Bioengineered self-seeding heart valves

Abstract

Objective: Mechanical and biological prostheses are used to replace damaged heart valves but are associated with significant morbidities. Although there is increased interest in bioengineering cell-seeded heart valve scaffolds, it is a time-consuming and technically difficult process. The goal of this project was to engineer self-seeding heart valves that mature quickly in vivo and have a shorter preparation time.

Methods: Porcine pulmonary valves were decellularized using detergent methods and then either (1) left untreated (unconjugated, n = 6), (2) reseeded with autologous endothelial progenitor cell-derived endothelial cells (cell-seeded, n = 4), or (3) conjugated with CD133 antibodies (conjugated, n = 8). The valve constructs were transplanted into the pulmonary position of sheep using standard surgical techniques. After 1 or 3 months, the implants were removed and assessed for cell and matrix content as well as biomechanical properties.

Results: Endothelial cells expressing von Willebrand factor lined the entire length of both ventricular and arterial surfaces of conjugated valves by 1 month after implantation. Interstitial cell and structural protein content of conjugated valves increased from 1 month to 3 months with interstitial expression of metalloproteinase-9 and new collagen formation. In contrast, there were few endothelial or interstitial cells associated with unconjugated, or cell-seeded valves at any time point. No calcification or thrombi were noted on any of the valves. Young's modulus and tensile strength was greater in the conjugated valves versus unconjugated or cell-seeded valves.

Conclusions: Results indicate that tissue-engineered heart valve replacement constructs can be made quickly and therefore may be a clinically relevant option for patients needing heart valve surgery in a timely fashion.