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

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...

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Bibliographic Details
Published in:Biomaterials 2012-09, Vol.33 (27), p.6355-6361
Main Authors: Hagerty, Paul, Lee, Ann, Calve, Sarah, Lee, Cassandra A, Vidal, Martin, Baar, Keith
Format: Article
Language:English
Subjects:
Advanced Basic Science
Ascorbic acid
Cell Count
Collagen - biosynthesis
Culture Media - chemistry
Dentistry
Design of experiments
EGF
Epidermal Growth Factor - pharmacology
Fibrin - chemistry
Humans
IGF-1
Insulin-Like Growth Factor I - pharmacology
Intercellular Signaling Peptides and Proteins - pharmacology
Ligaments - drug effects
Ligaments - physiology
Materials Testing
Platelet-Derived Growth Factor - pharmacology
Regenerative medicine
Reproducibility of Results
Tensile Strength - drug effects
TGF-beta
Tissue Engineering - methods
Transforming Growth Factor beta1 - pharmacology
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.05.045