TY  - JOUR
A1  - Hauser, Sandra
A1  - Wodtke, Robert
A1  - Tondera, Christoph
A1  - Wodtke, Johanna
A1  - Neffe, Axel T.
A1  - Hampe, Jochen
A1  - Lendlein, Andreas
A1  - Löser, Reik
A1  - Pietzsch, Jens
T1  - Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials
JF  - ACS biomaterials science & engineering
N2  - Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial-tissue interactions due to its presence and versatile functions in the extracellular environment. TGase 2 catalyzes the cross-linking of proteins through its Ca2+-dependent acyltransferase activity. Moreover, it enhances the interactions between fibronectin and integrins, which in turn mediates the adhesion, migration, and motility of the cells. TGase 2 is also a key player in the pathogenesis of fibrosis. In this study, we investigated whether TGase 2 is present at the biomaterial tissue interface and might serve as an informative biomarker for the visualization of tissue response toward gelatin-based biomaterials. Two differently cross-linked hydrogels were used, which were obtained by the reaction of gelatin with lysine diisocyanate ethyl ester. The overall expression of TGase 2 by endothelial cells, macrophages, and granulocytes was partly influenced by contact to the hydrogels or their degradation products, although no clear correlation was evidenced. In contrast, the secretion of TGase 2 differed remarkably between the different cells, indicating that it might be involved in the cellular reaction toward gelatin-based hydrogels. The hydrogels were implanted subcutaneously in immunocompetent, hairless SKH1-Elite mice. Ex vivo immunohistochemical analysis of tissue sections over 112 days revealed enhanced expression of TGase 2 around the hydrogels, in particular at days 14 and 21 post-implantation. The incorporation of fluorescently labeled cadaverine derivatives for the detection of active TGase 2 was in accordance with the results of the expression analysis. The presence of an irreversible inhibitor of TGase 2 led to attenuated incorporation of the cadaverines, which verified the catalytic action of TGase 2. Our in vitro and ex vivo results verified TGase 2 as a potential biomarker for tissue response toward gelatin-based hydrogels. In vivo, no TGase 2 activity was detectable, which is mainly attributed to the unfavorable physicochemical properties of the cadaverine probe used.
KW  - extracellular matrix modifying enzymes
KW  - gelatin-based hydrogels
KW  - biomaterial-tissue interface
KW  - polyamines
KW  - optical imaging
Y1  - 2019
U6  - https://doi.org/10.1021/acsbiomaterials.9b01299
SN  - 2373-9878
VL  - 5
IS  - 11
SP  - 5979
EP  - 5989
PB  - American Chemical Society
CY  - Washington
ER  -