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.

Development of an iPSC-derived tissue-resident macrophage-based platform for the in vitro immunocompatibility assessment of human tissue engineered matrices

“…Accordingly, iMϕ secretion of IL-6 and IL-1β could be also a result of the xenogeneic protein immunogenicity factor, however, here it is only assessed which is the cumulative effect of the proteomic composition as it would be a more realistic scenario. Moreover, adjusting the culture conditions to xenofree conditions might be beneficial to adjust the proteomic composition during hTEM development 56 . Furthermore, the quantification of residual DNA on the hTEMs has been performed to prove decellularization efficiency as mentioned in the multiscale characterization 9 .…”