Silk hydrogels as soft substrates for neural tissue engineering

Amy M. Hopkins, Laura De Laporte, Federico Tortelli, Elise Spedden, Cristian Staii, Timothy J. Atherton, Jeffrey A. Hubbell, David L. Kaplan

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

There is great need for soft biomaterials that match the stiffness of human tissues for tissue engineering and regeneration. Hydrogels are frequently employed for extracellular matrix functionalization and to provide appropriate mechanical cues. It is challenging, however, to achieve structural integrity and retain bioactive molecules in hydrogels for complex tissue formation that may take months to develop. This work aims to investigate mechanical and biochemical characteristics of silk hydrogels for soft tissue engineering, specifically for the nervous system. The stiffness of 1 to 8% silk hydrogels, measured by atomic force microscopy, is 4 to 33 kPa. The structural integrity of silk gels is maintained throughout embryonic chick dorsal root ganglion (cDRG) explant culture over 4 days whereas fibrin and collagen gels decrease in mass over time. Neurite extension of cDRGs cultured on 2 and 4% silk hydrogels exhibit greater growth than softer or stiffer gels. Silk hydrogels release <5% of neurotrophin-3 (NT-3) over 2 weeks and 11-day old gels show maintenance of growth factor bioactivity. Finally, fibronectin- and NT-3-functionalized silk gels elicit increased axonal bundling suggesting their use in bridging nerve injuries. These results support silk hydrogels as soft and sustainable biomaterials for neural tissue engineering. Silk hydrogels are soft biomaterials of stiffness matching that of nervous system tissues. Significant chick dorsal root ganglion explant outgrowth is exhibited on 2 to 4% w/v silk hydrogels supplemented with neurotrophic factors exemplifying their employment in extracellular matrix functionalization for neural tissue engineering applications.

Original languageEnglish
Pages (from-to)5140-5149
Number of pages10
JournalAdvanced Functional Materials
Volume23
Issue number41
DOIs
StatePublished - Nov 6 2013
Externally publishedYes

Fingerprint

silk
Hydrogels
Silk
tissue engineering
Tissue engineering
Substrates
Gels
gels
Biocompatible Materials
Biomaterials
Neurotrophin 3
nervous system
stiffness
Stiffness
Neurology
Structural integrity
Tissue
integrity
fibrin
Tissue regeneration

Keywords

  • biomedical applications
  • biomimetics
  • extracellular matrix engineering
  • hydrogels
  • tissue engineering

ASJC Scopus subject areas

  • Biomaterials
  • Electrochemistry
  • Condensed Matter Physics
  • Electronic, Optical and Magnetic Materials

Cite this

Hopkins, A. M., De Laporte, L., Tortelli, F., Spedden, E., Staii, C., Atherton, T. J., ... Kaplan, D. L. (2013). Silk hydrogels as soft substrates for neural tissue engineering. Advanced Functional Materials, 23(41), 5140-5149. https://doi.org/10.1002/adfm.201300435

Silk hydrogels as soft substrates for neural tissue engineering. / Hopkins, Amy M.; De Laporte, Laura; Tortelli, Federico; Spedden, Elise; Staii, Cristian; Atherton, Timothy J.; Hubbell, Jeffrey A.; Kaplan, David L.

In: Advanced Functional Materials, Vol. 23, No. 41, 06.11.2013, p. 5140-5149.

Research output: Contribution to journalArticle

Hopkins, AM, De Laporte, L, Tortelli, F, Spedden, E, Staii, C, Atherton, TJ, Hubbell, JA & Kaplan, DL 2013, 'Silk hydrogels as soft substrates for neural tissue engineering', Advanced Functional Materials, vol. 23, no. 41, pp. 5140-5149. https://doi.org/10.1002/adfm.201300435
Hopkins AM, De Laporte L, Tortelli F, Spedden E, Staii C, Atherton TJ et al. Silk hydrogels as soft substrates for neural tissue engineering. Advanced Functional Materials. 2013 Nov 6;23(41):5140-5149. https://doi.org/10.1002/adfm.201300435
Hopkins, Amy M. ; De Laporte, Laura ; Tortelli, Federico ; Spedden, Elise ; Staii, Cristian ; Atherton, Timothy J. ; Hubbell, Jeffrey A. ; Kaplan, David L. / Silk hydrogels as soft substrates for neural tissue engineering. In: Advanced Functional Materials. 2013 ; Vol. 23, No. 41. pp. 5140-5149.
@article{9cccd0e1091d4c148dc95dc2b993b805,
title = "Silk hydrogels as soft substrates for neural tissue engineering",
abstract = "There is great need for soft biomaterials that match the stiffness of human tissues for tissue engineering and regeneration. Hydrogels are frequently employed for extracellular matrix functionalization and to provide appropriate mechanical cues. It is challenging, however, to achieve structural integrity and retain bioactive molecules in hydrogels for complex tissue formation that may take months to develop. This work aims to investigate mechanical and biochemical characteristics of silk hydrogels for soft tissue engineering, specifically for the nervous system. The stiffness of 1 to 8{\%} silk hydrogels, measured by atomic force microscopy, is 4 to 33 kPa. The structural integrity of silk gels is maintained throughout embryonic chick dorsal root ganglion (cDRG) explant culture over 4 days whereas fibrin and collagen gels decrease in mass over time. Neurite extension of cDRGs cultured on 2 and 4{\%} silk hydrogels exhibit greater growth than softer or stiffer gels. Silk hydrogels release <5{\%} of neurotrophin-3 (NT-3) over 2 weeks and 11-day old gels show maintenance of growth factor bioactivity. Finally, fibronectin- and NT-3-functionalized silk gels elicit increased axonal bundling suggesting their use in bridging nerve injuries. These results support silk hydrogels as soft and sustainable biomaterials for neural tissue engineering. Silk hydrogels are soft biomaterials of stiffness matching that of nervous system tissues. Significant chick dorsal root ganglion explant outgrowth is exhibited on 2 to 4{\%} w/v silk hydrogels supplemented with neurotrophic factors exemplifying their employment in extracellular matrix functionalization for neural tissue engineering applications.",
keywords = "biomedical applications, biomimetics, extracellular matrix engineering, hydrogels, tissue engineering",
author = "Hopkins, {Amy M.} and {De Laporte}, Laura and Federico Tortelli and Elise Spedden and Cristian Staii and Atherton, {Timothy J.} and Hubbell, {Jeffrey A.} and Kaplan, {David L.}",
year = "2013",
month = "11",
day = "6",
doi = "10.1002/adfm.201300435",
language = "English",
volume = "23",
pages = "5140--5149",
journal = "Advanced Functional Materials",
issn = "1616-301X",
publisher = "Wiley-VCH Verlag",
number = "41",

}

TY - JOUR

T1 - Silk hydrogels as soft substrates for neural tissue engineering

AU - Hopkins, Amy M.

AU - De Laporte, Laura

AU - Tortelli, Federico

AU - Spedden, Elise

AU - Staii, Cristian

AU - Atherton, Timothy J.

AU - Hubbell, Jeffrey A.

AU - Kaplan, David L.

PY - 2013/11/6

Y1 - 2013/11/6

N2 - There is great need for soft biomaterials that match the stiffness of human tissues for tissue engineering and regeneration. Hydrogels are frequently employed for extracellular matrix functionalization and to provide appropriate mechanical cues. It is challenging, however, to achieve structural integrity and retain bioactive molecules in hydrogels for complex tissue formation that may take months to develop. This work aims to investigate mechanical and biochemical characteristics of silk hydrogels for soft tissue engineering, specifically for the nervous system. The stiffness of 1 to 8% silk hydrogels, measured by atomic force microscopy, is 4 to 33 kPa. The structural integrity of silk gels is maintained throughout embryonic chick dorsal root ganglion (cDRG) explant culture over 4 days whereas fibrin and collagen gels decrease in mass over time. Neurite extension of cDRGs cultured on 2 and 4% silk hydrogels exhibit greater growth than softer or stiffer gels. Silk hydrogels release <5% of neurotrophin-3 (NT-3) over 2 weeks and 11-day old gels show maintenance of growth factor bioactivity. Finally, fibronectin- and NT-3-functionalized silk gels elicit increased axonal bundling suggesting their use in bridging nerve injuries. These results support silk hydrogels as soft and sustainable biomaterials for neural tissue engineering. Silk hydrogels are soft biomaterials of stiffness matching that of nervous system tissues. Significant chick dorsal root ganglion explant outgrowth is exhibited on 2 to 4% w/v silk hydrogels supplemented with neurotrophic factors exemplifying their employment in extracellular matrix functionalization for neural tissue engineering applications.

AB - There is great need for soft biomaterials that match the stiffness of human tissues for tissue engineering and regeneration. Hydrogels are frequently employed for extracellular matrix functionalization and to provide appropriate mechanical cues. It is challenging, however, to achieve structural integrity and retain bioactive molecules in hydrogels for complex tissue formation that may take months to develop. This work aims to investigate mechanical and biochemical characteristics of silk hydrogels for soft tissue engineering, specifically for the nervous system. The stiffness of 1 to 8% silk hydrogels, measured by atomic force microscopy, is 4 to 33 kPa. The structural integrity of silk gels is maintained throughout embryonic chick dorsal root ganglion (cDRG) explant culture over 4 days whereas fibrin and collagen gels decrease in mass over time. Neurite extension of cDRGs cultured on 2 and 4% silk hydrogels exhibit greater growth than softer or stiffer gels. Silk hydrogels release <5% of neurotrophin-3 (NT-3) over 2 weeks and 11-day old gels show maintenance of growth factor bioactivity. Finally, fibronectin- and NT-3-functionalized silk gels elicit increased axonal bundling suggesting their use in bridging nerve injuries. These results support silk hydrogels as soft and sustainable biomaterials for neural tissue engineering. Silk hydrogels are soft biomaterials of stiffness matching that of nervous system tissues. Significant chick dorsal root ganglion explant outgrowth is exhibited on 2 to 4% w/v silk hydrogels supplemented with neurotrophic factors exemplifying their employment in extracellular matrix functionalization for neural tissue engineering applications.

KW - biomedical applications

KW - biomimetics

KW - extracellular matrix engineering

KW - hydrogels

KW - tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=84881255633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881255633&partnerID=8YFLogxK

U2 - 10.1002/adfm.201300435

DO - 10.1002/adfm.201300435

M3 - Article

AN - SCOPUS:84881255633

VL - 23

SP - 5140

EP - 5149

JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-301X

IS - 41

ER -