Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing

Rosaria Santoro, Andy L. Olivares, Gerben Brans, Dieter Wirz, Cristina Longinotti, Damien Lacroix, Ivan Martin, David Wendt

Research output: Contribution to journalArticlepeer-review

Abstract

Apart from partial or total joint replacement, no surgical procedure is currently available to treat large and deep cartilage defects associated with advanced diseases such as osteoarthritis. In this work, we developed a perfusion bioreactor system to engineer human cartilage grafts in a size with clinical relevance for unicompartmental resurfacing of human knee joints (50 mm diameter × 3 mm thick). Computational fluid dynamics models were developed to optimize the flow profile when designing the perfusion chamber. Using the developed system, human chondrocytes could be seeded throughout large 50 mm diameter scaffolds with a uniform distribution. Following two weeks culture, tissues grown in the bioreactor were viable and homogeneously cartilaginous, with biomechanical properties approaching those of native cartilage. In contrast, tissues generated by conventional manual production procedures were highly inhomogeneous and contained large necrotic regions. The unprecedented engineering of human cartilage tissues in this large-scale opens the practical perspective of grafting functional biological substitutes for the clinical treatment for extensive cartilage defects, possibly in combination with surgical or pharmacological therapies to support durability of the implant. Ongoing efforts are aimed at integrating the up-scaled bioreactor based processes within a fully automated and closed manufacturing system for safe, standardized, and GMP compliant production of large-scale cartilage grafts.

Original languageEnglish
Pages (from-to)8946-8952
Number of pages7
JournalBiomaterials
Volume31
Issue number34
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Bioreactor
  • Cartilage repair
  • Computational fluid dynamics
  • Regenerative medicine
  • Scale-up
  • Tissue engineering

ASJC Scopus subject areas

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

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