Bovine Primary Chondrocyte Culture in Synthetic Matrix Metalloproteinase-Sensitive Poly(ethylene glycol)-Based Hydrogels as a Scaffold for Cartilage Repair

Yongdoo Park, Matthias P. Lutolf, Jeffrey A. Hubbell, Ernst B. Hunziker, Marcy Wong

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

A poly(ethylene glycol) (PEG)-based hydrogel was used as a scaffold for chondrocyte culture. Branched PEG-vinylsulfone macromers were end-linked with thiol-bearing matrix metalloproteinase (MMP)-sensitive peptides (GCRDGPQGIWGQDRCG) to form a three-dimensional network in situ under physiologic conditions. Both four- and eight-armed PEG macromer building blocks were examined. Increasing the number of PEG arms increased the elastic modulus of the hydrogels from 4.5 to 13.5 kPa. PEG-dithiol was used to prepare hydrogels that were not sensitive to degradation by cell-derived MMPs. Primary bovine calf chondrocytes were cultured in both MMP-sensitive and MMP-insensitive hydrogels, formed from either four- or eight-armed PEG. Most (>90%) of the cells inside the gels were viable after 1 month of culture and formed cell clusters. Gel matrices with lower elastic modulus and sensitivity to MMP-based matrix remodeling demonstrated larger clusters and more diffuse, less cell surface-constrained cell-derived matrix in the chondron, as determined by light and electron microscopy. Gene expression experiments by real-time RT-PCR showed that the expression of type II collagen and aggrecan was increased in the MMP-sensitive hydrogels, whereas the expression level of MMP-13 was increased in the MMP-insensitive hydrogels. These results indicate that cellular activity can be modulated by the composition of the hydrogel. This study represents one of the first examples of chondrocyte culture in a bioactive synthetic material that can be remodeled by cellular protease activity.

Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalTissue Engineering
Volume10
Issue number3-4
DOIs
Publication statusPublished - 2004 Mar 1
Externally publishedYes

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Hydrogels
Ethylene Glycol
Cartilage
Chondrocytes
Matrix Metalloproteinases
Scaffolds
Polyethylene glycols
Repair
Elastic Modulus
Hydrogel
Bearings (structural)
Gels
Elastic moduli
Matrix Metalloproteinase 13
Aggrecans
Collagen Type II
Metalloproteases
Sulfhydryl Compounds
Collagen
Gene expression

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology

Cite this

Bovine Primary Chondrocyte Culture in Synthetic Matrix Metalloproteinase-Sensitive Poly(ethylene glycol)-Based Hydrogels as a Scaffold for Cartilage Repair. / Park, Yongdoo; Lutolf, Matthias P.; Hubbell, Jeffrey A.; Hunziker, Ernst B.; Wong, Marcy.

In: Tissue Engineering, Vol. 10, No. 3-4, 01.03.2004, p. 515-522.

Research output: Contribution to journalArticle

Park, Yongdoo ; Lutolf, Matthias P. ; Hubbell, Jeffrey A. ; Hunziker, Ernst B. ; Wong, Marcy. / Bovine Primary Chondrocyte Culture in Synthetic Matrix Metalloproteinase-Sensitive Poly(ethylene glycol)-Based Hydrogels as a Scaffold for Cartilage Repair. In: Tissue Engineering. 2004 ; Vol. 10, No. 3-4. pp. 515-522.
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