Next-generation transcatheter aortic valve implantation

Area of Science:

• Biomaterials Science
• Cardiovascular Engineering
• Immunology

Background:

• Transcatheter aortic valve implantation (TAVI) is increasingly used, but tissue valve durability and complications remain concerns.
• Immune reactions to α-Gal and calcification limit current cardiac xenograft efficacy.
• Next-generation TAVI requires α-Gal-free xenografts, anticalcification therapies, and advanced manufacturing for improved outcomes.

Purpose of the Study:

• To develop and evaluate a next-generation TAVI system using α-Gal-free xenografts and 3D printing technology.
• To assess the preclinical safety, efficacy, and durability of this novel TAVI approach.
• To mitigate immune rejection and calcification while enhancing procedural safety.

Main Methods:

• Porcine pericardia were decellularized and treated with α-galactosidase to create α-Gal-free xenografts.
• Anticalcification therapies including space filling and crosslinking were applied.
• A sheep-specific nitinol stent backbone was fabricated using 3D printing for a customized aortic root stent.
• A self-expandable stented valve was assembled and tested in vitro before implantation in 9 sheep for preclinical evaluation.

Main Results:

• The novel TAVI valve demonstrated good in vitro performance with excellent stent fit and coronary flow.
• Post-TAVI sheep showed good hemodynamic status and aortic valve function up to 238 days.
• Immunological, radiographic, microscopic, and biochemical analyses confirmed the absence of α-Gal immune reaction and calcification in the xenografts.

Conclusions:

• Preclinical safety and efficacy of the next-generation α-Gal-free TAVI system were successfully demonstrated.
• The combination of α-Gal-free xenografts, anticalcification therapies, and 3D printing offers a promising solution for improved TAVI.
• Further clinical studies are warranted to translate these findings into patient care.