dECM based dusal-responsive vascular graft with enzyme-controlled adenine release for long-term patency

Rapid occlusion is the culprit leading to implantation failure of biological blood vessels. Although adenosine is a clinical-proven drug to overcome the problem, its short half-life and turbulent burst-release limit its direct application. Thus, a pH/temperature dual-responsive blood vessel possessed controllable long-term adenosine secretion was constructed based on acellular matrix via compact crosslinking by oxidized chondroitin sulfate (OCSA) and functionalized with apyrase and acid phosphatase. These enzymes, as adenosine micro-generators, controlled the adenosine release amount by real-time-responding to acidity and temperature of vascular inflammation sites. Additionally, the macrophage phenotype was switched from M1 to M2, and related factors expression proved that adenosine release was effectively regulated with the severity of inflammation. What's more, the ultra-structure for degradation resisting and endothelialization accelerating was also preserved by their double-crosslinking. Therefore, this work suggested a new feasible strategy providing a bright future of long-term patency for transplanted blood vessels.

Automated summary

A pH/temperature dual-responsive blood vessel was constructed by crosslinking acellular matrix with oxidized chondroitin sulfate (OCSA), allowing for controllable long-term adenosine secretion. The adenosine release was controlled by enzymes (apyrase and acid phosphatase) that responded to acidity and temperature of vascular inflammation sites in real-time. The double crosslinking preserved the ultrastructure for degradation resistance and accelerated endothelialization. This work suggests a promising strategy for achieving long-term patency in transplanted blood vessels.