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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

Regeneration of the optic nerve in mice using an EGFR blocking molecule, PD168393. Optic nerves stained with antibodies against GAP43 compared to controls (A,C) or PD168393-treated (B,D) mice. Lectin staining and visual inspection were used to identify the injury site (marked by C). The images in (C,D) are magnified views of the post crush area that were treated and untreated by PD168393. In (C), the control nerve shows very few GAP-43 fibers whereas in (D), numerous regenerating fibers are observed, including some that had changed their direction (filled triangle). Scale bar = 100 μm in (A,B) and 50 μm in (C,D). Reprinted from Koprivica et al. (2005). Copyright Science AAAS 2005. Reproduced with permission.
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Figure 11: Regeneration of the optic nerve in mice using an EGFR blocking molecule, PD168393. Optic nerves stained with antibodies against GAP43 compared to controls (A,C) or PD168393-treated (B,D) mice. Lectin staining and visual inspection were used to identify the injury site (marked by C). The images in (C,D) are magnified views of the post crush area that were treated and untreated by PD168393. In (C), the control nerve shows very few GAP-43 fibers whereas in (D), numerous regenerating fibers are observed, including some that had changed their direction (filled triangle). Scale bar = 100 μm in (A,B) and 50 μm in (C,D). Reprinted from Koprivica et al. (2005). Copyright Science AAAS 2005. Reproduced with permission.

Mentions: Fortunately, entry into the cell cycle and drug candidates that may control this response are heavily investigated in the cancer biology field, as uncontrolled proliferation is a hallmark of cancer cells. In fact, a recent study (Koprivica et al., 2005) was undertaken to screen at least 400 small molecules for their ability to promote neurite outgrowth on an inhibitory surface of myelin (a component of spinal cord injury scar); the majority of compounds had no effect, but several drugs related to inhibiting the epidermal growth factor receptor (EGFR) were able to block the inhibitory effect of the myelin substrate and resulted in robust neurite outgrowth, as shown in Figure 11. These effects were corroborated in a mouse model of optic nerve injury, resulting in significant nerve regeneration in treated animals compared to control mice without treatment. The cellular mechanism behind the effectiveness of EGFR inhibition relates to intracellular signaling cascades involving known players in cancer biology, including the MAPK, Akt and JNK pathways that impact DNA synthesis and cell proliferation (Oda et al., 2005). Interestingly, EGFR is not the only mediator of these pathways that has been linked to CNS injury (Di Giovanni et al., 2005; Milenkovic et al., 2005; Neary and Kang, 2005; Nicole et al., 2005; Kaneko et al., 2007; Lim et al., 2007) and several molecules that inhibit these pathways are already approved as potential drugs for cancer treatment. Thus, a promising and immediately feasible line of research is to test these drugs in conjunction with neuroprosthetic devices to promote neuronal survival and inhibit scar formation and inflammation. This approach is particularly exciting because of the immediate implications for treatment of CNS injury (Miller, 2005) and like the possible insights gleaned from developmental biology mentioned above, the wealth of knowledge from cancer biology provides potentially powerful new avenues of exploration for addressing CNS injuries including those associated with neuroprosthetic devices.


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

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

Regeneration of the optic nerve in mice using an EGFR blocking molecule, PD168393. Optic nerves stained with antibodies against GAP43 compared to controls (A,C) or PD168393-treated (B,D) mice. Lectin staining and visual inspection were used to identify the injury site (marked by C). The images in (C,D) are magnified views of the post crush area that were treated and untreated by PD168393. In (C), the control nerve shows very few GAP-43 fibers whereas in (D), numerous regenerating fibers are observed, including some that had changed their direction (filled triangle). Scale bar = 100 μm in (A,B) and 50 μm in (C,D). Reprinted from Koprivica et al. (2005). Copyright Science AAAS 2005. Reproduced with permission.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 11: Regeneration of the optic nerve in mice using an EGFR blocking molecule, PD168393. Optic nerves stained with antibodies against GAP43 compared to controls (A,C) or PD168393-treated (B,D) mice. Lectin staining and visual inspection were used to identify the injury site (marked by C). The images in (C,D) are magnified views of the post crush area that were treated and untreated by PD168393. In (C), the control nerve shows very few GAP-43 fibers whereas in (D), numerous regenerating fibers are observed, including some that had changed their direction (filled triangle). Scale bar = 100 μm in (A,B) and 50 μm in (C,D). Reprinted from Koprivica et al. (2005). Copyright Science AAAS 2005. Reproduced with permission.
Mentions: Fortunately, entry into the cell cycle and drug candidates that may control this response are heavily investigated in the cancer biology field, as uncontrolled proliferation is a hallmark of cancer cells. In fact, a recent study (Koprivica et al., 2005) was undertaken to screen at least 400 small molecules for their ability to promote neurite outgrowth on an inhibitory surface of myelin (a component of spinal cord injury scar); the majority of compounds had no effect, but several drugs related to inhibiting the epidermal growth factor receptor (EGFR) were able to block the inhibitory effect of the myelin substrate and resulted in robust neurite outgrowth, as shown in Figure 11. These effects were corroborated in a mouse model of optic nerve injury, resulting in significant nerve regeneration in treated animals compared to control mice without treatment. The cellular mechanism behind the effectiveness of EGFR inhibition relates to intracellular signaling cascades involving known players in cancer biology, including the MAPK, Akt and JNK pathways that impact DNA synthesis and cell proliferation (Oda et al., 2005). Interestingly, EGFR is not the only mediator of these pathways that has been linked to CNS injury (Di Giovanni et al., 2005; Milenkovic et al., 2005; Neary and Kang, 2005; Nicole et al., 2005; Kaneko et al., 2007; Lim et al., 2007) and several molecules that inhibit these pathways are already approved as potential drugs for cancer treatment. Thus, a promising and immediately feasible line of research is to test these drugs in conjunction with neuroprosthetic devices to promote neuronal survival and inhibit scar formation and inflammation. This approach is particularly exciting because of the immediate implications for treatment of CNS injury (Miller, 2005) and like the possible insights gleaned from developmental biology mentioned above, the wealth of knowledge from cancer biology provides potentially powerful new avenues of exploration for addressing CNS injuries including those associated with neuroprosthetic devices.

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