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Controlled delivery of nitric oxide in cardiovascular tissue engineering

Qiang Zhao1, Zhihong Wang1*, Jimin Zhang1 and Deling Kong1
  • 1 Nankai University, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, China

Nitric oxide (NO) is an important signaling molecule in the cardiovascular system. NO secreted by the endothelium holds important physiological function in maintaining the vessel patency and promoting tissue regeneration. Our group has previously prepared polysaccharide- and peptide- hydrogel based NO-releasing biomaterials by conjugation of glycosylated NO donors, which are highly stable and only decompose to release NO under the catalysis of corresponding enzymes, glycosidases. The two biomaterials showed significant effect in treatment of mouse hindlimb ischemia and skin injury. They can also be used as carrier for the delivery of stem cells, and improved therapeutic efficacy was observed in mouse myocardial infarction model by increasing cell engraftment and angiogenic paracrine action. In addition, we put forward a new concept that the enzyme immobilized on the vascular graft can catalyze exogenously supplied prodrug to release NO locally and sustainedly. In vivo implantation by replacing rat abdominal aorta demonstrated that localized NO release improved tissue regeneration, remodeling, as well as physiological function, which are critical for the small-diameter vascular grafts to maintain long-term patency.

The work was financially supported by NSFC projects (No. 81171478, 81371699, and 81522023).

References:
[1] Liu VWT, Huang P. Cardiovascular roles of nitric oxide: A review of insights from nitric oxide synthase gene disrupted mice. Cardiovasc Res 2008,77:19-29.
[2] Zhao Q, Zhang J, Song LJ, Ji Q, Yao Y, Cui Y, Shen J*, Wang PG, Kong D*. Polysaccharide-based biomaterials with on-demand nitric oxide releasing property regulated by enzyme catalysis. Biomaterials 2013, 34: 8450-8.
[3] Gao J, Zheng W, Zhang J, Guan D, Yang Z*, Kong D, Zhao Q*. Enzyme-controllable delivery of nitric oxide from a molecular hydrogel. Chem Commun 2013, 49:9173-5.
[4] Yao X, Liu Y, Gao J, Yang L, Mao D, Stefanitsch C, Li Y, Zhang J, Ou L, Kong D, Zhao Q*, Li Z*. Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction. Biomaterials 2015, 60: 130-40.
[5] Wang Z, Lu Y, Qin K, Tian Y, Wang J, Zhang J, Cui Y, Wu Y, Hou J, Shen J, Xu Q, Kong D, Zhao Q*. Enzyme-functionalized vascular grafts catalyze in-situ release of nitric oxide from exogenous NO prodrug. J Control Release 2015, 210: 179-88.

Keywords: blood vessel, Tissue Regeneration, Bioactive molecule, targeting delivery

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: Poster

Topic: Biomaterials to modulate biological processes involved in host response

Citation: Zhao Q, Wang Z, Zhang J and Kong D (2016). Controlled delivery of nitric oxide in cardiovascular tissue engineering. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01323

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Received: 27 Mar 2016; Published Online: 30 Mar 2016.

* Correspondence: Dr. Zhihong Wang, Nankai University, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Tianjin, China, Email1