Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult due to the nonlinear interaction of excitation waves within a heterogeneous anatomical substrate1–4. Lacking a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation5–7. Here, we establish the relation between the response of the tissue to an electric field and the spatial distribution of heterogeneities of the scale-free coronary vascular structure. We show that in response to a pulsed electric field E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E), and a characteristic time τ for tissue depolarization that obeys a power law τ∝Eα. These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore efficient termination of fibrillation. Using this novel control strategy, we demonstrate, for the first time, low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and at the same time provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.
Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.
Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.
Abstract. Anti-Müllerian hormone (AMH), or Müllerian inhibitory substance, is a hormone that is best known for its production by fetal testes in mammals and as the inhibitor of Müllerian (paramesonephric) duct development in males. However, following the development of the Müllerian ducts into the oviduct, uterus, and upper vagina in female mammals, the ovaries produce AMH, which can be found in measureable amounts within the peripheral circulation, especially in adults. The ovaries appear to be the sole source of AMH in the circulation; therefore, it may be a useful marker in clinically relevant situations when an assessment of the presence or absence of ovaries or ovarian remnants in dogs and cats is important. To that end, a commercially available, human-based assay was evaluated for the measurement of AMH in dogs and cats. A preliminary assessment involved a single test on a set of serum samples from dogs that were submitted to a diagnostic endocrinology laboratory for other tests. Favorable preliminary results led to a more formal assessment of the assay using serum samples from dogs and cats with the presence or absence of the ovaries known by surgical confirmation. Overall, a single measurement of serum AMH concentration was highly effective at distinguishing ovariohysterectomized from intact adult animals. In addition, the assay also accurately identified several cases of ovarian remnant syndrome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.