Enhanced fibrin remodeling in vitro with TGF-beta1, insulin and plasmin for improved tissue-equivalents.
The aim of this study was to better understand how to increase collagen content in and enhance mechanical properties of tissue-equivalents formed by entrapping tissue cells in fibrin gels, with the ultimate goal of developing mechanically robust artificial tissues. The two main areas of focus were cell culture medium composition and replacement frequency relative to a base case of incubating constructs in medium supplemented with just serum and replaced weekly. The optimal condition involved a combination of all three factors investigated-TGF-beta, insulin, plasmin-with medium replacement three times a week. Compared to a base case without these three factors, the combination case resulted in 20 times more collagen and a ten-fold increase in tensile strength. The high strain modulus and tensile strength were within an order of magnitude of cardiovascular tissues. This study indicates great potential for fibrin-based tissue-equivalents in soft connective tissue applications.
Department of Chemical Engineering & Materials Science and Biomedical Engineering, University of Minnesota, Minneapolis 55455, USA.
M R
MR
Neidert
E S
ES
Lee
T R
TR
Oegema
R T
RT
Tranquillo
D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D003432:Cross-Linking Reagents; D003470:Culture Media; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D005782:Gels; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008422:Materials Testing; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003470:Culture Media; D005782:Gels; D007328:Insulin; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005337:Fibrin; D003094:Collagen; D005341:Fibrinolysin