Nerve regeneration following spinal cord injury using matrix metalloproteinase-sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain-derived neurotrophic factor

Jonghyuck Park, Eunjeong Lim, Seungkeun Back, Heung Sik Na, Yongdoo Park, Kyung Sun

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Spinal cord injury leads to the permanent loss of motor and sensory function in the body. To enhance spinal cord regeneration, we used a hyaluronic acid-based hydrogel as a three-dimensional biomimetic scaffold for peptides and growth factors. Three components were used to provide guidance cues: a matrix metalloproteinase peptide crosslinker, an IKVAV (Ile- Lys-Val-Ala-Val) peptide derived from laminin, and brain-derived neurotrophic factor (BDNF). Human mesenchymal stem cells (hMSCs) were cultured in hydrogels in vitro for 10 days to induce neuronal differentiation of hMSCs. Based on gene-expression data, the matrix metalloproteinase-sensitive peptide, IKVAV peptide, and BDNF were critical in the differentiation of hMSCs. Remodeling activity was found to be a key factor in guiding neural differentiation of stem cells. To test this approach in vivo, we used the spinal cord injured rat model and five different hydrogel compositions. Samples were injected into the intrathecal space, and animals were monitored for 6 weeks. Compared to all other groups, animals injected with BDNF-containing hydrogels showed the greatest improvement on locomotive tests (Basso-Beattie-Bresnahan score) during the initial stage after injury. These results suggest that hyaluronic acid-based hydrogels containing IKVAV and BDNF create microenvironments that foster differentiation of stem cells along the neural cell lineage, and they could be used to facilitate nerve regeneration after spinal cord injury.

Original languageEnglish
Pages (from-to)1091-1099
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume93
Issue number3
DOIs
Publication statusPublished - 2010 Jun 1

Fingerprint

Hyaluronic acid
isoleucyl-lysyl-valyl-alanyl-valine
Hydrogel
Brain-Derived Neurotrophic Factor
Biomimetics
Hyaluronic Acid
Scaffolds (biology)
Stem cells
Matrix Metalloproteinases
Hydrogels
Peptides
Brain
Animals
Locomotives
Laminin
Gene expression
Rats
Intercellular Signaling Peptides and Proteins
Nerve Growth Factors
Metalloproteases

Keywords

  • Hyaluronic acid
  • Matrix metalloproteinase
  • Nerve regeneration
  • Spinal cord injury
  • Tissue remodeling

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this

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abstract = "Spinal cord injury leads to the permanent loss of motor and sensory function in the body. To enhance spinal cord regeneration, we used a hyaluronic acid-based hydrogel as a three-dimensional biomimetic scaffold for peptides and growth factors. Three components were used to provide guidance cues: a matrix metalloproteinase peptide crosslinker, an IKVAV (Ile- Lys-Val-Ala-Val) peptide derived from laminin, and brain-derived neurotrophic factor (BDNF). Human mesenchymal stem cells (hMSCs) were cultured in hydrogels in vitro for 10 days to induce neuronal differentiation of hMSCs. Based on gene-expression data, the matrix metalloproteinase-sensitive peptide, IKVAV peptide, and BDNF were critical in the differentiation of hMSCs. Remodeling activity was found to be a key factor in guiding neural differentiation of stem cells. To test this approach in vivo, we used the spinal cord injured rat model and five different hydrogel compositions. Samples were injected into the intrathecal space, and animals were monitored for 6 weeks. Compared to all other groups, animals injected with BDNF-containing hydrogels showed the greatest improvement on locomotive tests (Basso-Beattie-Bresnahan score) during the initial stage after injury. These results suggest that hyaluronic acid-based hydrogels containing IKVAV and BDNF create microenvironments that foster differentiation of stem cells along the neural cell lineage, and they could be used to facilitate nerve regeneration after spinal cord injury.",
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AU - Lim, Eunjeong

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AU - Na, Heung Sik

AU - Park, Yongdoo

AU - Sun, Kyung

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