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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\u2010healing 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\u2010inhibiting C3 toxin, C2IN\u2010C3lim\u2010G205C. This toxin selectively targets osteoclasts and inhibits Rho\u2010signaling and, thereby, actin\u2010dependent processes in these cells. Application of C2IN\u2010C3lim\u2010G205C toxin\u2010loaded hydrogels effectively reduces osteoclast formation and resorption activity in vitro, as demonstrated by tartrate\u2010resistant acid phosphatase staining and the pit resorption assay. Simultaneously, osteoblast activity, viability, and proliferation are unaffected, thus making C2IN\u2010C3lim\u2010G205C toxin\u2010loaded hybrid hydrogels an attractive pharmacological system for spatial and selective modulation of osteoclast functions to reduce bone resorption.<\/jats:p>","DOI":"10.1002\/adhm.201700392","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T08:08:41Z","timestamp":1501488521000},"source":"Crossref","is-referenced-by-count":75,"title":["Spatiotemporally Controlled Release of Rho\u2010Inhibiting C3 Toxin from a Protein\u2013DNA Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity"],"prefix":"10.1002","volume":"6","author":[{"given":"Jasmina","family":"Ga\u010danin","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry III University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kovtun","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics Trauma Research Center University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Schwager","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Quambusch","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry III University of Ulm  89081 Ulm Germany"},{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seah Ling","family":"Kuan","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry III University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Boldt","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry III University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education Department of Chemistry Tsinghua University  100084 Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education Department of Chemistry Tsinghua University  100084 Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education Department of Chemistry Tsinghua University  100084 Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhou","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry III University of Ulm  89081 Ulm Germany"},{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"},{"name":"School of Chemistry and Chemical Engineering Huazhong University of Science and Technology  430074 Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Weil","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry III University of Ulm  89081 Ulm Germany"},{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Barth","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Ignatius","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics Trauma Research Center University of Ulm  89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"e_1_2_7_1_1","first-page":"101","volume":"13","author":"Buza J. 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