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Custodiol Solution Improves Hemocompatibility of Decellularized Liver Scaffold

1Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, INCT-REGENERA, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brasil, Rio de Janeiro, Rio de Janeiro, Brazil, 2Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Brasil, Rio de Janeiro, Rio de Janeiro, Brazil, 3Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil, Rio de Janeiro, Rio de Janeiro, Brazil, 4Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil., Rio de Janeiro, Rio de Janeiro, Brazil, 5Departamento de Histologia e Embriologia, Universidade do Estado do Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brasil, Rio de Janeiro, Rio de Janeiro, Brazil, 6Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA, Pittsburgh, Pennsylvania, United States, 7Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil, Rio de Janeiro, Rio de Janeiro, Brazil, 8Laboratório de Proteômica /LADETEC, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil, Rio de Janeiro, Rio de Janeiro, Brazil

Abstract Number: PB1257

Meeting: ISTH 2022 Congress

Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Blood Cells and Vessel Wall

Background: Organ decellularization is one of the most promising approaches of tissue engineering to overcome the shortage of organs available for transplantation. However, there are key hurdles that still hinder its clinical application, and the lack of hemocompatibility of decellularized materials is a central one.

Aims: In this work, we aimed to evaluate whether Custodiol (HTK solution), a common solution used in organ transplantation, can reduce the thrombogenicity of decellularized liver scaffolds (DLS).

Methods: To reach this aim Wistar rat livers were transferred to be perfused through the portal vein using an infusion pump at 3 ml/min with water for 2 hours followed by 1% Triton X-100 for 2 hours and SDS 1% for 18h. Then, we performed ex vivo DLS blood perfusion (n=6), coagulation assays (n=3), platelets aggregation assays (n=3), recellularization (n=3), proteomic analysis (n=6), and in vivo transplantation (n=6). All data were described as means ± standard deviations (SD). The comparison between groups was performed using a paired Student’s t-test or one-way ANOVA with Tukey’s multiple comparisons test.

Results: In this work, we demonstrate that Custodiol increased the hemocompatibility of DLS obtained from rat livers. We showed that Custodiol inhibited ex vivo, in vitro, and in vivo blood coagulation to such extent that allowed successful transplantation of whole-liver scaffolds into recipient animals. DLS previously perfused with Custodiol showed no signs of platelet aggregation and maintained in vitro and in vivo cellular compatibility. Proteomic analysis revealed that proteins related to platelet aggregation were reduced in Custodiol samples while control samples were enriched with thrombogenicity-related proteins. We also identified distinct components that could potentially be involved with this anti-thrombogenic effect and thus require further investigation.

Conclusion(s): Therefore, Custodiol perfusion emerge as a promising strategy to reduce the thrombogenicity of decellularized biomaterials and could benefit several applications of whole-organ tissue engineering.

Image

Decellularized Liver Scaffold obtained after rat liver decellularization process with water, Triton X-100 1% and Sodium Dodecyl Sulfate 1%.

Image

Gross appearance of the Decellularized Liver Scaffold after 1h of perfusion with blood diluted in Custodiol.

To cite this abstract in AMA style:

Dias M, Paranhos B, Ferreira J, Fonseca R, Batista C, Martins-Santos R, Andrade C, Faccioli L, Silva A, Nogueira F, Domont G, Goldenberg R. Custodiol Solution Improves Hemocompatibility of Decellularized Liver Scaffold [abstract]. https://abstracts.isth.org/abstract/custodiol-solution-improves-hemocompatibility-of-decellularized-liver-scaffold/. Accessed September 29, 2023.

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