The effect of growth factors on both collagen synthesis and tensile strength of engineered human ligaments

Paul Hagerty, Ann Lee, Sarah Calve, Cassandra A Lee, Martin Vidal, Keith Baar

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Growth factors play a central role in the development and remodelling of musculoskeletal tissues. To determine which growth factors optimized in vitro ligament formation and mechanics, a Box-Behnken designed array of varying concentrations of growth factors and ascorbic acid were applied to engineered ligaments and the collagen content and mechanics of the grafts were determined. Increasing the amount of transforming growth factor (TGF) β1 and insulin-like growth factor (IGF)-1 led to an additive effect on ligament collagen and maximal tensile load (MTL). In contrast, epidermal growth factor (EGF) had a negative effect on both collagen content and MTL. The predicted optimal growth media (50 μg/ml TGFβ, IGF-1, and GDF-7 and 200 μ m ascorbic acid) was then validated in two separate trials: showing a 5.7-fold greater MTL and 5.2-fold more collagen than a minimal media. Notably, the effect of the maximized growth media was scalable such that larger constructs developed the same material properties, but larger MTL. These results show that optimizing the interactions between growth factors and engineered ligament volume results in an engineered ligament of clinically relevant function.

Original languageEnglish (US)
Pages (from-to)6355-6361
Number of pages7
JournalBiomaterials
Volume33
Issue number27
DOIs
StatePublished - Sep 2012

Keywords

  • Ascorbic acid
  • Design of experiments
  • EGF
  • IGF-1
  • Regenerative medicine
  • TGF-beta

ASJC Scopus subject areas

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

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