Spatiotemporally Controlled Release of Rho-Inhibiting C3 Toxin from a Protein-DNA Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity
| العنوان: | Spatiotemporally Controlled Release of Rho-Inhibiting C3 Toxin from a Protein-DNA Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity |
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| المؤلفون: | Weina Liu, Holger Barth, Victoria Schwager, Zhongqiang Yang, Chuang Li, Stephan Fischer, Anna Kovtun, Anita Ignatius, Felix Boldt, Jasmina Gačanin, Seah Ling Kuan, Dongsheng Liu, Johanna Quambusch, Yuzhou Wu, Tanja Weil |
| المساهمون: | European Union (EU), Horizon 2020 |
| المصدر: | Advanced Healthcare Materials |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Botulinum Toxins, Pharmaceutical Science, Osteoclasts, Bone resorption, NAD-ADP-Ribosyltransferase, 02 engineering and technology, Bone tissue, Polyethylene Glycols, Clostridial Rho-inhibiting C3 toxin, ADP Ribose Transferases, rho-Associated Kinases, Osteoblast, Cell Differentiation, Hydrogels, Vertebroplastie, 021001 nanoscience & nanotechnology, Controlled release, Drug delivery systems, Resorption, Cell biology, medicine.anatomical_structure, Drug delivery, Self-healing hydrogels, 0210 nano-technology, Rheology, Signal Transduction, Materials science, Cell Survival, Cells, Recombinant Fusion Proteins, Biomedical Engineering, Growths, Cell Line, Biomaterials, 03 medical and health sciences, Matrigel, Osteoclast, medicine, Animals, Humans, ddc:610, Prophylactic vertebroplasty, Serum Albumin, Chitosan, Osteoblasts, Osteolyse, Macrophages, DNA, Rekombinantes Protein, Recombinant human dnase, 030104 developmental biology, Mutagenesis, Site-Directed, Osteoporosis, DDC 610 / Medicine & health, Biomedical engineering |
| الوصف: | In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks. The hybrid hydrogel combines advantageous characteristics, including rapid gelation through DNA hybridization under physiological conditions and a self-healing and injectable nature with the possibility of specific loading and spatiotemporally controlled release of active proteins, making it an advanced biomaterial for the local treatment of bone diseases, for example, osteoporosis. The hydrogels are loaded with a recombinant Rho-inhibiting C3 toxin, C2IN-C3lim-G205C. This toxin selectively targets osteoclasts and inhibits Rho-signaling and, thereby, actin-dependent processes in these cells. Application of C2IN-C3lim-G205C toxin-loaded hydrogels effectively reduces osteoclast formation and resorption activity in vitro, as demonstrated by tartrate-resistant acid phosphatase staining and the pit resorption assay. Simultaneously, osteoblast activity, viability, and proliferation are unaffected, thus making C2IN-C3lim-G205C toxin-loaded hybrid hydrogels an attractive pharmacological system for spatial and selective modulation of osteoclast functions to reduce bone resorption. publishedVersion |
| وصف الملف: | application/pdf |
| تدمد: | 2192-2659 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a836cfaf4a11b99a367b1e3d116e181Test https://pubmed.ncbi.nlm.nih.gov/28758712Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0a836cfaf4a11b99a367b1e3d116e181 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21922659 |
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