Inactivation of human plasma alters the structure and biomechanical properties of engineered tissues Rosell-Valle, Cristina Martín-López, María Campos Sánchez, Fernando Chato Astrain, Jesús Campos Cuerva, Rafael Alaminos Mingorance, Miguel Santos González, Mónica Fibrin agarose hydrogel Tissue engineering Pathogen reduction method Biomechanical properties Bioartificial skin Acknowledgments The authors are grateful to Echevarne Laboratories for the coagulation experiments and to Gloria Carmona and Rosario Sánchez Pernaute as well as all members of the Unidad de Producción y Reprogramación Celular (UPRC) for technical help and support. All figures were created through BioRender.com accessed on 1 September 2021. Funding This research was funded by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i) from Ministerio de Ciencia, Innovación y Universidades (Instituto de Salud Carlos III), grants FIS PI17/0391, RTC-2017- 6658-1, PI20/0317 and ICI19/00024 (BIOCLEFT), co-financed by Fondo Europeo de Desarrollo Regional ERDF-FEDER, European Union and PE-0395-2019 from Consejería de Salud y Familias, Junta de Andalucía, Spain. Fibrin is widely used for tissue engineering applications. The use of blood derivatives, however, carries a high risk of transmission of infectious agents, necessitating the application of pathogen reduction technology (PRT). The impact of this process on the structural and biomechanical properties of the final products is unknown. We used normal plasma (PLc) and plasma inactivated by riboflavin and ultraviolet light exposure (PLi) to manufacture nanostructured cellularized fibrin-agarose hydrogels (NFAHs), and then compared their structural and biomechanical properties. We also measured functional protein C, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and coagulation factors [fibrinogen, Factor (F) V, FVIII, FX, FXI, FXIII] in plasma samples before and after inactivation. The use of PLi to manufacture cellularized NFAHs increased the interfibrillar spacing and modified their biomechanical properties as compared with cellularized NFAH manufactured with PLc. PLi was also associated with a significant reduction in functional protein C, FV, FX, and FXI, and an increase in the international normalized ratio (derived from the PT), APTT, and TT. Our findings demonstrate that the use of PRT for fibrin-agarose bioartificial tissue manufacturing does not adequately preserve the structural and biomechanical properties of the product. Further investigations into PRT-induced changes are warranted to determine the applications of NFAH manufactured with inactivated plasma as a medicinal product. 2022-10-18T09:58:37Z 2022-10-18T09:58:37Z 2022-08-23 journal article Rosell-Valle C, Martín-López M, Campos F, Chato-Astrain J, Campos-Cuerva R, Alaminos M and Santos González M (2022), Inactivation of human plasma alters the structure and biomechanical properties of engineered tissues. Front. Bioeng. Biotechnol. 10:908250. [doi: 10.3389/fbioe.2022.908250] https://hdl.handle.net/10481/77376 10.3389/fbioe.2022.908250 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Frontiers Media