Xenogeneic Serum-Free Human Cell-Derived Tissue Engineered Matrices for the Development of Clinical-Grade Biomimetic Cardiovascular Devices

Abstract

The development of next-generation biomimetic cardiovascular implants using tissue engineering concepts can address the existing shortcomings of the clinically available prostheses, offering the possibility to generate life-long, native-analogous constructs with self-remodeling and regenerative capacities. Scaffolds for tissue-engineered cardiovascular prostheses can be obtained from allogenic cell sources, that can then produce human tissue-engineered matrices (hTEMs) in vitro. Traditionally, fetal bovine serum (FBS) is used as a universal cell growth supplement. However, concerns regarding its biosafety remain a challenge for clinical translation. The aim of this study is to develop a novel xenogeneic serum-free approach for the manufacturing of clinical grade hTEMs. To achieve this, decellularized hTEMs are generated under xenogeneic serum-free conditions and have subsequently demonstrated hTEMs perform similarly to the FBS-supplemented control group in terms of extracellular matrix (ECM) composition, hemocompatibility, thrombogenicity, and calcification potential. Finally, the xenogeneic serum-free protocol is successfully adapted to the development of hTEM-based tissue-engineered heart valves for the systemic circulation, showing proof-of-concept functionality in vitro. Overall, the data suggest the effectiveness of xenogeneic serum-free culture method as a valid alternative to FBS for the production of hTEM for cardiovascular applications.