Hydrogels derived from central nervous system extracellular matrix

Christopher J. Medberry; Peter M. Crapo; Bernard F. Siu; Christopher A. Carruthers; Matthew T. Wolf; Shailesh P. Nagarkar; Vineet Agrawal; Kristen E. Jones; Jeremy Kelly; Scott A. Johnson; Sachin S. Velankar; Simon C. Watkins; Michel Modo; Stephen F. Badylak

doi:10.1016/j.biomaterials.2012.10.062

Hydrogels derived from central nervous system extracellular matrix

Christopher J. Medberry, Peter M. Crapo, Bernard F. Siu, Christopher A. Carruthers, Matthew T. Wolf, Shailesh P. Nagarkar, Vineet Agrawal, Kristen E. Jones, Jeremy Kelly, Scott A. Johnson, Sachin S. Velankar, Simon C. Watkins, Michel Modo, Stephen F. Badylak

Neurosurgery

Research output: Contribution to journal › Article › peer-review

235 Scopus citations

Abstract

Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair.

Original language	English (US)
Pages (from-to)	1033-1040
Number of pages	8
Journal	Biomaterials
Volume	34
Issue number	4
DOIs	https://doi.org/10.1016/j.biomaterials.2012.10.062
State	Published - Jan 2013

Bibliographical note

Funding Information:
Christopher Medberry was partially supported by the NIH-NHLBI training grant ( T32-EB001026 ) entitled “Cellular Approaches to Tissue Engineering and Regeneration.” Peter Crapo was partially supported by an Ocular Tissue Engineering and Regenerative Ophthalmology (OTERO) Fellowship from the Louis J. Fox Center for Vision Restoration (a joint program of UPMC and the University of Pittsburgh). Matthew Wolf was partially supported by the NIH-NHLBI training grant ( T32-HL76124-6 ) entitled “Cardiovascular Bioengineering Training Program.” Christopher Carruthers was partially supported by the National Science Foundation (NSF) Graduate Research Fellowship. Shailesh Nagarkar was partially supported by a grant from the National Science Foundation ( NSF-0932901 ). Vineet Agrawal was supported by a NIH F30 training grant ( 1F30-HL102990 (VA)). The authors would like to thank Deanna Rhoads, Gregory A. Gibson, the McGowan Histology Center for histologic section preparation, and Biologic Imaging at the University of Pittsburgh for access to imaging facilities.

Keywords

Central nervous system
ECM (extracellular matrix)
Hydrogel
Regenerative medicine
Scaffold
Tissue engineering

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title = "Hydrogels derived from central nervous system extracellular matrix",

abstract = "Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair.",

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author = "Medberry, {Christopher J.} and Crapo, {Peter M.} and Siu, {Bernard F.} and Carruthers, {Christopher A.} and Wolf, {Matthew T.} and Nagarkar, {Shailesh P.} and Vineet Agrawal and Jones, {Kristen E.} and Jeremy Kelly and Johnson, {Scott A.} and Velankar, {Sachin S.} and Watkins, {Simon C.} and Michel Modo and Badylak, {Stephen F.}",

note = "Funding Information: Christopher Medberry was partially supported by the NIH-NHLBI training grant ( T32-EB001026 ) entitled “Cellular Approaches to Tissue Engineering and Regeneration.” Peter Crapo was partially supported by an Ocular Tissue Engineering and Regenerative Ophthalmology (OTERO) Fellowship from the Louis J. Fox Center for Vision Restoration (a joint program of UPMC and the University of Pittsburgh). Matthew Wolf was partially supported by the NIH-NHLBI training grant ( T32-HL76124-6 ) entitled “Cardiovascular Bioengineering Training Program.” Christopher Carruthers was partially supported by the National Science Foundation (NSF) Graduate Research Fellowship. Shailesh Nagarkar was partially supported by a grant from the National Science Foundation ( NSF-0932901 ). Vineet Agrawal was supported by a NIH F30 training grant ( 1F30-HL102990 (VA)). The authors would like to thank Deanna Rhoads, Gregory A. Gibson, the McGowan Histology Center for histologic section preparation, and Biologic Imaging at the University of Pittsburgh for access to imaging facilities. ",

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AU - Jones, Kristen E.

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AU - Watkins, Simon C.

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AU - Badylak, Stephen F.

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Hydrogels derived from central nervous system extracellular matrix

Abstract

Bibliographical note

Keywords

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