Cardioprotection of PLGA/gelatine cardiac patches functionalised with adenosine in a large animal model of ischaemia and reperfusion injury: A feasibility study.
J Tissue Eng Regen Med
; 13(7): 1253-1264, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-31050859
ABSTRACT
The protection from ischaemia-reperfusion-associated myocardial infarction worsening remains a big challenge. We produced a bioartificial 3D cardiac patch with cardioinductive properties on stem cells. Its multilayer structure was functionalised with clinically relevant doses of adenosine. We report here the first study on the potential of these cardiac patches in the controlled delivery of adenosine into the in vivo ischaemic-reperfused pig heart. A Fourier transform infrared chemical imaging approach allowed us to perform a characterisation, complementary to the histological and biochemical analyses on myocardial samples after in vivo patch implantation, increasing the number of investigations and results on the restricted number of pigs (n = 4) employed in this feasibility step. In vitro tests suggested that adenosine was completely released by a functionalised patch, a data that was confirmed in vivo after 24 hr from patch implantation. Moreover, the adenosine-loaded patch enabled a targeted delivery of the drug to the ischaemic-reperfused area of the heart, as highlighted by the activation of the pro-survival signalling reperfusion injury salvage kinases pathway. At 3 months, though limited to one animal, the used methods provided a picture of a tissue in dynamic conditions, associated to the biosynthesis of new collagen and to a non-fibrotic outcome of the healing process underway. The synergistic effect between the functionalised 3D cardiac patch and adenosine cardioprotection might represent a promising innovation in the treatment of reperfusion injury. As this is a feasibility study, the clinical implications of our findings will require further in vivo investigation on larger numbers of ischaemic-reperfused pig hearts.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión Miocárdica
/
Adenosina
/
Copolímero de Ácido Poliláctico-Ácido Poliglicólico
/
Gelatina
/
Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Tissue Eng Regen Med
Asunto de la revista:
BIOTECNOLOGIA
/
HISTOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia