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

• Published in: International journal of biological macromolecules 2023-07, Vol.242 (Pt 1), p.124618-124618, Article 124618
• Main Authors: Wang, Xu, Gu, Zhipeng, Wan, Junyu, Zhou, Xiong, Zhu, Keli, Wang, Xin, Cao, Xin, Yu, Xixun, Peng, Xu, Tang, Yong
• Format: Article
• Language: English
• Subjects: Adenosine - chemistry; Adenosine related enzyme; Blood Vessel Prosthesis; Humans; Inflammation; Macrophages; Oxidized chondroitin sulfate; Self-controlled antiinflammation
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.124618

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. Biomedical material that can automatically control the release of adenosine to ensure long-term patency of blood vessels after transplantation. [Display omitted] •A novel pH&T dual-responsive OCSA/APY/ACP-dECM blood vessel was prepared.•Inflammatory micro-environment of anastomotic stoma activated the ADO related enzyme.•APY/ACP enzymes ensured ADO release in an appropriate active range (10 nM ∼ 1 mM).•ADO secretion avoided rapid occlusion to ensured long-term patency of blood vessel.