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Int J Pharm. 2016 Nov 20;513(1-2):332-346. doi: 10.1016/j.ijpharm.2016.09.045. Epub 2016 Sep 14.

Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model.

Author information

1
Departamento de Zootecnia, Universidade de Évora, Pólo da Mitra, Apartado 94, 7002-554, Évora, Portugal; Instituto de Ciências Agroambientais Mediterrânicas (ICAAM), Pólo da Mitra, Apartado 94, 7002-554, Évora, Portugal.
2
Departamento de Patologia e de Imunologia Molecular, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto (UP), Rua Alfredo Allen, 4200-135 Porto, Portugal.
3
Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Praça Gomes Teixeira, Apartado 55142, 4051-401, Porto, Portugal; Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal; CEMUC, Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
4
Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Praça Gomes Teixeira, Apartado 55142, 4051-401, Porto, Portugal; Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
5
Departamento de Patologia e de Imunologia Molecular, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
6
Internvet, Rua Academia Recreativa Santo Amaro, n° 13, 1300-001 Lisboa, Portugal.
7
Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto (UP), Rua do Campo Alegre, N°. 823, 4150 Porto, Portugal.
8
CEMUC, Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
9
Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Praça Gomes Teixeira, Apartado 55142, 4051-401, Porto, Portugal.
10
Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Praça Gomes Teixeira, Apartado 55142, 4051-401, Porto, Portugal; Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal. Electronic address: ana.colette@hotmail.com.

Abstract

The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.

KEYWORDS:

Dextran; Mesenchymal stem cells; Ovine model; PVA; Synthetic small diameter vascular graft

PMID:
27639624
DOI:
10.1016/j.ijpharm.2016.09.045
[Indexed for MEDLINE]

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