S1G shows that a 90% contraction can be produced through this fluid-driven method. When administrated with a fluid medium, folding and expansion is achieved through the compressible solid skeletal inside the heart pouch. A tube was attached to the heart pouch, serving as a refill line for multiple delivery of MSCs. In this system, the cover membrane and the semi-permeable membrane were sealed as a pouch to cover the internal components, which were 5 by 5 mm when expanded and 5 by 1 mm when folded ( Fig. Detailed information on heart pouch fabrication is included in Fig. 1A, the heart pouch was assembled from a cover membrane, a semi-permeable membrane, and a compressible solid skeletal, where the resulting cavity between the two films can be used as an MSCs reservoir. Furthermore, we demonstrated the feasibility of minimally invasive delivery in a swine model.ĭesign and fabrication of the Origami Heart PouchĪs shown in Fig. We tested the pouch’s ability to deliver mesenchymal stem cells in a rodent model of acute myocardial infarction. With the semi-permeable membrane, cells are successfully protected from surroundings to maintain their viability while releasing paracrine factors (such as growth factors and exosomes) to the infarcted site for cardiac repair. Termed as fluid-driven, a contraction can be achieved via the administration of fluid medium, allowing the heart pouch easy access into the pericardial space through minimally invasive surgery. This pouch is composed of a compressible solid skeletal structure, a cover membrane and a semi-permeable membrane. The origami structure allowed minimally invasive delivery of the pouch to the heart with two small incisions and can be refilled with the therapeutic of choice. To address these limitations, we developed a fluid-driven heart pouch with a memory-shaped microfabricated lattice structure inspired by origami. Lastly, this technique was only tested in a small animal model. Additionally, suturing was required for securing the reservoir to the heart. 32 However, open-chest surgery was still required for placement of this reservoir. pioneered a replenishable epicardial reservoir, which enabled refillable of mesenchymal stem cells (MSCs) to ischemic cardiac tissue. 26, 27, 28 Furthermore, repeated dosing would not be possible due to the invasive nature of such procedures. 22, 23, 24, 25 However, open-chest surgery is normally required for the implantation of cardiac patches, limiting its use to mild-to-moderate MI patients. 19, 20, 21 Cardiac patch is a promising way to delivery therapeutics with great cardiac retention. 15, 16, 17, 18 Direct muscle injection yields better drug retention in the heart but is still sub-optimal as injected therapeutics and cells are quickly lost due to venous drainage. Intravenous and intracoronary injections have close to zero cardiac retention after 24 hours. 10, 11 Due to the poor proliferation of cardiomyocytes after MI, and the human heart’s lack of spontaneous regeneration, 12, 13, 14 cardiac repair after damage remains an important challenge.Ĭurrent drug delivery to the heart is limited. 8, 9 During MI, fibrous scar tissue gradually takes the place of damaged myocardium, causing eventual loss of ventricular function. 5, 6, 7 The pathology of myocardial infarction is defined by myocardial cell death with a lesser degree from apoptosis, along with pathologic ventricular remodeling. 1, 2, 3, 4 Of note is myocardial infarction (MI), which tends to be undetected until the patient experiences a major complication that can lead to sudden death or severe hemodynamic deterioration. As cardiovascular diseases cause more and more deaths per year, the death rate is expected to reach 23.6 million by 2030.
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