The effect of growth factors on both collagen synthesis and tensile strength of engineered human ligaments.
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 μM 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.
Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA 95616, USA.
Paul
P
Hagerty
Ann
A
Lee
Sarah
S
Calve
Cassandra A
CA
Lee
Martin
M
Vidal
Keith
K
Baar
D002452:Cell Count; D003094:Collagen / Q000096:biosynthesis*; D003470:Culture Media / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008022:Ligaments / Q000187:drug effects* / Q000502:physiology*; D008422:Materials Testing; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D015203:Reproducibility of Results; D013718:Tensile Strength / Q000187:drug effects*; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D003470:Culture Media; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D005337:Fibrin; D003094:Collagen