Mechanisms underlying the synergistic enhancement of self-assembled neocartilage treated with chondroitinase-ABC and TGF-β1

Donald J. Responte, Boaz Arzi, Roman M. Natoli, Jerry C. Hu, Kyriacos A. Athanasiou

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Developing a platform for invitro cartilage formation would enhance the study of cartilage development, pathogenesis, and regeneration. To improve neocartilage formation, our group developed a novel self-assembly process for articular chondrocytes, which has been improved in this study using a novel combination of catabolic and anabolic agents. TGF-β1 was applied in conjunction with the enzyme chondroitinase-ABC (C-ABC) to additively increase tensile properties and synergistically enhance collagen content. Additionally, microarray analysis indicated that TGF-β1 up-regulated MAPK signaling in contrast to C-ABC, which did not enrich genetic pathways. The lack of genetic signaling spurred investigation of the biophysical role of C-ABC, which showed that C-ABC treatment increased collagen fibril diameter and density. After four weeks of culture in nude mice, neocartilage exhibited stability and maturation. This study illustrated an innovative strategy for improving invitro and invivo articular cartilage formation and elucidated mechanisms underlying TGF-β1 and C-ABC treatment.

Original languageEnglish (US)
Pages (from-to)3187-3194
Number of pages8
JournalBiomaterials
Volume33
Issue number11
DOIs
StatePublished - Apr 2012

Keywords

  • Cartilage tissue engineering
  • Collagen
  • Glycosaminoglycan
  • Soft tissue biomechanics

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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