Pericardial heart valve replacement and methods of constructing the same

• US 9,675,450 B2
• Filed: 08/17/2012
• Issued: 06/13/2017
• Est. Priority Date: 06/05/2012
• Status: Expired due to Fees

• Current Assignee: David Schornik, Frantisek Straka
• Original Assignee: David Schornik, Franisek Straka
• Inventors: Straka, Franti{hacek over (s)}ek, Ma{hacek over (s)}n, Jaroslav, Schornk, David, Pirk, Jan
• Primary Examiner(s): DUKERT, BRIAN AINSLEY
• Application Number:
  US14/406,024
• Publication Number:
  US 20150335422A1
• Time in Patent Office: 1,761 Days
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61F 2/2418 Scaffolds therefor, e.g. support stents
• CPC Class Codes: A61F 2/2472 Devices for testing
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2240/002 Designing or making customized prostheses
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062

Abstract

The pericardial heart valve replacement (1) is constructed from living tissue of autologous pericardium containing living pericardial interstitial cells (PICs) and a living extracellular matrix (ECM) in the following way: in the first step the size and shape of the patient'"'"'s native pathological heart valve is determined using real-time three-dimensional transesophageal echocardiography (TEE) or computer tomography (CT angiography) or magnetic resonance imaging (MRI); in the next step a stented (2) or a stentless pericardial heart valve replacement (1) is constructed from a single sheet of living autologous pericardium obtained from the patient; the size and shape of the pericardial heart valve replacement (1) corresponds to the size and shape of the patient'"'"'s native heart valve and aortic or pulmonary root. The subject matter of the invention also includes the development of a device (5) for the conditioning and modification of the living autologous pericardial heart valve replacement (1) consisting of a ipulsatile pump (6) driving the flow of culture medium in the device (5) to perfuse the cells in the pericardium, a reservoir (7) regulating the fluid capacitance and function of the pericardial heart valve replacement (1), a chamber (8) containing a holder (9) for the placement of the pericardial heart valve replacement (1) during dynamic conditioning, and a gas exchanger (10a, b) for perfusing CO₂ into the culture medium. The reservoir (7), the chamber (8) and the gas exchanger (10a, b) are placed in an incubator (11) with an inner atmosphere of air mixed with 5% CO₂ and a temperature of 36 to 37° C., the individual components of the device (5) being connected by tubing (12).

Claims

1. A method of constructing a pericardial heart valve replacement made from tissue of living autologous pericardium comprising:

determining the size and shape of the patient'"'"'s native pathological heart valve by real-time three-dimensional transesophageal echocardiography (TEE) or computer tomography (CT angiography) or by magnetic resonance imaging (MRI);

constructing a living pericardial heart valve replacement for stented or stentless implantation from a single sheet of dynamically conditioned living autologous pericardium containing living pericardial interstitial cells (PICs) and a living extracellular matrix (ECM);

tailoring the size and shape of the heart valve replacement so as to match the size and shape of the patient'"'"'s native heart valve and aortic root; and

dynamic conditioning and hemodynamic testing for conditioning and modification of the living autologous pericardium a device for a period of approximately 7 to 21 days in a device, the device comprising a hydrodynamic circuit of an artificial heart whereby hemodynamic loading of the living pericardial heart valve replacement induces pericardial interstitial cell (PIC) activation and phenotypic differentiation resulting in the production and remodeling of pericardial extracellular matrix (ECM) with an increase in the content of collagen and elastic fibers and glycosaminoglycans, thereby improving the mechanobiological and hemodynamic properties of the living pericardial heart valve replacement.

2. The method according to claim 1, further comprising for a stentless living pericardial heart valve replacement:

preparing a temporary anatomically tailored holding system to model the shape of the living pericardial heart valve replacement comprising a holder with profiled posts or a temporary stent; and

securing the living autologous pericardial tissue to the holding system by sutures through apertures in the holder, whereby the living pericardial heart valve replacement is removed from the holding system after completion of conditioning.

3. The method according to claim 1, wherein the device for conditioning and modification of the living autologous pericardial heart valve replacement creates a physiological environment for the dynamic loading of the living autologous pericardium at systolic and diastolic pressures of 110-140/70-80 mmHg and flow rate of culture medium around 5-6 l/min.

4. The method according to claim 1, wherein during the dynamic conditioning, the hemodynamic properties of the living pericardial heart valve replacement are measured including the transvalvular pressure gradients and the coaptation of valve cusps of the living pericardial heart valve replacement using echocardiography or flow rate and pressure sensors.

5. The method according to claim 1, wherein autologous circulating endothelial progenitor cells and circulating endothelial cells are used for endothelialization of the surface of the living pericardial heart valve replacement, these cells being isolated from the patient'"'"'s blood by immunomagnetic separation methods or by flow cytometry and multiplied in vitro, or autologous endothelial cells are used for endothelialization of the surface of the living pericardial heart valve replacement, these cells being harvested from the patient'"'"'s native heart valve using catheter endothelial biopsy of the surface of the native heart valve or endocardium and multiplied in vitro.

6. The method according to claim 1, wherein endothelialization is carried out in vitro in a static culture or in the device for conditioning and modification of the living autologous pericardium.

7. The method according to claim 1, wherein during dynamic conditioning and/or hemodynamic testing of the living pericardial heart valve replacement at least one of stem cells, endothelial progenitor cells, isolated pericardial interstitial cells, valve interstitial cells, blood products, growth factors, anticalciftcation agents, crosslinking agents, antibiotics, cytokines, immunomodulators, or nutrients is added to a culture medium.