Microneedles in Cardiovascular Disorders

Project Synopsis: 

Scope: Novel drug delivery, Pharmaceutics, Bioengineering Biotechnology, Biopharmaceutics

Cardiovascular disorders are still the primary cause of mortality worldwide (Shi et al., 2020). Although intramyocardial injection can effectively deliver agents to the myocardium, this approach is limited because of its restriction to needle-mediated injection and the minor retention of agents in the myocardium (Shi et al., 2020; Tang et al., 2018). Here, we engineered phase-transition microneedles (MNs) coated with adeno-associated virus (AAV) and achieved homogeneous distribution of AAV delivery (Shi et al., 2020). Bioluminescence imaging revealed the successful delivery and transfection of AAV-luciferase. AAV–green fluorescent protein–transfected cardiomyocytes were homogeneously distributed on postoperative day 28. AAV–vascular endothelial growth factor (VEGF)–loaded MNs improved heart function by enhancing VEGF expression, promoting functional angiogenesis, and activating the Akt signaling pathway (Shi et al., 2020). The results indicated the superiority of MNs over direct muscle injection. Consequently, MNs might emerge as a promising tool with great versatility for delivering various agents to treat ischemic myocardial disease (Lee et al., 2020; Shi et al., 2020; Tang et al., 2018). For the treatment of myocardial infarction, we engineered a microneedle patch integrated with cardiac stromal cells (MN-CSCs) for therapeutic heart regeneration after acute myocardial infarction (MI) (Tang et al., 2018). To perform cell-based heart regeneration, cells are currently delivered to the heart via direct muscle injection, intravascular infusion, or transplantation of epicardial patches (Sun et al., 2021; Tang et al., 2018). The first two approaches suffer from poor cell retention, while epicardial patches integrate slowly with the host myocardium. Here, we used polymeric MNs to create “channels” between the host myocardium and therapeutic CSCs (Sun et al., 2021; Tang et al., 2018). These channels allow regenerative factors secreted by CSCs to be released into the injured myocardium to promote heart repair. In the rat MI model study, the application of the MN-CSC patch effectively augmented cardiac functions and enhanced angiomyogenesis. In the porcine MI model study, MN-CSC patch application was nontoxic and resulted in cardiac function protection (Tang et al., 2018). The MN system represents an innovative approach delivering therapeutic cells for heart regeneration. In another approach, we propose a novel induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs)-integrated conductive microneedle (MN) patch for treating MI (Lee et al., 2020; Tang et al., 2018). The cardiac patches are composed of drug-encapsulated MN bottom layer, parallel-aligned carbon nanotube (CNT) conductive middle layer, and a methacrylated gelatin (GelMA) hydrogel scaffold upper layer. The anisotropic architecture of the MN patches could induce the directional alignment of CMs, while its conductive element could provide a platform for the interaction among cells (Kim et al., 2017). Different from direct stem cell therapeutic patches, the present cardiac patches are utilized for animal tests after inducing the iPSCs to CMs, thus ensuring the orientation of differentiation. It is demonstrated that when applied for MI treatment, the functional MN array patch could firmly adhere to the heart and release the encapsulated drugs to increase the functionality (Sun et al., 2021; Tang et al., 2018). In addition, the existence of an aligned CNT layer not only ensures the simultaneous contraction of CMs distributed on the patch but also makes these cells keep synergies with the heart in vivo. These features make the conductive MN array patches with iPSC-derived CMs integration an ideal therapy strategy for clinical treatment of cardiac diseases (Kim et al., 2017; Lee et al., 2020; Tang et al., 2018).