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Genipin enhances the mechanical properties of tissue‐engineered cartilage and protects against inflammatory degradation when used as a medium supplement
Author(s) -
Lima Eric G.,
Tan Andrea R.,
Tai Timon,
Marra Kacey G.,
DeFail Alicia,
Ateshian Gerard A.,
Hung Clark T.
Publication year - 2008
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32305
Subject(s) - genipin , extracellular matrix , materials science , cartilage , scaffold , tissue engineering , biomedical engineering , glycosaminoglycan , biophysics , matrix (chemical analysis) , chitosan , biochemistry , composite material , chemistry , anatomy , biology , medicine
Genipin is a naturally‐derived biocompatible cross‐linking agent commonly used to generate three dimensional tissue‐engineered scaffolds or to fix biologically derived scaffolds prior to implantation. Here we propose a novel use for genipin as a long‐term culture medium supplement to promote cross‐linking of de novo cell products that are produced in engineered cartilage. We hypothesize that the application of genipin will stabilize the extracellular matrix components and increase the mechanical properties of developing engineered cartilage. Chondrocytes encapsulated in agarose hydrogel (a neutrally charged polysaccharide scaffold that is unaffected by genipin cross‐linking) were cultured in a chemically‐defined growth medium that was supplemented with varying concentrations of genipin (22 μM, 220 μM, 2200 μM) for various durations (continuous or intermittent). Tissues developed significantly higher mechanical properties (+28% dynamic modulus and +20% Young's modulus) by day 42 with genipin treatment compared to untreated controls. These increases were not immediate, but presented over culture time after genipin treatment. The genipin treated groups were also more resistant to cytokine‐induced degradation with interleukin‐1α; maintaining an E Y (+218%), G• (+390%) and glycosaminoglycan (GAG) content (+477%) over genipin‐untreated constructs subjected to interleukin. We hypothesize two mechanisms through which the physical enhancement of tissue properties may be fostered: (1) by cross‐link mediated reorganization and enhanced retention of cell‐elaborated extracellular matrix components, and (2) through reduction of the loss of extracellular matrix components by increasing their resilience to catabolic degradation. These studies demonstrate a potential use of genipin as a medium supplement to develop enhanced engineered cartilage. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009