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Biomaterials. 2017 Jul;133:132-143. doi: 10.1016/j.biomaterials.2017.04.015. Epub 2017 Apr 14.

Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to the ischemic rat heart.

Author information

1
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
2
Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
3
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
4
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
5
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
6
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: wagnerwr@upmc.edu.

Abstract

Biodegradable and elastomeric patches have been applied to the surface of infarcted hearts as temporary mechanical supports to effectively alter adverse left ventricular remodeling processes. In this report, recombinant adeno-associated virus (AAV), known for its persistent transgene expression and low pathogenicity, was incorporated into elastomeric polyester urethane urea (PEUU) and polyester ether urethane urea (PEEUU) and processed by electrospinning into two formats (solid fibers and core-sheath fibers) designed to influence the controlled release behavior. The extended release of AAV encoding green fluorescent protein (GFP) was assessed in vitro. Sustained and localized viral particle delivery was achieved over 2 months in vitro. The biodegradable cardiac patches with or without AAV-GFP were implanted over rat left ventricular lesions three days following myocardial infarction to evaluate the transduction effect of released viral vectors. AAV particles were directly injected into the infarcted hearts as a control. Cardiac function and remodeling were significantly improved for 12 weeks after patch implantation compared to AAV injection. More GFP genes was expressed in the AAV patch group than AAV injection group, with both α-SMA positive cells and cardiac troponin T positive cells transduced in the patch group. Overall, the extended release behavior, prolonged transgene expression, and elastomeric mechanical properties make the AAV-loaded scaffold an attractive option for cardiac tissue engineering where both gene delivery and appropriate mechanical support are desired.

KEYWORDS:

AAV; Cardiac patch; Electrospun scaffold; Gene delivery; Myocardial infarction

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