- 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.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.…
MetadatenAuthor details: | Sandra HauserORCiD, Robert Wodtke, Christoph Tondera, Johanna Wodtke, Axel T. NeffeORCiDGND, Jochen HampeORCiD, Andreas LendleinORCiDGND, Reik LöserORCiD, Jens PietzschORCiD |
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DOI: | https://doi.org/10.1021/acsbiomaterials.9b01299 |
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ISSN: | 2373-9878 |
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Title of parent work (English): | ACS biomaterials science & engineering |
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Publisher: | American Chemical Society |
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Place of publishing: | Washington |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2019/11/11 |
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Publication year: | 2019 |
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Release date: | 2021/06/17 |
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Tag: | biomaterial-tissue interface; extracellular matrix modifying enzymes; gelatin-based hydrogels; optical imaging; polyamines |
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Volume: | 5 |
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Issue: | 11 |
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Number of pages: | 21 |
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First page: | 5979 |
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Last Page: | 5989 |
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Funding institution: | Helmholtz AssociationHelmholtz Association; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the Collaborative Research Center Transregio 67 "Functional Biomaterials for Controlling Healing Processes in Bone and Skin - From Material Science to Clinical Application"German Research Foundation (DFG) [CRC/TRR 67/3, 59307082] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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Peer review: | Referiert |
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