@misc{hauser_characterization_of_2019, 
author={Hauser, S., Wodtke, R., Tondera, C., Wodtke, J., Neffe, A., Hampe, J., Lendlein, A., Löser, R., Pietzsch, J.},
title={Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials},
year={2019},
howpublished = {journal article},
doi = {https://doi.org/10.1021/acsbiomaterials.9b01299},
abstract = {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.},
note = {Online available at: \url{https://doi.org/10.1021/acsbiomaterials.9b01299} (DOI). Hauser, S.; Wodtke, R.; Tondera, C.; Wodtke, J.; Neffe, A.; Hampe, J.; Lendlein, A.; Löser, R.; Pietzsch, J.: Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials. ACS Biomaterials Science & Engineering. 2019. vol. 5, no. 11, 5979-5989. DOI: 10.1021/acsbiomaterials.9b01299}}