Thrombogenicity Assessment of Perfusable Tissue-Engineered Constructs: A Systematic Review

Abstract

Vascular surgery is facing a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency is particularly applicable to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs is promising as a solution to organ shortage for transplantation. To achieve this, it is essential to (re)construct a biocompatible and nonthrombogenic vascular network within these organs. In this systematic review, we identify, classify, and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue-engineered organs and tissues. We conducted a preregistered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines. This comprised a systematic data extraction, in-depth analysis, and risk of bias assessment of 116 included studies. We identified shaking (n = 28), flow loop (n = 17), ex vivo (arteriovenous shunt, n = 33), and dynamic in vitro models (n = 38) as the main approaches for thrombogenicity assessment. This comprehensive review reveals a prevalent lack of standardization and provides a valuable guide in the design of standardized experimental setups.

Keywords: perfusion; thrombogenicity; tissue engineering; whole blood.