Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces

Christopher L. Klaver, Michael Caplan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Implantation of deep-brain recording devices, to restore lost functionality, is a traumatic event which inevitably elicits reactive gliosis. Gliosis involves the proliferation, hypertrophy, and process extension of astrocytes in the vicinity of the trauma. The resulting physical component of reactive gliosis involves the development of a glial scar composed primarily of reactive astrocytes and the extracellular matrix products they produce. As a result of glial scar formation, the ability to transmit signals to or from the target neuron is lost due to scar tissue increasing the distance of the neuron from the implant. Surface modifications capable of decreasing scar tissue formation should result in improved long-term implantneuron communication. Surface modifications influencing astrocyte proliferation represent a method of mitigating glial scar development. Potentially, the severity of glial scar formation could be minimized, for example, by limiting the number of astrocytes actively participating in reactive gliosis. Transforming growth factor-beta one (TGF-β1) has been shown to decrease the rate of astrocyte proliferation. Covalent bonding of the cytokine to dextran surfaces maintains the efficacy of TGF-β1 toward astrocyte proliferation over the long-term since the growth factor cannot diffuse away or become internalized by the astrocytes. Astrocyte culture proliferation was measured via colorimetric assays against in solution concentrations of TGF-β1 for determining the optimum concentration of TGF-β1 for proliferation inhibition. This experiment demonstrated a 44.9%±32.6% (p < 0.0003) decrease in proliferation at 10 ng/mL TGF-β1. 7 A predictive receptor-ligand model based on mass action kinetics was developed to equate three-dimensional (in solution) TGF-β1 concentrations to two-dimensional (surface bound) TGF-β1 concentrations. TGF-β1 was bound to immobilized dextran surfaces. Poly-L-lysine coated surfaces were treated with oxidized dextran. The dextran was re-oxidized with sodium metaperiodate to generate aldehyde binding site locations to which TGF-β1 was covalently bound via a Michael addition reaction. The resulting surfaces inhibited in vitro proliferation by 53.8% ± 25.2% (p < 0.0003). These results demonstrate that covalently bound TGF-β1 retains its ability to inhibit astrocyte proliferation.

Original languageEnglish (US)
Title of host publicationAIChE Annual Meeting, Conference Proceedings
Pages5087
Number of pages1
StatePublished - 2005
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States
Duration: Oct 30 2005Nov 4 2005

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
CountryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

Fingerprint

Modulation
Dextran
Neurons
Surface treatment
Tissue
Astrocytes
Intercellular Signaling Peptides and Proteins
Addition reactions
Binding sites
Aldehydes
Assays
Brain
Ligands
Sodium
Kinetics
Neuroglia
Communication
Experiments

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Klaver, C. L., & Caplan, M. (2005). Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces. In AIChE Annual Meeting, Conference Proceedings (pp. 5087)

Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces. / Klaver, Christopher L.; Caplan, Michael.

AIChE Annual Meeting, Conference Proceedings. 2005. p. 5087.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Klaver, CL & Caplan, M 2005, Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces. in AIChE Annual Meeting, Conference Proceedings. pp. 5087, 05AIChE: 2005 AIChE Annual Meeting and Fall Showcase, Cincinnati, OH, United States, 10/30/05.
Klaver CL, Caplan M. Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces. In AIChE Annual Meeting, Conference Proceedings. 2005. p. 5087
Klaver, Christopher L. ; Caplan, Michael. / Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces. AIChE Annual Meeting, Conference Proceedings. 2005. pp. 5087
@inproceedings{6b3ca9933a434850a8321ec135c28e35,
title = "Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces",
abstract = "Implantation of deep-brain recording devices, to restore lost functionality, is a traumatic event which inevitably elicits reactive gliosis. Gliosis involves the proliferation, hypertrophy, and process extension of astrocytes in the vicinity of the trauma. The resulting physical component of reactive gliosis involves the development of a glial scar composed primarily of reactive astrocytes and the extracellular matrix products they produce. As a result of glial scar formation, the ability to transmit signals to or from the target neuron is lost due to scar tissue increasing the distance of the neuron from the implant. Surface modifications capable of decreasing scar tissue formation should result in improved long-term implantneuron communication. Surface modifications influencing astrocyte proliferation represent a method of mitigating glial scar development. Potentially, the severity of glial scar formation could be minimized, for example, by limiting the number of astrocytes actively participating in reactive gliosis. Transforming growth factor-beta one (TGF-β1) has been shown to decrease the rate of astrocyte proliferation. Covalent bonding of the cytokine to dextran surfaces maintains the efficacy of TGF-β1 toward astrocyte proliferation over the long-term since the growth factor cannot diffuse away or become internalized by the astrocytes. Astrocyte culture proliferation was measured via colorimetric assays against in solution concentrations of TGF-β1 for determining the optimum concentration of TGF-β1 for proliferation inhibition. This experiment demonstrated a 44.9{\%}±32.6{\%} (p < 0.0003) decrease in proliferation at 10 ng/mL TGF-β1. 7 A predictive receptor-ligand model based on mass action kinetics was developed to equate three-dimensional (in solution) TGF-β1 concentrations to two-dimensional (surface bound) TGF-β1 concentrations. TGF-β1 was bound to immobilized dextran surfaces. Poly-L-lysine coated surfaces were treated with oxidized dextran. The dextran was re-oxidized with sodium metaperiodate to generate aldehyde binding site locations to which TGF-β1 was covalently bound via a Michael addition reaction. The resulting surfaces inhibited in vitro proliferation by 53.8{\%} ± 25.2{\%} (p < 0.0003). These results demonstrate that covalently bound TGF-β1 retains its ability to inhibit astrocyte proliferation.",
author = "Klaver, {Christopher L.} and Michael Caplan",
year = "2005",
language = "English (US)",
pages = "5087",
booktitle = "AIChE Annual Meeting, Conference Proceedings",

}

TY - GEN

T1 - Modulation of astrocyte behavior via transforming growth factor & beta-1 conjugated surfaces

AU - Klaver, Christopher L.

AU - Caplan, Michael

PY - 2005

Y1 - 2005

N2 - Implantation of deep-brain recording devices, to restore lost functionality, is a traumatic event which inevitably elicits reactive gliosis. Gliosis involves the proliferation, hypertrophy, and process extension of astrocytes in the vicinity of the trauma. The resulting physical component of reactive gliosis involves the development of a glial scar composed primarily of reactive astrocytes and the extracellular matrix products they produce. As a result of glial scar formation, the ability to transmit signals to or from the target neuron is lost due to scar tissue increasing the distance of the neuron from the implant. Surface modifications capable of decreasing scar tissue formation should result in improved long-term implantneuron communication. Surface modifications influencing astrocyte proliferation represent a method of mitigating glial scar development. Potentially, the severity of glial scar formation could be minimized, for example, by limiting the number of astrocytes actively participating in reactive gliosis. Transforming growth factor-beta one (TGF-β1) has been shown to decrease the rate of astrocyte proliferation. Covalent bonding of the cytokine to dextran surfaces maintains the efficacy of TGF-β1 toward astrocyte proliferation over the long-term since the growth factor cannot diffuse away or become internalized by the astrocytes. Astrocyte culture proliferation was measured via colorimetric assays against in solution concentrations of TGF-β1 for determining the optimum concentration of TGF-β1 for proliferation inhibition. This experiment demonstrated a 44.9%±32.6% (p < 0.0003) decrease in proliferation at 10 ng/mL TGF-β1. 7 A predictive receptor-ligand model based on mass action kinetics was developed to equate three-dimensional (in solution) TGF-β1 concentrations to two-dimensional (surface bound) TGF-β1 concentrations. TGF-β1 was bound to immobilized dextran surfaces. Poly-L-lysine coated surfaces were treated with oxidized dextran. The dextran was re-oxidized with sodium metaperiodate to generate aldehyde binding site locations to which TGF-β1 was covalently bound via a Michael addition reaction. The resulting surfaces inhibited in vitro proliferation by 53.8% ± 25.2% (p < 0.0003). These results demonstrate that covalently bound TGF-β1 retains its ability to inhibit astrocyte proliferation.

AB - Implantation of deep-brain recording devices, to restore lost functionality, is a traumatic event which inevitably elicits reactive gliosis. Gliosis involves the proliferation, hypertrophy, and process extension of astrocytes in the vicinity of the trauma. The resulting physical component of reactive gliosis involves the development of a glial scar composed primarily of reactive astrocytes and the extracellular matrix products they produce. As a result of glial scar formation, the ability to transmit signals to or from the target neuron is lost due to scar tissue increasing the distance of the neuron from the implant. Surface modifications capable of decreasing scar tissue formation should result in improved long-term implantneuron communication. Surface modifications influencing astrocyte proliferation represent a method of mitigating glial scar development. Potentially, the severity of glial scar formation could be minimized, for example, by limiting the number of astrocytes actively participating in reactive gliosis. Transforming growth factor-beta one (TGF-β1) has been shown to decrease the rate of astrocyte proliferation. Covalent bonding of the cytokine to dextran surfaces maintains the efficacy of TGF-β1 toward astrocyte proliferation over the long-term since the growth factor cannot diffuse away or become internalized by the astrocytes. Astrocyte culture proliferation was measured via colorimetric assays against in solution concentrations of TGF-β1 for determining the optimum concentration of TGF-β1 for proliferation inhibition. This experiment demonstrated a 44.9%±32.6% (p < 0.0003) decrease in proliferation at 10 ng/mL TGF-β1. 7 A predictive receptor-ligand model based on mass action kinetics was developed to equate three-dimensional (in solution) TGF-β1 concentrations to two-dimensional (surface bound) TGF-β1 concentrations. TGF-β1 was bound to immobilized dextran surfaces. Poly-L-lysine coated surfaces were treated with oxidized dextran. The dextran was re-oxidized with sodium metaperiodate to generate aldehyde binding site locations to which TGF-β1 was covalently bound via a Michael addition reaction. The resulting surfaces inhibited in vitro proliferation by 53.8% ± 25.2% (p < 0.0003). These results demonstrate that covalently bound TGF-β1 retains its ability to inhibit astrocyte proliferation.

UR - http://www.scopus.com/inward/record.url?scp=33645638977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645638977&partnerID=8YFLogxK

M3 - Conference contribution

SP - 5087

BT - AIChE Annual Meeting, Conference Proceedings

ER -