Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 37, Pages 41113-41126Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c12688
Keywords
biological heart valves; erythrocyte membrane; biomimetic drug-loaded nanoparticles; anti-calcification; inflammatory response
Funding
- Interdisciplinary innovation cultivation project of Sichuan University [0900904153015]
- National Natural Science Foundation of China [51703144]
- China Postdoctoral Science Foundation [2018T110976]
- 111 Project (The Program of Introducing Talents of Discipline to Universities) [B16033]
- Sichuan Science and Technology Major Project [2018SZDZX0011]
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In recent years, valvular heart disease has become a serious disease threatening human life and is a major cause of death worldwide. However, the glutaraldehyde (GLU)-treated biological heart valves (BHVs) fail to meet all requirements of clinical application due to disadvantages such as valve thrombus, cytotoxicity, endothelialization difficulty, immune response, and calcification. Encouragingly, there are a large number of carboxyls as well as a few amino groups on the surface of GLU-treated BHVs that can be modified to enhance biocompatibility. Inspired by natural biological systems, we report a novel approach in which the heart valve was cross-linked with erythrocyte membrane biomimetic drug-loaded nanoparticles. Such modified heart valves not only preserved the structural integrity, stability, and mechanical properties of the GLU-treated BHVs but also greatly improved anti-coagulation, anti-inflammation, anti-calcification, and endothelialization. The in vitro results demonstrated that the modified heart valves had long-term anti-coagulation properties and enhanced endothelialization processes. The modified heart valves also showed good biocompatibility, including blood and cell biocompatibility. Most importantly, the modified heart valves reduced the TNF-alpha levels and increased IL-10 compared to GLU-treated BHVs. In vivo animal experiments also confirmed that the modified heart valves had an ultrastrong resistance to calcification after implantation in rats for 120 days. The mechanism of anti-calcification in vivo was mainly due to the controlled release of anti-inflammatory drugs that reduced the inflammatory response after valve implantation. In summary, this therapeutic approach based on BHVs cross-linking with erythrocyte membrane biomimetic nanoparticles sparks a novel design for valvular heart disease therapy.
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