Most cross-linking methods utilize chemistry or physical processes that are detrimental to cells and tissue development. Those that are not as harmful often do not provide a level of strength that ultimately meets the required application. The purpose of this work was to investigate the use of a ruthenium-sodium persulfate cross-linking system to form dityrosine in fibrin-based engineered tissue. By utilizing the tyrosine residues inherent to fibrin and cell-deposited proteins, at least 3-fold mechanical strength increases and 10-fold stiffness increases were achieved after cross-linking. This strengthening and stiffening effect was found to increase with culture duration prior to cross-linking such that physiologically relevant properties were obtained. Fibrin was not required for this effect as demonstrated by testing with collagen-based engineered tissue. Cross-linked tissues were implanted subcutaneously and shown to have minimal inflammation after 30 days, similar to non-cross-linked controls. Overall, the method employed is rapid, non-toxic, minimally inflammatory, and is capable of increasing strength and stiffness of engineered tissues to physiological levels.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Apr 2011|
Bibliographical noteFunding Information:
The technical assistance of Naomi Ferguson, Ying Lung Lee and Lee Meier is gratefully acknowledged. Implantation procedures were conducted by Chad Burgess of University of Minnesota Experimental Surgical Services and histopathology was provided by Dr. George R. Ruth. This work was supported by the National Institutes of Health ( NHLBI R01 HL083880 to RTT) and 3M Company (JWB). Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program.
- Arterial tissue engineering