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-β1, 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.
Bibliographical noteFunding Information:
This work has been supported by the NSF MRSEC-Artificial Tissues Program (DMR-9809364). Technical assistance of Erin Grassl and Luca Gunther are also gratefully acknowledged.
- Collagen synthesis
- Fibrin gel
- Tissue engineering