Programmable release of 2-O-d-glucopyranosyl-l-ascorbic acid and heparin from PCL-based nanofiber scaffold for reduction of inflammation and thrombosis |
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Authors: | H Wang Y Xia J Liu Z Ma Q Shi J Yin |
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Institution: | 1. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China;2. University of Science and Technology of China, Hefei, Anhui 230026, PR China;3. Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China |
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Abstract: | Reduction of inflammation and thrombosis caused by implanted devices is critical for clinical success. To this end, the strategy based on programmable release of anti-inflammatory and anti-thrombotic agents from the widely-used polycaprolactone (PCL)/gelatin nanofiber scaffold is developed. The release of 2-O-d-Glucopyranosyl-l-ascorbic Acid (AA-2G) and heparin are controlled by reactive oxygen species (ROS)-responsive poly(ethylene glycol)-based β-thioether ester copolymer (PEGDA-EDT) and mesoporous silica nanoparticles (MSN) in the nanofiber, respectively. The in vitro assay demonstrate that the scaffolds are hemocompatible with the resistance of platelet adhesion; the control release of AA-2G prevents initial inflammation and oxidation of the blood cells, and the subsequent release of heparin entitles nanofibers with long-term anti-thrombotic capability. In addition, rapid endothelialization is obtained on the surface of nanofiber scaffolds for the further enhancement of the hemocompatibility. In vivo implant evaluation convinces that the nanofiber scaffolds possess high biocompatibility with the substantial resistance for inflammation and thrombosis. Hence, our work paves a new way to develop the anti-inflammatory and anti-thrombotic tissue-engineering substrates through programmable delivery of two or multiple drugs. |
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Keywords: | Anti-inflammation Anti-thrombosis Phosphatidylserine exposure Hemocompatible surface Rapid endothelialization |
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