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-α 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.