Limitations
There are several limitations to our study beyond those noted above. First, evaluation was done on a limited number of hearts. Thus, consistency in results across larger sample sizes needs to be evaluated. Second, these studies reflected acute evaluations of changes in conduction both post-ablation and post-injection. It is possible that lesion maturation may occur over a longer period of time, resulting in dynamic shifts in cardiac activation that may not have been reflected in the acute state. Third, as stated previously, we could not inject a predictable amount of hydrogel each time due to materials properties not permitting appropriate in-tissue retention. Thus, we could not determine a threshold amount of material that would need to be injected to facilitate some change in conduction. In addition, the approach to the testing and mapping (ex vivo perfused hearts and epicardial only mapping) may not necessarily extend to in vivo examples, and, thus, before further conclusions can be made, in vivo acute and chronic studies will be needed. Finally, we could not evaluate immunogenicity or potential for chronic maintenance of the perceived conduction changes due to the acute and ex vivo nature of the study.
Conclusion Our study shows that novel injectable conductive hydrogel can enhance myocardial conduction through regions of tissue injury. Future studies will need to focus on optimizing rheological, electrical conductivity, and in-situ gel formation properties of the conductive hydrogel such that it can be predictably retained within tissue while maintaining conductive properties. In addition, it will be important to improve understanding of the effect on local conduction not just epicardially but transmurally. Finally, establishing both long-term durability of activation normalization and biocompatibility will be key.