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.

A large proportion of cerebral strokes disrupt descending commands from motor cortical areas to the spinal cord which can results in permanent motor de cits of the arm and hand1,2. However, below the lesion, the spinal circuits that control movement5 remain intact and could be targeted by neurotechnologies to restore movement6-9. Here we demonstrate that by engaging spinal circuits with targeted electrical stimulation we immediately improved voluntary motor control in two participants with chronic post-stroke hemiparesis. We implanted a pair of 8-contact percutaneous epidural leads on the lateral aspect of the cervical spinal cord to selectively target the dorsal roots that provide excitatory inputs to motoneurons controlling the arm and hand10,11. With this strategy, we obtained independent activation of shoulder, elbow and hand muscles. Continuous stimulation through selected contacts at speci c frequencies enabled participants to perform movements that they had been unable to perform for many years. Overall, stimulation improved strength, kinematics, and functional performance.Unexpectedly, both participants retained some of these improvements even without stimulation, suggesting that spinal cord stimulation could be a restorative as well as an assistive approach for upper limb recovery after stroke.

No abstract