (A + F-str) show disruption of processes, with clusters of star shaped astrocytes forming “bridges” of bundled processes across spaces shown as asterisks. Increased GFAP signals are found accumulated in stellate processes that are fibronectin+ (yellow). Fibronectin-positive fibroblasts (asterisks) remain evenly distributed after stretching. Bar = 20 μm. In (A–E), GFAP: green; fibronectin: red; nuclei: blue). Reprinted from Wanner et al. (2008). Copyright 2008 Wiley-Liss Inc. Reproduced with permission.

Mentions: Second, Wanner et al. (2008) developed a model of mechanical injury to investigate the roles of astrocyte activation and meningeal fibroblasts in neuronal response (Figure 10). Newborn rat astrocytes with and without meningeal fibroblasts were grown on deformable silastic membrane and were exposed to two short pulses of stretch to mimic mechanical injury. Neurons derived from the cortex, spinal cord and dorsal root ganglia of postnatal and embryonic rat were seeded on the astrocyte cultures. The investigators found that stretch injury activated the astrocytes, resulting in significantly reduced neurite outgrowth compared to unstretched cultures. Interestingly, the extents of neurite outgrowth varied with age (greater inhibition in postnatal vs embryonic neurons) and type of neuronal population. This model highlights the importance of considering cell type and age when designing in vitro and animal model systems. For example, cell activation and the extent of glial scar formation is greatly enhanced in adult compared to neonatal animals, but unfortunately, few studies have focused on the heterogeneity of cell response to injury as a function of cell source or age (Ridet et al., 1997).


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

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

Co-culturing meningeal fibroblasts along with astrocytes in vitro can cause astrocyte reactivity and increased GFAP expression similar to in vivo glial scarring [157]. (A) Astrocytes (A-ctrl) in 2-D culture show perinuclear GFAP reactivity and are flat, round, or oval-shaped cells. (B) Long-term astrocyte–fibroblast co-cultures (A + F) show spindle-shaped astrocytes with elongated processes surrounded by meningeal fibroblasts. Also observed are astrocytic processes entering fibroblast territory (arrows) and brighter GFAP staining of astrocytes contacting fibroblasts. (C) Shows a 2-day mixed culture of astrocytes and fibroblasts showing strongly GFAP+ astrocytes (arrows) on and around patches of fibroblasts. (D) Shows differentiated astrocytes on collagen-coated silastic membranes without the presence of fibronectin+ cells. (E) Shows astrocyte–fibroblast co-culture 3 days following fibroblast addition and 24 h stretching (A + F-str) show disruption of processes, with clusters of star shaped astrocytes forming “bridges” of bundled processes across spaces shown as asterisks. Increased GFAP signals are found accumulated in stellate processes that are fibronectin+ (yellow). Fibronectin-positive fibroblasts (asterisks) remain evenly distributed after stretching. Bar = 20 μm. In (A–E), GFAP: green; fibronectin: red; nuclei: blue). Reprinted from Wanner et al. (2008). Copyright 2008 Wiley-Liss Inc. Reproduced with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 10: Co-culturing meningeal fibroblasts along with astrocytes in vitro can cause astrocyte reactivity and increased GFAP expression similar to in vivo glial scarring [157]. (A) Astrocytes (A-ctrl) in 2-D culture show perinuclear GFAP reactivity and are flat, round, or oval-shaped cells. (B) Long-term astrocyte–fibroblast co-cultures (A + F) show spindle-shaped astrocytes with elongated processes surrounded by meningeal fibroblasts. Also observed are astrocytic processes entering fibroblast territory (arrows) and brighter GFAP staining of astrocytes contacting fibroblasts. (C) Shows a 2-day mixed culture of astrocytes and fibroblasts showing strongly GFAP+ astrocytes (arrows) on and around patches of fibroblasts. (D) Shows differentiated astrocytes on collagen-coated silastic membranes without the presence of fibronectin+ cells. (E) Shows astrocyte–fibroblast co-culture 3 days following fibroblast addition and 24 h stretching (A + F-str) show disruption of processes, with clusters of star shaped astrocytes forming “bridges” of bundled processes across spaces shown as asterisks. Increased GFAP signals are found accumulated in stellate processes that are fibronectin+ (yellow). Fibronectin-positive fibroblasts (asterisks) remain evenly distributed after stretching. Bar = 20 μm. In (A–E), GFAP: green; fibronectin: red; nuclei: blue). Reprinted from Wanner et al. (2008). Copyright 2008 Wiley-Liss Inc. Reproduced with permission.
Mentions: Second, Wanner et al. (2008) developed a model of mechanical injury to investigate the roles of astrocyte activation and meningeal fibroblasts in neuronal response (Figure 10). Newborn rat astrocytes with and without meningeal fibroblasts were grown on deformable silastic membrane and were exposed to two short pulses of stretch to mimic mechanical injury. Neurons derived from the cortex, spinal cord and dorsal root ganglia of postnatal and embryonic rat were seeded on the astrocyte cultures. The investigators found that stretch injury activated the astrocytes, resulting in significantly reduced neurite outgrowth compared to unstretched cultures. Interestingly, the extents of neurite outgrowth varied with age (greater inhibition in postnatal vs embryonic neurons) and type of neuronal population. This model highlights the importance of considering cell type and age when designing in vitro and animal model systems. For example, cell activation and the extent of glial scar formation is greatly enhanced in adult compared to neonatal animals, but unfortunately, few studies have focused on the heterogeneity of cell response to injury as a function of cell source or age (Ridet et al., 1997).

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