Introduction:
After myocardial infarction (MI), cardiomyocyte death results in a non-contractile fibrotic scar and altered electrical properties, including delayed impulse propagation across the scar region which may contribute to ventricular dysfunction. Hydrogels such as chitosan have been used clinically to stabilize the LV free wall and prevent dilation. We chemically modified chitosan with the charge-carrying conductive polymer polypyrrole (PPy), yielding a biomaterial with more than 100X the conductivity of chitosan alone. Chitosan-PPy is capable of carrying electrical impulses and may enhance synchronous contraction.
Methods:
Biomaterials were synthesized under sterile conditions and were thoroughly characterized
in vitro
. Myocardial infarction was created by coronary artery ligation in Sprague-Dawley rats (n = 36), and 1 week later chitosan, chitosan-PPy or saline were injected into the border zone regions. Animals were followed for 8 or 16 weeks (n = 6/treatment/time-point) and cardiac conduction and function were assessed with ECG, echocardiography, impedance catheter analysis and finally Langendorff-perfused epicardial optical mapping.
Results:
Eight weeks post-injection, QRS duration was increased in saline and chitosan treated hearts, but was maintained in chitosan-PPy hearts until 16 weeks (
p
< 0.01), suggesting less maladaptive ventricular remodeling associated with slowing of depolarizing conduction in the chitosan-PPy group. Echocardiography revealed that fractional shortening was enhanced in chitosan-PPy treated hearts at both 8 and 16 weeks (
p
< 0.01). At 16 weeks, chitosan-PPy hearts had increased stroke work capacity, and better maintained (lower) end systolic volume (
p
< 0.05). Optical mapping demonstrated that chitosan-PPy-treated hearts had faster transverse conduction velocities measured along the border zone epicardial surface (
p
< 0.01).
Conclusions:
We synthesized and characterized a novel conductive polymer hydrogel that may be used therapeutically to enhance favorable cardiac recovery at the LV border zone following an MI. Chitosan-PPy enhanced heart function by augmenting synchronized contraction.
A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct
