PB1257 - Custodiol Solution Improves Hemocompatibility of Decellularized Liver Scaffold

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Marlon L. Dias, PhD

PhD Student
Instituto 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

Co-Author(s)

BP

Bruno Paranhos

PhD Student
Instituto 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
JF

Juliana Ferreira

Master's student
Instituto 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
Roberto J C Fonseca

Professor
Instituto 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
CB

Cíntia Batista

Undergraduate student
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
Rio de Janeiro, Rio de Janeiro, Brazil
RM

Ricardo Martins-Santos

Undergraduate student
Instituto 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
CA

Cherley Andrade

Researcher
Departamento de Histologia e Embriologia, Universidade do Estado do Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil
LF

Lanuza Faccioli

Postdoctoral Researcher
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
Pittsburgh, Pennsylvania, United States
AS

Alexandre Silva

Professor of Surgery
Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil
FN

Fábio Nogueira

Associate Professor
Laboratório de Proteômica /LADETEC, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil
GD

Gilberto Domont

Emeritus professor
Laboratório de Proteômica /LADETEC, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil
RG

Regina Goldenberg

Full professor
Instituto 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

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.