Bioresorbable cardiovascular instruments, and operation and fabrication methods of same

#The present invention relates generally to healthcare, and more particularly to a bioresorbable, leadless, battery-free, and fully implantable cardiovascular instruments for control of cardiac rate and rhythm during a stable operating timeframe that subsequently undergoes complete dissolution and clearance via natural biological processes.

#The background description provided herein is for the purpose of generally presenting the context of the invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions. Work of the presently named inventors, to the extent it is described in the background of the invention section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the invention.

#Implantable permanent cardiac pacemakers are the cornerstone of therapy for bradyarrhythmias and atrioventricular (AV) block. As a complement to traditional pacemakers designed as permanent implants, temporary systems provide essential demand-based atrial and/or ventricular pacing for patients where bradyarrhythmias and AV block are expected to be short-lived, such as on the orders of days or weeks. Such devices act as a bridge to permanent pacing therapy or are implemented temporarily following cardiac surgery when post-surgical bradycardia is frequently encountered. Temporary pacing systems include an external generator with one or two transcutaneous pacing leads that are placed, depending on the clinical context, either epicardially or endocardially via a transvenous approach. This hardware, however, carries significant risks of complications. First, bacteria can form biofilms on the foreign materials/devices such as pacing leads, and the transcutaneous access can serve as a route for infections. Second, because the device is not fully implanted, the externalized power supply and control system can be inadvertently dislodged when caring for or mobilizing the patient. Third, removal of temporary transcutaneous devices following completion of therapy can cause laceration and perforation of the myocardium since the pacing leads can become enveloped in fibrotic tissue at the electrode-myocardium interface. These circumstances create a unique need for an alternative temporary pacemaker technology that can deliver the necessary electrotherapy while addressing the associated physiological complications.

#The accompanying drawings illustrate one or more embodiments of the invention and together with the written description, serve to explain the principles of the invention. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.

#FIG. 1 shows materials, design and proposed utilization of a bioresorbable, implantable, leadless, battery-free cardiac pacemaker, according to embodiments of the invention. Panel a: (Left) Schematic illustration of the device mounted on the myocardial tissue. (Middle) The electronic component is composed of three functional parts: i) a wireless receiver, which includes an inductive coil (W/Mg; ~700 nm/~50 μm thick), a radiofrequency PIN diode (Si NM active layer, 320 nm thick), and a dielectric interlayer (PLGA, 50 μm thick) that acts as a power harvester and control interface; ii) flexible extension electrodes (W/Mg; ~700 nm/~50 μm thick); and iii) a contact pad with exposed electrodes at the ends to interface with the myocardial tissue (inset). A composite paste of W in Candelilla wax serves as an electrical interconnect. The entire system, excluding the contact pad, rests between two encapsulation layers of PLGA (~100 μm thick). (Right) All components of the device naturally bioresorb via hydrolysis and metabolic action in the body. PLGA degrades into its monomers, glycolic and lactic acid; the W/Mg electrode degrades into WOx and Mg(OH)2 respectively. The Si NM degrades into non-toxic Si(OH)4. Dissolution of Candelilla wax occurs by cleavage of the ester, anhydride, and moieties via hydrolysis. Panel b: Images of dissolution of a device associated with immersion in PBS (pH=7.4) at physiological temperature (37° C.). Scale bar, 10 mm. Panel c: Schematic illustration of the wireless and battery-free operation of an implanted device via inductive coupling between an external transmission coil (Tx) and the receiver (Rx) coil on the device. Panel d: Bioresorption thereby eliminates the device after a period of therapy to bypass the need for device removal.

#FIG. 2 shows ex vivo demonstrations of bioresorbable cardiac pacemakers on mouse and rabbit hearts, and human cardiac tissue, according to embodiments of the invention. Panels a, d, g: Images of bioresorbable cardiac pacemakers on mouse (panel a) and rabbit (panel d) hearts and a human ventricular cardiac tissue slice (panel g). Positioning of the electrode of the bioresorbable pacemaker on the anterior ventricular myocardium (panels a, d) and the surface of the human ventricular cardiac tissue slice (panel g). Scale bar, 10 mm. Panels b, e, h: Far-field ECG recordings (panels b, e) and optical action potential maps (panel h) before (white background) and during (yellow background; red arrows indicate delivered electrical stimuli) electrical stimulation using bioresorbable devices. Panels c, f, i: Activation map of membrane potential for mouse, rabbit, and human myocardium show activation originating from the location of the electrode pad of the device as indicated by the white arrow. Scale bar, 5 mm.

#The invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like reference numerals refer to like elements throughout.

#The terms used in this specification generally have their ordinary meanings in the art, within the context of the invention, and in the specific context where each term is used. Certain terms that are used to describe the invention are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner regarding the description of the invention. For convenience, certain terms may be highlighted, for example using italics and/or quotation marks. The use of highlighting has no influence on the scope and meaning of a term; the scope and meaning of a term is the same, in the same context, whether or not it is highlighted. It will be appreciated that same thing can be said in more than one way. Consequently, alternative language and synonyms may be used for any one or more of the terms discussed herein, nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein. Synonyms for certain terms are provided. A recital of one or more synonyms does not exclude the use of other synonyms. The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to various embodiments given in this specification.

#One of ordinary skill in the art will appreciate that starting materials, biological materials, reagents, synthetic methods, purification methods, analytical methods, assay methods, and biological methods other than those specifically exemplified can be employed in the practice of the invention without resort to undue experimentation. All art-known functional equivalents, of any such materials and methods are intended to be included in this invention. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.