Patent Publication Number: US-2021169644-A1

Title: Adaptable Prosthetic Tissue Valves

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part of U.S. application Ser. No. 16/440,504, filed on Jun. 13, 2019, which is a continuation-in-part of U.S. application Ser. No. 16/129,968, filed on Sep. 13, 2018, which is a continuation-in-part of U.S. application Ser. No. 15/206,833, filed on Jul. 11, 2016, now U.S. Pat. No. 10,188,510, which is a continuation-in-part application of U.S. application Ser. No. 14/960,354, filed on Dec. 5, 2015, now U.S. Pat. No. 9,907,649, which is a continuation-in-part application of U.S. application Ser. No. 14/229,854, filed on Mar. 29, 2014, now U.S. Pat. No. 9,308,084, which claims priority to U.S. Provisional Application No. 61/819,232, filed on May 3, 2013. 
    
    
     FIELD OF THE INVENTION 
     The present invention generally relates to prosthetic valves for replacing defective cardiovascular valves. More particularly, the present invention relates to prosthetic atrioventricular valves and methods for anchoring same to cardiovascular structures and/or tissue. 
     BACKGROUND OF THE INVENTION 
     As is well known in the art, the human heart has four valves that control blood flow circulating through the human body. Referring to  FIGS. 1A and 1B , on the left side of the heart  100  is the mitral valve  102 , located between the left atrium  104  and the left ventricle  106 , and the aortic valve  108 , located between the left ventricle  106  and the aorta  110 . Both of these valves direct oxygenated blood from the lungs into the aorta  110  for distribution through the body. 
     The tricuspid valve  112 , located between the right atrium  114  and the right ventricle  116 , and the pulmonary valve  118 , located between the right ventricle  116  and the pulmonary artery  120 , however, are situated on the right side of the heart  100  and direct deoxygenated blood from the body to the lungs. 
     Referring now to  FIGS. 1C and 1D , there are also generally five papillary muscles in the heart  100 ; three in the right ventricle  116  and two in the left ventricle  106 . The anterior, posterior and septal papillary muscles  117   a ,  117   b ,  117   c  of the right ventricle  116  each attach via chordae tendineae  113   a ,  113   b ,  113   c  to the tricuspid valve  112 . The anterior and posterior papillary muscles  119   a ,  119   b  of the left ventricle  106  attach via chordae tendineae  103   a ,  103   b  to the mitral valve  102  (see also  FIG. 1E ). 
     Since heart valves are passive structures that simply open and close in response to differential pressures, the issues that can develop with valves are typically classified into two categories: (i) stenosis, in which a valve does not open properly, and (ii) insufficiency (also called regurgitation), in which a valve does not close properly. 
     Stenosis and insufficiency can occur as a result of several abnormalities, including damage or severance of one or more chordae or several disease states. Stenosis and insufficiency can also occur concomitantly in the same valve or in different valves. 
     Both of the noted valve abnormalities can adversely affect organ function and result in heart failure. By way of example, referring first to  FIG. 1E , there is shown normal blood flow (denoted “BF N ”) proximate the mitral valve  102  during closure. Referring now to  FIG. 1F , there is shown abnormal blood flow (denoted “BF A ”) or regurgitation caused by a prolapsed mitral valve  102   p . As illustrated in  FIG. 1F , the regurgitated blood “BF A ” flows back into the left atrium, which can, if severe, result in heart failure. 
     In addition to stenosis and insufficiency of a heart valve, surgical intervention may also be required for certain types of bacterial or fungal infections, wherein the valve may continue to function normally, but nevertheless harbors an overgrowth of bacteria (i.e. “vegetation”) on the valve leaflets. The vegetation can, and in many instances will, flake off (i.e. “embolize”) and lodge downstream in a vital artery. 
     If such vegetation is present on the valves of the left side (i.e., the systemic circulation side) of the heart, embolization can, and often will, result in sudden loss of the blood supply to the affected body organ and immediate malfunction of that organ. The organ most commonly affected by such embolization is the brain, in which case the patient can, and in many instances will, suffer a stroke. 
     Likewise, bacterial or fungal vegetation on the tricuspid valve can embolize and affect the lungs. The noted embolization can, and in many instances will, result in lung dysfunction. 
     Treatment of the noted heart valve dysfunctions often requires replacement of the diseased or defective heart valve with a prosthetic heart valve. 
     Various prosthetic heart valves have thus been developed for replacement of natural diseased or defective heart valves. Illustrative are the tubular prosthetic mammalian tissue valves disclosed in Applicant&#39;s U.S. Pat. Nos. 9,044,319, 8,845,719, 8,709,076, 8,790,397, 8,696,744, 8,409,275 and 9,011,526. Further tubular prosthetic valves are disclosed in U.S. Pat. Nos. 8,257,434 and 7,998,196. 
     A problem that is often encountered with replacing diseased or defective native heart valves with a prosthetic heart valve is obtaining a secure and reliable engagement of the prosthetic heart valves to cardiovascular structures; particularly, a valve annulus. 
     Various structures and means have thus been developed to provide secure and reliable attachment of remodelable prosthetic valves to a valve annulus. 
     The most common surgical method that is employed to engage a prosthetic heart valve to a valve annulus comprises suturing the annular engagement end, i.e., proximal end, of the prosthetic valve directly to the valve annulus. 
     As is well known in the art, there are, however, numerous drawbacks and disadvantages associated with the noted surgical method. A major drawback is the high risk of perivalvular leaks due to ineffective suturing techniques and sizing mis-matches between the annular engagement end of the prosthetic valve and the host valve annulus. 
     The further surgical method that is often employed to engage a prosthetic heart valve; particularly, a prosthetic heart valve comprising mammalian tissue, to a valve annulus comprises employing an annular ring, e.g., a circular synthetic ring, which, in some instances is disposed on the annular engagement end of the valve, such as described and illustrated in Applicant&#39;s U.S. Pat. No. 8,409,275, and suturing the annular engagement end of the valve and associated annular ring directly to the valve annulus. 
     Although it has been found that such method can, and in most instances will, substantially reduce the risk of perivalvular leaks, as discussed below, since the annular engagement end of the valve and associated annular ring typically comprise a fixed size, several additional issues are presented. 
     As is well known in the art, a valve annulus can, and many times will, fluctuate in size, e.g., dilated cardiomyopathy, mitral valve regurgitation and Ebstein anomaly. A valve annulus can also be abnormally large or small. 
     When a fixed annular engagement end of a prosthetic valve is secured to a valve annulus with an abnormal valve annulus size, the size of the annular engagement end is typically adjusted to match the abnormal valve annulus size and, thus, merely accommodates the pathology of the cardiovascular disease or disorder associated with the abnormal valve annulus size. 
     There are, thus, several significant drawbacks and disadvantages associated with adjusting a fixed annular engagement end of a prosthetic valve to match an abnormal valve annulus size. 
     A major disadvantage is that when a fixed annular engagement end of a prosthetic valve is sized to match a valve annulus having an abnormally large or small valve annulus size due to a cardiovascular disease or disorder, healing of the valve annulus tissue is often adversely affected. 
     Further, when the disease or disorder is addressed or managed, the valve annulus often returns to a normal physiologically functional size and the fixed annular engagement end will no longer be able to accommodate the valve annulus. This often necessitates an additional valve replacement procedure to replace the prosthetic valve with an appropriately sized valve. 
     A similar situation is presented when a prosthetic valve having a fixed annular engagement end is implanted in an infantile, juvenile or adolescent host. As the host ages and the valve annulus size increases, the fixed annular engagement end will no longer be able to accommodate the valve annulus and an additional valve replacement procedure will similarly be necessary to replace the prosthetic valve with an appropriately sized valve. 
     There is thus a need to provide prosthetic valves that are configured and adapted to: (i) accommodate a broad range of valve annulus configurations and dimensions, (ii) adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus in vivo, whereby, the annular engagement end or region of the valves maintains sealed engagement to the valve annulus, and (iii) significantly decrease or effectively eliminate the incidence of perivalvular leaks. 
     There is also a need for improved methods for attaching prosthetic valves to cardiovascular structures and/or tissue that significantly decrease or effectively eliminate the incidence of perivalvular leaks. 
     It is therefore object of the present invention to provide prosthetic valves having an adaptable or dynamic annular engagement end or region that will accommodate a broad range of valve annulus configurations and dimensions, and adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus in vivo, whereby, the annular engagement end or region of the valves maintains sealed engagement to the valve annulus. 
     It is another object of the present invention to provide improved prosthetic valves that significantly decrease or effectively eliminate the incidence of perivalvular leaks after implant in a subject. 
     It is another object of the present invention to provide improved methods for attaching prosthetic valves to cardiovascular structures and/or tissue that significantly decrease or effectively eliminate the incidence of perivalvular leaks. 
     It is another object of the present invention to provide improved prosthetic valves and methods for attaching same to cardiovascular structures and/or tissue that maintain or enhance the structural integrity of the valves when the valves are subjected to cardiac cycle induced stress. 
     It is another object of the present invention to provide improved prosthetic valves and methods for attaching same to cardiovascular structures and/or tissue that preserve the structural integrity of the cardiovascular structure(s) when attached thereto. 
     It is another object of the present invention to provide prosthetic valves that remodel, and induce host tissue proliferation, remodeling and regeneration of new tissue and tissue structures with site-specific structural and functional properties when engaged to cardiovascular structures. 
     It is another object of the present invention to provide prosthetic valves that induce adaptive regeneration when engaged to cardiovascular structures and subjected to cardiac cycle forces. 
     It is another object of the present invention to provide prosthetic valves that are capable of administering at least one biologically active agent and/or pharmacological agent to host tissue and, thereby produce a desired biological and/or therapeutic effect when disposed proximate the host tissue. 
     SUMMARY OF THE INVENTION 
     The present invention is directed to prosthetic valves that can be readily employed to selectively replace diseased or defective heart valves, and methods for attaching (or anchoring) same to cardiovascular structures and/or tissue. 
     In a preferred embodiment of the invention, the prosthetic valves comprise base valve structures or members, which are formed from a pre-formed sheet structure. 
     In a preferred embodiment of the invention, the base valve members comprise an annular engagement end, a closed distal end region that restricts fluid flow therethrough, and a plurality of elongated ribbon members. 
     In a preferred embodiment of the invention, the plurality of elongated ribbon members form a plurality of fluid flow modulating regions, which transition from an open fluid flow configuration to a closed fluid flow configuration in response to expansion and contraction of the base valve member. 
     In a preferred embodiment of the invention, the prosthetic valves further comprise an internal support structure that is configured and adapted to exert at least one, more preferably, a plurality of retaining forces, on the annular engagement ends of the base valve members and, hence, prosthetic valves formed therewith, whereby the support structure (i) conforms to the annular engagement end of the prosthetic valves, (ii) securely positions the annular engagement ends of the prosthetic valves adjacent to and, thereby, in contact with a target valve annulus, whereby the annular engagement ends of the prosthetic valves conform to the shape of the valve annulus, and (iii) the annular engagement ends of the prosthetic valves adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus, e.g., a mitral valve annulus, whereby the annular engagement ends of the prosthetic valves maintain contact therewith. 
     In some embodiments of the invention, when the support structure exerts a retaining force on the annular engagement ends of the prosthetic valves, the support structure is further adapted to maintain contact of the annular engagement ends of the prosthetic valves to the valve annulus for a predetermined period of time. 
     According to the invention, the base valve members and support structures can comprise various biocompatible materials. 
     In a preferred embodiment of the invention, the base valve members comprise mammalian-based tissue. 
     In a preferred embodiment, the mammalian-based tissue comprises acellular ECM and, hence, an ECM composition comprising same. 
     In some embodiments of the invention, the mammalian-based tissue (and, thereby, compositions comprising same) further comprises at least one additional biologically active agent or composition, i.e., an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue. 
     In some embodiments of the invention, the biologically active agent comprises a growth factor, including, without limitation, transforming growth factor beta (TGF-β), fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor (VEGF). 
     In some embodiments of the invention, the biologically active agent comprises an exosome. 
     In some embodiments of the invention, the mammalian-based tissue (and, thereby, compositions comprising same) further comprises at least one pharmacological agent or composition (or drug), i.e., an agent or composition that is capable of producing a desired biological effect in vivo, e.g., stimulation or suppression of apoptosis, stimulation or suppression of an immune response, etc. 
     In some embodiments of the invention, the pharmacological agent comprises a statin, i.e., a HMG-CoA reductase inhibitor, such as cerivastatin. 
     In some embodiments of the invention, the pharmacological agent comprises an antibiotic, such as vancomycin and gentamicin. 
     In some embodiments of the invention, the support structures similarly comprise an ECM composition comprising acellular ECM derived from mammalian tissue. 
     In some embodiments, the support structures comprise a polymeric composition comprising at least one biocompatible polymer. 
     In some embodiments, the support structures comprise a biocompatible metal, such as a nickel-titanium alloy and stainless steel. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Further features and advantages will become apparent from the following and more particular description of the preferred embodiments of the invention, as illustrated in the accompanying drawings, and in which like referenced characters generally refer to the same parts or elements throughout the views, and in which: 
         FIGS. 1A-1D  are schematic illustrations of a human heart; 
         FIG. 1E  is an illustration of a normal mitral valve; 
         FIG. 1F  is an illustration of a prolapsed mitral valve; 
         FIG. 2A  is a top plan view of one embodiment of a base “ribbon structure” valve member in a pre-formed configuration, in accordance with the invention; 
         FIG. 2B  is a perspective view of the base “ribbon structure” valve member shown in  FIG. 2A  in a further pre-formed configuration, in accordance with the invention; 
         FIG. 2C  is a perspective view of the base “ribbon structure” valve member shown in  FIGS. 2A and 2B  in a formed operational configuration, i.e., a formed prosthetic “ribbon structure” valve, in accordance with the invention; 
         FIG. 3A  is a top plan view of a further embodiment of a base “ribbon structure” valve member having one embodiment of an adaptive support structure associated therewith in a pre-formed configuration, in accordance with the invention; 
         FIG. 3B  is a perspective view of the base “ribbon structure” valve member shown in  FIG. 3A  in a formed operational configuration, i.e., a formed prosthetic “ribbon structure” valve having the embodiment of the adaptive support structure shown in  FIG. 3A  associated therewith, in accordance with the invention; 
         FIG. 3C  is a perspective partial sectional view of another embodiment of the prosthetic “ribbon structure” valve shown in  FIG. 3B  having a structural ring disposed at the distal end of the valve, in accordance with the invention; 
         FIG. 3D  is a perspective partial sectional view of another embodiment of the prosthetic “ribbon structure” valve shown in  FIG. 3B  having a further embodiment of an adaptive support structure associated therewith, in accordance with the invention; 
         FIG. 3E  is an end plane view of the annular engagement end of the prosthetic “ribbon structure” valve shown in  FIG. 3D , in accordance with the invention; 
         FIG. 3F  is a perspective partial sectional view of another embodiment of the prosthetic “ribbon structure” valve shown in  FIG. 3B  having supplemental support structures disposed between the annular engagement end and distal end of the valve, in accordance with the invention; 
         FIG. 3G  is a perspective partial sectional view of another embodiment of the prosthetic “ribbon structure” valve shown in  FIG. 3B  formed from multiple overlaid base “ribbon structure” valve members, i.e., a multi-sheet prosthetic “ribbon structure” valve having one embodiment of an adaptive support structure associated therewith, in accordance with the invention; 
         FIG. 3H  is a perspective partial sectional view of another embodiment of the multi-sheet prosthetic “ribbon structure” valve shown in  FIG. 3G  having a further embodiment of an adaptive support structure associated therewith, in accordance with the invention; 
         FIG. 4A  is a top plan view of one embodiment of a multi-sheet base “ribbon structure” member having one embodiment of an adaptive support structure associated therewith in a pre-formed configuration, in accordance with the invention; 
         FIG. 4B  is a perspective view of the multi-sheet base “ribbon structure” valve member shown in  FIG. 4A  in a formed operational configuration, i.e., a formed prosthetic “ribbon structure” valve having the adaptive support structure shown in  FIG. 4A  associated therewith, in accordance with the invention, in accordance with the invention; 
         FIG. 5A  is perspective view of another embodiment of an adaptive support structure, in accordance with the invention; 
         FIG. 5B  is an end plane view of the adaptive support structure shown in  FIG. 5A , in accordance with the invention; 
         FIG. 5C  is a side plan view of one embodiment of a proximal end of an adaptive support structure member, in accordance with the invention; 
         FIG. 5D  is a side plan view of another embodiment of a proximal end of an adaptive support structure member, in accordance with the invention; 
         FIGS. 6A-6E  are perspective views of further embodiments of adaptive support structures, in accordance with the invention; 
         FIG. 7A  is a perspective view of a further embodiment of an adaptive support structure, in accordance with the invention; 
         FIG. 7B  is a side plan view of one embodiment of a prosthetic “ribbon structure” valve employing the adaptive support structure shown in  FIG. 7A , in accordance with the invention; 
         FIG. 8A  is a perspective view of one embodiment of an expandable annular ring support member in a pre-deployment configuration, in accordance with the invention; 
         FIG. 8B  is a perspective view of the expandable annular ring support member shown in  FIG. 8A  in an expanded post-deployment configuration, in accordance with the invention; 
         FIG. 9A  is an illustration of the prosthetic valve shown in  FIG. 3B  secured to an expanded (or abnormally large) mitral valve annulus region, in accordance with the invention; and 
         FIG. 9B  is an illustration of the prosthetic valve shown in  FIG. 3B  secured to a normal mitral valve annulus region, in accordance with the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Before describing the present invention in detail, it is to be understood that this invention is not limited to particularly exemplified apparatus, systems, structures or methods as such may, of course, vary. Thus, although a number of apparatus, systems and methods similar or equivalent to those described herein can be used in the practice of the present invention, the preferred apparatus, systems, structures and methods are described herein. 
     It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only and is not intended to be limiting. 
     Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one having ordinary skill in the art to which the invention pertains. 
     Further, all publications, patents and patent applications cited herein are hereby incorporated by reference herein in their entirety. 
     As used in this specification and the appended claims, the singular forms “a, “an” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to “a pharmacological agent” includes two or more such agents and the like. 
     Further, ranges can be expressed herein as from “about” or “approximately” one particular value, and/or to “about” or “approximately” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about” or “approximately”, it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. 
     It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” or “approximately” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “approximately 10” is also disclosed. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “10” is disclosed then “less than or equal to 10” as well as “greater than or equal to 10” is also disclosed. 
     Definitions 
     The terms “extracellular matrix”, “ECM”, and “ECM material” are used interchangeably herein, and mean and include a collagen-rich substance that is found in between cells in mammalian tissue, and any material processed therefrom, e.g., decellularized ECM. 
     The term “acellular ECM”, as used herein, means ECM that has a reduced content of cells. 
     According to the invention, ECM can be derived from a variety of mammalian tissue sources and tissue derived therefrom, including, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e., mesothelial tissue, dermal tissue, subcutaneous tissue, gastrointestinal tissue, tissue surrounding growing bone, placental tissue, omentum tissue, cardiac tissue, kidney tissue, pancreas tissue, lung tissue, and combinations thereof. The ECM can also comprise collagen from mammalian sources. 
     The terms “heart tissue” and “cardiac tissue” are used collectively herein, and mean and include, without limitation, mammalian tissue derived from any cardiovascular structure including, without limitation, pericardial tissue, myocardial tissue, vascular tissue and the like. 
     The terms “valve annulus” and “valve annulus region” are used collectively herein, and mean and include, without limitation, any physiological structure or region of a living organism that supports a native heart valve or a component thereof. 
     The terms “mammalian-based tissue”, “collagenous mammalian tissue” and “collagenous tissue” are used collectively herein, and mean and include, without limitation, tissue and compositions comprising same that is derived from a mammalian tissue source. 
     According to the invention, the collagenous mammalian tissue can similarly be derived from a variety of mammalian tissue sources and tissue derived therefrom, including, without limitation, the heart, small intestine, large intestine, stomach, lung, liver, kidney, pancreas, peritoneum, placenta, amniotic membrane, umbilical cord, bladder, prostate, and any fetal tissue from any mammalian organ. 
     The collagenous mammalian tissue can also be derived from a mammalian tissue source that is devoid of xenogeneic antigens, including, without limitation, collagenous mammalian tissue that is devoid of one of the following xenogeneic antigens: galactose-alpha-1,3-galactose (also referred to as α-gal), beta-1,4 N-acetylgalactosaminyltransferase 2, membrane cofactor protein, hepatic lectin H1, cytidine monophospho-N-acetylneuraminic acid hydroxylase, swine leukocyte antigen class I and porcine endogenous retrovirus polymerase (referred to herein as “immune privileged collagenous mammalian tissue”). 
     The term “genetically modified organism”, as used herein means and includes any living organism that has at least one gene modified by artificial means, e.g., gene editing. 
     The term “immune privileged collagenous mammalian tissue”, as used herein means and includes xenogeneic collagenous mammalian tissue that can be disposed proximate mammalian tissue with a minimal or virtually absent adverse immune response; particularly, an adverse immune response associated with xenogeneic tissue graft rejection. 
     According to the invention, the term “mammalian” means and includes, without limitation, wain blooded mammals, humans and primates; avians; domestic household or farm animals, such as cats, dogs, sheep, goats, cattle, horses and pigs; laboratory animals, such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like. 
     The term “crosslinked collagenous mammalian tissue”, as used herein, means and includes mammalian tissue that exhibits at least 25% chemical bonding of adjacent chains of molecules, i.e., collagen fibrils, which comprise the collagenous mammalian tissue. 
     The term “polymer”, as used herein means and includes, without limitation, polyurethane urea, porous polyurethane urea (Artelon®), polypropylene, poly(s-caprolactone) (PCL), poly(glycerol sebacate) (PGS), polytetrafluoroethylene (PTFE), poly(styrene-block-isobutylene-block-Styrene) (SIBS), polyglycolide (PGA), polylactide (PLA), polydioxanone (a polyether-ester), polylactide-co-glycolide, polyamide esters, polyalkalene esters, polyvinyl esters, polyvinyl alcohol, polyanhydrides, polyurethanes, polydimethylsiloxanes, poly(ethylene glycol), polytetrafluoroethylene (Teflon™) and polyethylene terephthalate (Dacron™), and combinations thereof. 
     The term “natural polymer”, as used herein means and includes, without limitation, polysaccharides (e.g., starch and cellulose), proteins (e.g., gelatin, casein, silk, wool, etc.), and polyesters (e.g., polyhydroxyalkanoates). 
     The term “biologically active agent”, as used herein, means and includes an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue. 
     The term “biologically active agent” thus means and includes a growth factor, including, without limitation, fibroblast growth factor-2 (FGF-2), transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF). 
     The term “biologically active agent” also means and includes a cell, including, without limitation, human embryonic stem cells, myofibroblasts, mesenchymal stem cells, and hematopoietic stem cells. 
     The term “biologically active agent” also means and includes an exosome and/or microsome. 
     The terms “exosome” and “microsome” as used herein mean and include a lipid bilayer structure that contains or encapsulates a biologically active agent and/or pharmacological agent, including, without limitation, a growth factor, e.g., TGF-β, TGF-α, VEGF and insulin-like growth factor (IGF-1), a cytokine, e.g., interleukin-10 (IL-10), a transcription factor and microRNA (miRNA). 
     The term “biologically active agent” also means and includes agents commonly referred to as a “protein”, “peptide” and “polypeptide”, including, without limitation, collagen (types I-V), proteoglycans and glycosaminoglycans (GAGs). 
     The terms “pharmacological agent”, “active agent” and “drug” are used interchangeably herein, and mean and include an agent, drug, compound, composition of matter or mixture thereof, including its formulation, which provides some therapeutic, often beneficial, effect. This includes any physiologically or pharmacologically active substance that produces a localized or systemic effect or effects in animals, including warm blooded mammals, humans and primates; avians; domestic household or farm animals, such as cats, dogs, sheep, goats, cattle, horses and pigs; laboratory animals, such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like. 
     The terms “pharmacological agent”, “active agent” and “drug” thus mean and include, without limitation, antibiotics, anti-arrhythmic agents, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal anti-inflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, growth factors, matrix metalloproteinases (MMPs), enzymes and enzyme inhibitors, anticoagulants and/or antithrombotic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents. 
     The terms “pharmacological agent”, “active agent” and “drug” also mean and include, without limitation, atropine, tropicamide, dexamethasone, dexamethasone phosphate, betamethasone, betamethasone phosphate, prednisolone, triamcinolone, triamcinolone acetonide, fluocinolone acetonide, anecortave acetate, budesonide, cyclosporine, FK-506, rapamycin, ruboxistaurin, midostaurin, flurbiprofen, suprofen, ketoprofen, diclofenac, ketorolac, nepafenac, lidocaine, neomycin, polymyxin b, bacitracin, gramicidin, gentamicin, oyxtetracycline, ciprofloxacin, ofloxacin, tobramycin, amikacin, vancomycin, cefazolin, ticarcillin, chloramphenicol, miconazole, itraconazole, trifluridine, vidarabine, ganciclovir, acyclovir, cidofovir, ara-amp, foscarnet, idoxuridine, adefovir dipivoxil, methotrexate, carboplatin, phenylephrine, epinephrine, dipivefrin, timolol, 6-hydroxydopamine, betaxolol, pilocarpine, carbachol, physostigmine, demecarium, dorzolamide, brinzolamide, latanoprost, sodium hyaluronate, insulin, verteporfin, pegaptanib, ranibizumab, and other antibodies, antineoplastics, anti-VEGFs, ciliary neurotrophic factor, brain-derived neurotrophic factor, bFGF, Caspase-1 inhibitors, Caspase-3 inhibitors, α-Adrenoceptors agonists, NMDA antagonists, Glial cell line-derived neurotrophic factors (GDNF), pigment epithelium-derived factor (PEDF), NT-3, NT-4, NGF and IGF-2. 
     The terms “pharmacological agent”, “active agent” and “drug” also mean and include the Class I-Class V antiarrhythnic agents disclosed in Applicant&#39;s U.S. Pat. Nos. 9,119,841, 10,188,509, 10,188,510 and 10,143,778, and Co-pending application Ser. Nos. 16/129,968 and 16/990,236, including, without limitation, (Class Ia) quinidine, procainamide and disopyramide; (Class Ib) lidocaine, phenytoin and mexiletine; (Class Ic) flecainide, propafenone and moricizine; (Class II) propranolol, esmolol, timolol, metoprolol and atenolol; (Class III) amiodarone, sotalol, ibutilide and dofetilide; (Class IV) verapamil and diltiazem) and (Class V) adenosine and digoxin. 
     The terms “pharmacological agent”, “active agent” and “drug” also mean and include, without limitation, the antibiotics disclosed in Applicant&#39;s U.S. Pat. Nos. 9,119,841, 10,188,509, 10,188,510 and 10,143,778, and Co-pending application Ser. Nos. 16/129,968 and 16/990,236, including, without limitation, aminoglycosides, cephalosporins, chloramphenicol, clindamycin, erythromycins, fluoroquinolones, macrolides, azolides, metronidazole, penicillin, tetracyclines, trimethoprim-sulfamethoxazole, gentamicin and vancomycin. 
     As indicated above, the terms “pharmacological agent”, “active agent” and “drug” also mean and include an anti-inflammatory. 
     The terms “anti-inflammatory” and “anti-inflammatory agent” are also used interchangeably herein, and mean and include a “pharmacological agent” and/or “active agent formulation”, which, when a therapeutically effective amount is administered to a subject, prevents or treats bodily tissue inflammation i.e., the protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissues. 
     The terms “anti-inflammatory” and “anti-inflammatory agent” thus include the anti-inflammatories disclosed in Applicant&#39;s U.S. Pat. Nos. 9,119,841, 10,188,509, 10,188,510 and 10,143,778, and Co-pending application Ser. Nos. 16/129,968 and 16/990,236, including, without limitation, desoximetasone, dexamethasone dipropionate, cloticasone propionate, diftalone, fluorometholone acetate, fluquazone, meseclazone, mesterolone, methandrostenolone, methenolone, methenolone acetate, methylprednisolone suleptanate, halopredone acetate, alclometasone dipropionate, apazone, balsalazide disodium, cintazone cormethasone acetate, cortodoxone, diflorasone diacetate, diflumidone sodium, endrysone, fenpipalone, flazalone, fluretofen, fluticasone propionate, isoflupredone acetate, nabumetone, nandrolone, nimazone, oxyphenbutazone, oxymetholone, phenbutazone, pirfenidone, prifelone, proquazone, rimexolone, seclazone, tebufelone and testosterone. 
     The terms “pharmacological agent”, “active agent” and “drug” also mean and include the statins, i.e., HMG-CoA reductase inhibitors, disclosed in Applicant&#39;s U.S. Pat. Nos. 9,119,841, 10,188,509, 10,188,510 and 10,143,778, and Co-pending application Ser. Nos. 16/129,968 and 16/990,236, including, without limitation, atorvastatin, cerivastatin, fluvastatin and lovastatin. 
     The terms “pharmacological agent”, “active agent”, “drug” and “active agent formulation” further mean and include the anti-proliferative agents disclosed in Applicant&#39;s U.S. Pat. Nos. 9,119,841, 10,188,509, 10,188,510 and 10,143,778, and Co-pending application Ser. Nos. 16/129,968 and 16/990,236, including, without limitation, paclitaxel, sirolimus and derivatives thereof, including everolimus. 
     The term “pharmacological composition”, as used herein, means and includes a composition comprising a “pharmacological agent” and/or any additional agent or component identified herein. 
     Additional biologically active and pharmacological agents are set forth in priority U.S. application Ser. No. 15/206,833, now U.S. Pat. No. 10,188,510, which is expressly incorporated herein in its entirety. 
     The term “therapeutically effective”, as used herein, means that the amount of the “pharmacological agent” and/or “biologically active agent” and/or “pharmacological composition” and/or “biologically active composition” administered is of sufficient quantity to ameliorate one or more causes, symptoms, or sequelae of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination, of the cause, symptom, or sequelae of a disease or disorder. 
     The terms “patient” and “subject” are used interchangeably herein, and mean and include warm blooded mammals, humans and primates; avians; domestic household or farm animals, such as cats, dogs, sheep, goats, cattle, horses and pigs; laboratory animals, such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like. 
     The term “comprise” and variations of the term, such as “comprising” and “comprises,” means “including, but not limited to” and is not intended to exclude, for example, other additives, components, integers or steps. 
     The term “comprise” and variations of the term, such as “comprising” and “comprises,” as used in connection with the a prosthetic valve composition and/or mammalian tissue, also means a composition and/or mammalian tissue employed to form a prosthetic valve structure, such as a sheet member, and, hence, a prosthetic valve of the invention. 
     The following disclosure is provided to further explain in an enabling fashion the best modes of performing one or more embodiments of the present invention. The disclosure is further offered to enhance an understanding and appreciation for the inventive principles and advantages thereof, rather than to limit in any manner the invention. The invention is defined solely by the appended claims including any amendments made during the pendency of this application and all equivalents of those claims as issued. 
     As stated above, the present invention is directed to prosthetic valves that can be readily employed to selectively replace diseased or defective heart valves, and methods for attaching (or anchoring) same to cardiovascular structures and/or tissue. 
     As discussed in detail below, in a preferred embodiment of the invention, the prosthetic valves comprise base valve structures or members, which are formed from pre-formed sheet structures. 
     In a preferred embodiment of the invention, the base valve members comprise seamless base valve members. 
     In a preferred embodiment of the invention, the base valve members further comprise an annular engagement end, a closed distal end region that restricts fluid flow therethrough, and a plurality of elongated ribbon members (referred to hereinafter as “base ‘ribbon structure’ valve members”). 
     In a preferred embodiment of the invention, the plurality of elongated ribbon members form a plurality of fluid flow modulating regions, which transition from an open fluid flow configuration to a closed fluid flow configuration in response to expansion and contraction of the base valve member. 
     As indicated above and discussed in detail below, in a preferred embodiment of the invention, the prosthetic valves further comprise a support structure that is configured and adapted to exert at least one, more preferably, a plurality of retaining forces, on the annular engagement ends of the base valve members and, hence, prosthetic valves formed therewith, whereby the support structure (i) conforms to the annular engagement end of the prosthetic valves, (ii) securely positions the annular engagement ends of the prosthetic valves adjacent to and, thereby, in contact with a target valve annulus valve, whereby the annular engagement ends of the prosthetic valves conform to the shape of the valve annulus, and (iii) the annular engagement ends of the prosthetic valves adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus, e.g., a mitral valve annulus, whereby the annular engagement ends of the prosthetic valves maintain contact therewith. 
     In some embodiments of the invention, when the support structure exerts a retaining force on the annular engagement ends of the prosthetic valves, the support structure is further adapted to maintain contact of the annular engagement ends of the prosthetic valves to the valve annulus for a predetermined period of time. 
     In some embodiments, the retaining force that is exerted by the support structure is in the range of approximately 0.2 to 0.5 lbs. 
     As discussed in detail below, in a preferred embodiment of the invention, the support structure comprises an adaptive support structure. 
     In some embodiments of the invention, the support structure comprises an annular ring that is disposed proximate the annular engagement end of the prosthetic valves. 
     In some embodiments of the invention, the annular ring comprises a microneedle anchoring mechanism that is further configured and adapted to engage the annular engagement end of the prosthetic valves, protrude through the annular engagement end of the prosthetic valves, engage cardiovascular tissue of a valve annulus (or other cardiovascular structure) and, thereby, position the prosthetic valve proximate the valve annulus. 
     Suitable anchoring mechanisms are disclosed in Applicant&#39;s U.S. Pat. Nos. 9,044,319, 10,188,509, 10,188,510 and 10,052,409, and U.S. application Ser. Nos. 16/193,669, 16/238,730 and 16/553,570, which are incorporated by reference herein in their entirety. 
     In some embodiments of the invention, the closed distal end region of the prosthetic valves comprises a structural ring that preferably enhances the structural integrity of the closed distal end region. 
     According to the invention, the prosthetic valves of the invention can further comprise a supplemental support structure, such as also disclosed in Applicant&#39;s U.S. Pat. Nos. 10,188,510 and 10,052,409, and/or a stent structure, such as described in Applicant&#39;s U.S. Pat. No. 10,188,513, which are also incorporated by reference herein. 
     According to the invention, the base “ribbon structure” valve members and/or support structures and/or annular rings and/or structural rings and/or supplemental support structures of the invention can comprise various biocompatible materials and compositions formed therefrom. 
     In some embodiments of the invention, the base “ribbon structure” valve members comprise mammalian-based tissue. 
     As indicated above, in a preferred embodiment of the invention, the mammalian-based tissue comprises acellular ECM (and, hence, ECM compositions comprising same) derived from a mammalian tissue source. 
     According to the invention, the ECM can be derived from various mammalian tissue sources and methods for preparing same, such as disclosed in U.S. Pat. Nos. 7,550,004, 7,244,444, 6,379,710, 6,358,284, 6,206,931, 5,733,337 and 4,902,508; which are incorporated by reference herein in their entirety. 
     The mammalian tissue sources include, without limitation, the small intestine, large intestine, stomach, lung, liver, kidney, pancreas, peritoneum, placenta, heart, bladder, prostate, tissue surrounding growing enamel, tissue surrounding growing bone, and any fetal tissue from any mammalian organ. 
     The mammalian tissue sources can thus comprise, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e., mesothelial tissue, dermal tissue, subcutaneous tissue, gastrointestinal tissue, placental tissue, omentum tissue, cardiac tissue, kidney tissue, pancreas tissue, lung tissue, and combinations thereof. The ECM can also comprise collagen from mammalian sources. 
     According to the invention, the ECM can also be derived from the same or different mammalian tissue sources, as disclosed in U.S. application Ser. Nos. 13/033,053 and 13/033,102, now U.S. Pat. No. 8,758,448; which are incorporated by reference herein. 
     In a preferred embodiment of the invention, the ECM comprises sterilized and decellularized ECM. 
     According to the invention, the ECM can be sterilized and decellularized by various conventional means. 
     In some embodiments of the invention, the ECM is sterilized and decellularized via applicant&#39;s proprietary process disclosed in U.S. application Ser. No. 13/480,205 and U.S. Pat. Nos. 9,060,969 and 9,446,078; which are expressly incorporated by reference herein in their entirety. 
     It is thus contemplated that, following placement of a base “ribbon structure” valve member comprising an ECM composition, i.e., acellular ECM, (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) on or in a cardiovascular structure (or structures) of a subject, e.g., valve annulus, and, hence, proximate damaged cardiovascular tissue associated therewith, the base “ribbon structure” valve member will become populated with endogenous cells that will gradually remodel the base valve member, i.e., ECM tissue thereof, into cardiovascular tissue and tissue (and, hence, valve) structures. 
     It is further contemplated that, following placement of a base “ribbon structure” valve member comprising an ECM composition, i.e., acellular ECM, (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) on or in a cardiovascular structure (or structures) of a subject, and, hence, proximate damaged cardiovascular tissue associated therewith, stem cells will migrate to the base “ribbon structure” valve member, i.e., ECM tissue thereof, from the point(s) at which the base “ribbon structure” valve member is attached to the cardiovascular structure or structures. 
     It is still further contemplated that, during circulation of epithelial and endothelial progenitor cells after placement of a base “ribbon structure” valve member comprising an ECM composition comprising acellular ECM (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) on a cardiovascular structure (or structures), the surfaces of the base “ribbon structure” valve member, i.e., ECM tissue thereof, will rapidly become lined or covered with epithelial and/or endothelial progenitor cells. 
     It is still further contemplated that the points at which abase “ribbon structure” valve member comprising an ECM composition (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) is attached to a cardiovascular structure (or structures) in a subject will serve as points of constraint that direct remodeling of the ECM into cardiovascular tissue and valve structures that are identical or substantially identical to properly functioning native cardiovascular tissue and valve structures. 
     According to the invention, the mammalian-based tissue can further comprise collagenous mammalian tissue derived from a mammalian tissue source. 
     According to the invention, the collagenous mammalian tissue can be similarly be derived from a variety of mammalian tissue sources and tissue derived therefrom, including, without limitation, the heart, small intestine, large intestine, stomach, lung, liver, kidney, pancreas, peritoneum, placenta, amniotic membrane, umbilical cord, bladder, prostate, and any fetal tissue from any mammalian organ. 
     In some embodiments of the invention, the collagenous mammalian tissue comprises pericardium tissue. 
     In some embodiments of the invention, the mammalian tissue source comprises a bovine tissue source, e.g., bovine pericardium tissue. 
     In some embodiments of the invention, the mammalian tissue source comprises a porcine tissue source, e.g., porcine pericardium tissue. 
     In some embodiments, the collagenous mammalian tissue comprises crosslinked collagenous mammalian tissue. 
     In some embodiments of the invention, the collagenous mammalian tissue is derived from a mammalian tissue source that is devoid of xenogeneic antigens. 
     In some embodiments, the collagenous mammalian tissue thus comprises collagenous mammalian tissue that is devoid of one of the following xenogeneic antigens: galactose-alpha-1,3-galactose (also referred to as α-gal), beta-1,4 N-acetylgalactosaminyl-transferase  2 , membrane cofactor protein, hepatic lectin H1, cytidine monophospho-N-acetylneuraminic acid hydroxylase, swine leukocyte antigen class I and porcine endogenous retrovirus polymerase (referred to hereinafter as “immune privileged collagenous mammalian tissue”). 
     In some embodiments, the immune privileged collagenous mammalian tissue is derived from a genetically modified organism, such as, by way of example, a genetically modified pig and/or bovine. 
     In some embodiments, the immune privileged collagenous mammalian tissue is thus derived from a genetically modified pig. 
     In some embodiments, the genetically modified pig comprises a pig originating from at least one porcine germline cell, e.g., embryo, that has been genetically altered or reconstructed to knockout or delete at least one porcine gene that encodes for a xenogeneic antigen product. 
     According to the invention, the genetic alteration or reconstruction of a germline cell; more specifically, a porcine embryo can be done according to any conventional gene editing method, such as conventional gene editing methods that employ clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, Transcription Activator-like Effector Nucleases (TALEN) or RNA interference. 
     In some embodiments, the knockout or deletion of a gene in a porcine embryo and, hence, pig developed therefrom is done according to the CRISPR-Cas9 gene editing method described in Niu, et al.,  Inactivation of Porcine Endogenous Retrovirus in Pigs Using CRISPR - Cas 9, Science, vol. 357, no. 6357, pp. 1303-1307 (2017), which is incorporated by reference herein in its entirety. 
     According to the invention, the noted gene editing methods can be adapted and configured to knockout or delete any genes in a porcine embryo that encode for xenogeneic antigens including, without limitation, GGTA1 (galactose-alpha-1,3-galactose), β4GalNT2 (beta-1,4 N-acetylgalactosaminyltransferase 2), CD46 (membrane cofactor protein), ASGR1 (hepatic lectin H1), CMAH (cytidine monophospho-N-acetylneuraminic acid hydroxylase), SLA class I (swine leukocyte antigen class I) and PERV pol (porcine endogenous retrovirus polymerase) gene. 
     In some embodiments, the collagenous mammalian tissue is derived from mammalian tissue of a pig developed from an embryo that has been genetically altered by knocking out or deleting the genes GGTA1, β4GalNT2 and CMAH, which encode for the xenogeneic antigen products galactose-alpha-1,3-galactose, beta-1,4 N-acetylgalactosaminyltransferase 2 and cytidine monophospho-N-acetylneuraminic acid hydroxylase, respectively. 
     According to the invention, the likelihood of inducing an adverse immune response, including adverse immune responses associated with xenogeneic tissue graft rejection, in vivo with the above referenced immune privileged collagenous mammalian tissue is minimal. 
     In some embodiments of the invention, the prosthetic valves of the invention are formed from and, hence, comprise a polymeric composition comprising at least one polymer; preferably, a biocompatible polymer. 
     According to the invention, suitable biocompatible polymers include, without limitation, polyurethane urea, including porous polyurethane urea (Artelon®), polypropylene, poly(ε-caprolactone) (PCL), poly(glycerol sebacate) (PGS), polytetrafluoroethylene (PTFE), poly(styrene-block-isobutylene-block-Styrene) (SIBS), polyglycolide (PGA), polylactide (PLA), polydioxanone (a polyether-ester), polylactide-co-glycolide, polyamide esters, polyalkalene esters, polyvinyl esters, polyvinyl alcohol, polyanhydrides, polyurethanes, polydimethylsiloxanes, poly(ethylene glycol), polytetrafluoroethylene (Teflon™), and polyethylene terephthalate (Dacron™), and combinations thereof. 
     In some embodiments of the invention, the mammalian-based tissue (and compositions comprising same) and/or polymeric composition further comprises at least one additional biologically active agent or composition, i.e., an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue. 
     According to the invention, suitable biologically active agents include any of the aforementioned biologically active agents, and agents set forth in Applicant&#39;s U.S. Pat. No. 10,188,510 and U.S. application Ser. No. 15/877,803, which are incorporated by reference herein. 
     As indicated above, in some embodiments of the invention, the biologically active agent comprises a growth factor, including, without limitation, transforming growth factor beta (TGF-β), fibroblast growth factor-2 (FGF-2) (also referred to as basic fibroblast growth factor (bFGF)), and vascular endothelial growth factor (VEGF). 
     In some embodiments of the invention, the mammalian-based tissue (and compositions comprising same) and/or polymeric composition further comprises at least one pharmacological agent or composition (or drug), i.e., an agent or composition that is capable of producing a desired biological effect in vivo, e.g., stimulation or suppression of apoptosis, stimulation or suppression of an immune response, etc. 
     According to the invention, suitable pharmacological agents and compositions include any of the aforementioned pharmacological agents and agents set forth in Applicant&#39;s U.S. Pat. No. 10,188,510 and U.S. application Ser. No. 15/877,803. 
     In some embodiments of the invention, it is thus contemplated that, following placement of a base “ribbon structure” valve member (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) on or in a cardiovascular structure (or structures) in a subject and, hence, proximate cardiovascular tissue associated therewith, the base “ribbon structure” valve member (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) will induce “modulated healing” of the cardiovascular structure(s) and cardiovascular tissue associated therewith. 
     The term “modulated healing”, as used herein, and variants of this language generally refer to the modulation (e.g., alteration, delay and retardation) of a process involving different cascades or sequences of naturally occurring tissue repair in response to localized tissue damage or injury, substantially reducing their inflammatory effect. 
     Modulated healing, as used herein, includes many different biologic processes, including epithelial growth, fibrin deposition, platelet activation and attachment, inhibition, proliferation and/or differentiation, connective fibrous tissue production and function, angiogenesis, and several stages of acute and/or chronic inflammation, and their interplay with each other. 
     For example, in some embodiments of the invention, a base “ribbon structure” valve member of the invention (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) is specifically formulated (or designed) to alter, delay, retard, reduce, and/or detain one or more of the phases associated with healing of damaged tissue, including, but not limited to, the inflammatory phase (e.g., platelet or fibrin deposition), and the proliferative phase when in contact with biological tissue. 
     In some embodiments, “modulated healing” means and includes the ability of a base “ribbon structure” valve member of the invention (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) to restrict the expression of inflammatory components. By way of example, according to the invention, when a base “ribbon structure” valve member of the invention comprises a statin augmented ECM composition, i.e., a composition comprising ECM and a statin, and the base “ribbon structure” valve member is positioned proximate damaged biological tissue, e.g., attached to a valve annulus, the base “ribbon structure” valve member will restrict expression of monocyte chemoattractant protein-1 (MCP-1) and chemokine (C—C) motif ligand 2 (CCR2). 
     In some embodiments of the invention, “modulated healing” means and includes the ability of a base “ribbon structure” valve member of the invention, such as, for example, a base “ribbon structure” valve member comprising an antibiotic augmented polymeric composition, to alter a substantial inflammatory phase (e.g., platelet or fibrin deposition) at the beginning of the tissue healing process. 
     As used herein, the phrase “alter a substantial inflammatory phase” refers to the ability of a base “ribbon structure” valve member of the invention (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) to substantially reduce the inflammatory response at a damaged tissue site, e.g., valve annulus, when in contact with tissue at the site. 
     In such an instance, a minor amount of inflammation may ensue in response to tissue injury, but this level of inflammation response, e.g., platelet and/or fibrin deposition, is substantially reduced when compared to inflammation that takes place in the absence of a prosthetic valve of the invention. 
     The term “modulated healing” also refers to the ability of a base “ribbon structure” valve member of the invention, particularly, a base “ribbon structure” valve member comprising an ECM composition, to induce host tissue proliferation, bioremodeling, including neovascularization, e.g., vasculogenesis, angiogenesis, and intussusception, and regeneration of new tissue and tissue structures with site-specific structural and functional properties, when disposed proximate damaged tissue of a cardiovascular structure, e.g., a valve annulus. 
     Thus, in some embodiments of the invention, the term “modulated healing” means and includes the ability of a base “ribbon structure” valve member of the invention (and, hence, a prosthetic “ribbon structure” valve of the invention formed therewith) to modulate inflammation and induce host tissue proliferation and remodeling, and regeneration of new tissue when disposed proximate damaged tissue. 
     In some embodiments of the invention, the biologically active agent specifically comprises an exosome. 
     As discussed in detail in Applicant&#39;s U.S. application Ser. No. 15/386,640, now U.S. Pat. No. 10,143,778, which is incorporated by reference herein, exosomes significantly enhance the modulated healing induced by the base “ribbon structure” valve members of the invention (and, hence, prosthetic “ribbon structure” valves of the invention formed therewith); particularly, base “ribbon structure” valve members comprising an ECM composition, through several properties/capabilities. 
     A first seminal property is the capacity of exosomes to generate and provide an exosome lipid bilayer that shields bioactive molecules, e.g., biologically active agents, from proteolytic agents, which can, and often will, degrade unshielded (or free) bioactive molecules and render the molecules non-functional in biological tissue environments. 
     Exosomes also facilitate and enhance direct interaction by and between bioactive molecules; particularly, biologically active agents and endogenous cells (and, hence, direct delivery of bioactive molecules to endogenous cells) in biological tissue, which enhances the bioactivity of the agents. 
     Thus, it is contemplated that, in some embodiments of the invention, following placement of a prosthetic “ribbon structure” valve of the invention; particularly, a prosthetic “ribbon structure” valve comprising a base “ribbon structure” valve member comprising exogenously added exosomes, on or in a cardiovascular structure (or structures) of a subject, e.g., valve annulus, and, hence, proximate damaged cardiovascular tissue associated therewith, the prosthetic “ribbon structure” valve will induce a multitude of significant biological processes in vivo, including significantly enhanced inflammation modulation of the cardiovascular tissue, and significantly induced neovascularization, stem cell proliferation, remodeling of the cardiovascular tissue, and regeneration of new tissue and tissue structures. 
     By way of example, when a base “ribbon structure” valve member comprises an exosome augmented ECM composition comprising encapsulated IL-8 and the base “ribbon structure” valve member and, hence, prosthetic “ribbon structure” valve formed therefrom, is disposed proximate damaged cardiovascular tissue, the prosthetic “ribbon structure” valve will modulate the transition of M1 type “acute inflammatory” macrophages to M2 type “wound healing” macrophages initiated by the acellular ECM. 
     Byway of further example, when abase “ribbon structure” valve member comprises an exosome augmented ECM composition comprising encapsulated miRNAs, and the base “ribbon structure” valve member and, hence, prosthetic “ribbon structure” valve formed therefrom, is disposed proximate damaged cardiovascular tissue, the prosthetic “ribbon structure” valve will induce enhanced stem cell proliferation via the delivery of exosome encapsulated miRNAs and transcription factors to the damaged cardiovascular tissue, which signals the endogenous stem cells to bind and/or attach to the acellular ECM and proliferate. 
     In some embodiments of the invention, the support structures and/or annular rings and/or structural rings and/or supplemental support structures comprise one of the aforementioned mammalian-based tissues and/or compositions comprising same. 
     In some embodiments of the invention, the support structures and/or annular rings and/or structural rings and/or supplemental support structures comprise one of the aforementioned biocompatible polymers and/or polymeric compositions comprising same. 
     According to the invention, the polymeric composition can further comprise a natural polymer, including, without limitation, polysaccharides (e.g., starch and cellulose), proteins (e.g., gelatin, casein, silk, wool, etc.), and polyesters (e.g., polyhydroxyalkanoates). 
     In some embodiments, the polymeric composition comprises a cross-linked ECM derived from any one of the aforementioned mammalian tissue sources. 
     In some embodiments, the polymeric composition comprises a glutaraldehyde cross-linked ECM. 
     According to the invention, the polymeric composition can further comprise a non-biodegradable polymer, including, without limitation, polytetrafluoroethylene (Teflon®) and polyethylene terephthalate (Dacron®). 
     In some embodiments, the polymeric composition comprises at least one of the aforementioned biologically active agents and/or pharmacologically active agents. 
     Thus, in some embodiments of the invention, the support structures and/or annular rings and/or structural rings and/or supplemental support structures similarly have the capacity to induce “modulated healing” of cardiovascular structures and tissue associated therewith. 
     In some embodiments of the invention, the support structures and/or annular rings and/or structural rings and/or supplemental support structures comprise a biocompatible metal. 
     According to the invention, suitable metals can comprise, without limitation, nickel-titanium alloy, such as Nitinol®, stainless steel and magnesium. 
     Referring now to  FIGS. 2A-2C , one embodiment of a base “ribbon structure” valve member of the invention, and method for forming same, will be described. 
     As indicated above, in a preferred embodiment of the invention, the base “ribbon structure” valve member comprises a plurality of elongated ribbon members, such as described in Applicant&#39;s Co-pending U.S. application Ser. No. 16/440,504, which is incorporated by reference herein. 
     A seminal feature of base “ribbon structure” valve members of the invention is that the base “ribbon structure” valve members are formed from and, hence, comprise a seamless pre-formed (or pre-cut) sheet structure. 
     As set forth in Applicant&#39;s Co-pending U.S. application Ser. No. 16/440,504, the base “ribbon structure” valve members can be formed from a single sheet member or multiple sheet members, such as base “ribbon structure” valve member  10   f  discussed below. 
     Referring now to  FIG. 2A , there is shown one embodiment of a pre-formed sheet member  80   a  that can be formed into seamless base “ribbon structure” valve members of the invention. 
     As illustrated in  FIG. 2A , the sheet member  80   a  comprises a central region  82  and a plurality of elongated ribbon members  60 , which extend from the central region  82 . According to the invention, the ribbon members  60  can comprise any length and shape. The ribbon members  60  can also comprise various widths proximate the proximal end  64 . 
     Referring now to  FIGS. 2B and 2C , the base “ribbon structure” valve member  10   a  is preferably formed by folding each of the elongated ribbon members  60  inwardly to form pre-formed valve structure  10   a ′ that is shown in  FIG. 2B , wherein the central region  82  of the sheet member  80   a  is disposed at the distal end  63  of base “ribbon structure” valve member  10   a ′ and forms a closed distal valve region  63 ′ that restricts fluid flow therethrough, and the first edge regions  61   a  and the second edge regions  61   b  of the ribbon members  60  are positioned adjacent each other and, as illustrated in  FIG. 2C , in the fully formed (or operational configuration) of base “ribbon structure” valve member  10   a , form a plurality of fluid flow modulating regions  69  having proximal and distal ends  68   a ,  68   b.    
     In a preferred embodiment, the length of each flow modulating region  69  is in the range of approximately 5-99% of the length of the base “ribbon structure” valve member  10   a , i.e., distance from the annular engagement end  65  to the distal end  63  of the base “ribbon structure” valve member  10   a . More preferably, the length of each flow modulating region  69  is in the range of approximately 10-90% of the length of the base “ribbon structure” valve member  10   a.    
     As further illustrated in  FIG. 2C , the proximal ends  64  of ribbon members  60  are also preferably positioned circumferentially about the annular engagement end  65  of the base “ribbon structure” valve member  10   a , wherein the base “ribbon structure” valve member  10   a , when fully formed operational configuration, comprises a substantially conical shaped base “ribbon structure” valve member. 
     As set forth in Applicant&#39;s Co-pending U.S. application Ser. No. 16/440,504, the base “ribbon structure” valve member  10   a  is configured to expand during fluid flow through the base “ribbon structure” valve member  10   a  that comprises a first fluid flow pressure, as shown in phantom in  FIG. 2C  (denoted  10   a ″), and contract when the fluid through the base “ribbon structure” valve member  10   a  comprises a second fluid flow pressure, the second fluid flow pressure being lower than the first fluid flow pressure. 
     As also set forth in Applicant&#39;s Co-pending U.S. application Ser. No. 16/440,504, the fluid flow modulating regions  69  are preferably configured to open during expansion of the base “ribbon structure” valve member  10   a , as shown in phantom in  FIG. 2C  and denoted  69 ′, i.e., the first and second edge regions  61   a ,  61   b  separate, wherein the fluid flow is allowed to be transmitted through the fluid flow modulating regions  69 , and close during the contraction of the base “ribbon structure” valve member  10   a , wherein the fluid flow through base “ribbon structure” valve member  10   a  is restricted. 
     According to the invention, the base “ribbon structure” valve member  10   a  can comprise any number of ribbon members  60 . As illustrated in  FIGS. 2A-2C , in some embodiments of the invention, the base “ribbon structure” valve member  10   a  has three (3) equally spaced ribbon members  60 . 
     Referring now to  FIGS. 3A-3H , several embodiments of prosthetic “ribbon structure” valves of the invention and methods for forming same will be described in detail. 
     Referring first to  FIG. 3B , there is shown one embodiment of a prosthetic “ribbon structure” valve of the invention, denoted  10   b . As illustrated in  FIG. 3B , the prosthetic “ribbon structure” valve  10   b  comprises conical shaped base “ribbon structure” valve member  10   a  and adaptive support structure  200 . 
     According to the invention, the prosthetic “ribbon structure” valve  10   b  is formed from a seamless pre-formed (or pre-cut) sheet member that is similar to sheet member  80   a  shown in  FIG. 2A . However, as illustrated in  FIG. 3A , in this instance, the pre-formed sheet member  80   b  now includes adaptive support structure  200 , which is operatively positioned thereon. 
     As further illustrated in  FIG. 3A , the sheet member  80   b  similarly comprises a central region  82  and a plurality of elongated ribbon members  60  having proximal and distal ends  64 ,  62 , which extend from the central region  82 . 
     According to the invention, the prosthetic “ribbon structure” valve  10   b  is similarly formed by folding each of the elongated ribbon members  60  of sheet member  80   b  and the elongated support members  202  of the adaptive support structure  200  associated therewith inwardly, wherein, as illustrated in  FIG. 3B , the central region  82  of the sheet member  80   a  is disposed proximate the distal end  63  of prosthetic valve  10   b  and forms a closed distal valve region  63 ′ that restricts fluid flow therethrough, and the first edge regions  61   a  and the second edge regions  61   b  of the ribbon members  60  are similarly positioned adjacent each other and form the plurality of fluid flow modulating regions  69 . 
     As further illustrated in  FIG. 3B , the adaptive support structure  200  preferably comprises a support structure base  210  and a plurality of elongated support members  202  having proximal and distal ends  206   a ,  206   b.    
     As also illustrated in  FIG. 3B , the proximal ends  206   a  of the elongated support members  202  are preferably positioned circumferentially about the annular engagement end  65  of the prosthetic “ribbon structure” valve  10   b.    
     As additionally illustrated in  FIG. 3B , the support structure base  210  is preferably disposed proximate the distal end  63  of prosthetic “ribbon structure” valve  10   b . The elongated support members  202  are also operatively connected to and extend outwardly from the support structure base  210 . 
     In a preferred embodiment, at least one elongated support member  202  extends outwardly along and is positioned substantially coincident with at least one elongated ribbon member  60 . More preferably, each of the elongated support members  202  are positioned substantially coincident with each of the elongated ribbon members  60 . 
     In some embodiments of the invention, at least one elongated support member  202  of the adaptive support structure  200  is operatively connected or engaged to a ribbon member  60 . 
     According to the invention, the elongated support members  202  of the adaptive support structure  200  can be operatively connected to the ribbon members  60  by various conventional means, including, without limitation, sutures, biocompatible adhesive compositions, etc. 
     According to the invention, the adaptive support structure  200  can comprise a biocompatible metal or any of the aforementioned mammalian-based tissues (and compositions comprising same) and polymeric compositions. 
     In some embodiments, the adaptive support structure  200  comprises a shape-memory alloy. 
     In a preferred embodiment of the invention, the shape-memory alloy comprises a nickel-titanium alloy. 
     In some embodiments, the nickel-titanium alloy comprises Nitinol®. 
     In some embodiments of the invention, the adaptive support structure  200  is configured to transition from a pre-deployment configuration, wherein the prosthetic “ribbon structure” valve associated therewith can be positioned proximate a valve annulus, to an expanded post-deployment configuration. 
     In such embodiments, when the adaptive support structure  200  transitions to the expanded post-deployment configuration, the adaptive support structure  200  conforms to the annular engagement ends of prosthetic “ribbon structure” valves associated therewith, e.g., annular engagement end  65  of prosthetic “ribbon structure” valve  10   b  and, in some embodiments, a valve annulus when the annular engagement ends of the prosthetic “ribbon structure” valves is in contact therewith. 
     According to the invention, transition of the adaptive support structure  200  from a pre-deployment configuration to a post-deployment configuration can be achieved or induced by various conventional means. 
     In some embodiments of the invention, transition of the adaptive support structure  200  from a pre-deployment configuration to a post-deployment configuration is achieved or induced by applying a radial force to the adaptive support structure  200  and/or an interior region of the prosthetic “ribbon structure” valve associated therewith, such as by a conventional balloon catheter device. 
     In some embodiments of the invention, transition of the adaptive support structure  200  from a pre-deployment configuration to a post-deployment configuration is achieved or induced by virtue of the adaptive support structure  200  composition, i.e., the adaptive support structure  200  comprises a shape-memory alloy, such as Nitinol®. 
     As indicated above, in a preferred embodiment of the invention, the adaptive support structure  200  is designed, configured and adapted to exert at least one, more preferably, a plurality of retaining forces, on the annular engagement end  65  of prosthetic “ribbon structure” valve  10   b  (and, hence, prosthetic valves  10   c ,  10   e ,  10   f  and  10   h , discussed below), whereby the support structure  200  ( i ) conforms to the annular engagement end  65  of prosthetic “ribbon structure” valve  10   b  (and, hence, prosthetic valves  10   c ,  10   e ,  10   f  and  10   h ), (ii) securely positions the annular engagement end  65  of the prosthetic valve  10   b  adjacent to and, thereby, in contact with a target valve annulus valve, whereby the annular engagement end  65  of prosthetic “ribbon structure” valve  10   b  conforms to the shape of the valve annulus, and (iii) the annular engagement end  65  of the prosthetic valve  10   b  and, thereby, prosthetic valve  10   b  adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus, whereby the annular engagement end  65  of the prosthetic valve  10   b  maintains contact therewith. 
     In some embodiments of the invention, when the adaptive support structure  200  exerts the retaining force(s) on the annular engagement end  65  of prosthetic “ribbon structure” valve  10   b  (and, hence, prosthetic valves  10   c ,  10   e ,  10   f  and  10   h ), the adaptive support structure  200  is further adapted to maintain contact of the annular engagement end  65  of the prosthetic valve  10   b  to the valve annulus for a predetermined period of time. 
     As indicated above, in a preferred embodiment of the invention, the support structure  200  (and support structures  250  and  300 , discussed herein) is further designed, configured and adapted to provide at least one outwardly directed retaining force to the annular engagement end  65  of prosthetic “ribbon structure” valve  10   b  and the annular engagement ends of the other prosthetic valves of the invention. 
     More preferably, the support structure  200  (and support structures  250  and  300 , discussed herein) is designed, configured and adapted to provide at least one outwardly directed force proximate the proximal end  206   a  of at least one of the elongated support members  202  (and proximate the proximal end  306   a  of support members  302 ) and, thereby, the proximal end  64  of at least one ribbon member  60 . 
     More preferably, the support structure  200  (and support structures  250  and  300 ) are designed, configured and adapted to provide a plurality of outwardly directed retaining forces proximate the proximal ends  206   a  of the elongated support members  202  (and proximate the proximal end  306   a  of support members  302 ) and, thereby the proximal ends  64  of the ribbon members  60 . 
     In some embodiments of the invention, the retaining force or forces provided by support structure  200  (and support structures  250  and  300 ) are preferably in the range of 0.2-0.5 lbs. 
     In some embodiments, the proximal ends  206   a  of the support members  202  comprise anchored ends that are adapted to engage, cardiovascular tissue and, thereby, position and secure the elongated support members  202  and, hence, prosthetic “ribbon structure” valve  10   a  associated therewith to a valve annulus and maintain engagement thereto for an enhanced support time period. 
     According to the invention, the anchored ends can comprise any suitable anchoring mechanism that is configured to engaged cardiovascular tissue and, thereby, position and secure a support member of the invention and, hence, a prosthetic valve associated therewith to a valve annulus. 
     In some embodiments, the anchored ends comprise barbed ends. In some embodiments, the anchored ends comprise deployable barbed ends, where the barbs are configured to transition from a recessed pre-deployment position to an extended post-deployment configuration. 
     Referring now to  FIG. 3C , there is shown another embodiment of the prosthetic “ribbon structure” valve  10   b  that is shown in  FIG. 3B . As illustrated in  FIG. 3C , the prosthetic “ribbon structure” valve, now denoted  10   c , includes a structural ring  40  that is disposed on the distal end  63  of the prosthetic valve  10   c.    
     According to the invention, the structural ring  40  can be disposed at any position on the closed distal valve region  63 ′ of prosthetic “ribbon structure” valve  10   c.    
     Referring now to  FIG. 3D , there is shown yet another embodiment of prosthetic “ribbon structure” valve  10   b  that is shown in  FIG. 3B , wherein the prosthetic valve, now denoted  10   d , includes another embodiment of an adaptive support structure of the invention, denoted  250 . 
     As illustrated in  FIGS. 3D and 3E , the adaptive support structure  250  includes an annular ring  225 , which is positioned proximate the proximal ends  206   a  of the adaptive support structure  250  elongated support members  202  and, hence, as illustrated in  FIG. 3D , proximate the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d.    
     According to the invention, the annular ring  225  can comprise an integral component or separate member. 
     In some embodiments of the invention, the annular ring  225  and, thereby, support structure  250 , is similarly configured to transition from a pre-deployment configuration, wherein a prosthetic “ribbon structure” valve associated therewith can be positioned proximate a valve annulus, to an expanded post-deployment configuration. 
     In such embodiments, when the annular ring  225  and, thereby, support structure  250 , transitions to the expanded post-deployment configuration, the annular ring  225  and, thereby, support structure  250 , conforms to the annular engagement ends of the prosthetic “ribbon structure” valves associated therewith and, in some embodiments, a valve annulus when the annular engagement end of the prosthetic “ribbon structure” valves is in contact therewith. 
     According to the invention, transition of the annular ring  225  and, thereby, support structure  250 , from a pre-deployment configuration to a post-deployment configuration can similarly be achieved or induced by various conventional means. 
     In some embodiments of the invention, transition of the annular ring  225  and, thereby, support structure  250 , from a pre-deployment configuration to a post-deployment configuration is achieved by applying a radial force to the annular ring  225  and/or an interior region of the prosthetic “ribbon structure” valve associated therewith, such as by a conventional balloon catheter device. 
     In some embodiments of the invention, transition of the annular ring  225  and, thereby, support structure  250 , from a pre-deployment configuration to a post-deployment configuration is achieved or induced by virtue of the adaptive support structure  250  composition, i.e., the annular ring  225  and/or adaptive support structure  250  comprises a shape-memory alloy, such as Nitinol®. 
     As indicated above, in a preferred embodiment of the invention, the annular ring  225  and, thereby, support structure  250 , are similarly designed, configured and adapted to exert at least one, more preferably, a plurality of retaining forces, on the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  (and, hence, prosthetic valve  10   g , discussed below), as shown in  FIG. 3E , whereby the annular ring  225  and, thereby, support structure  250  similarly (i) conform to the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  (and, hence, prosthetic valve  10   g ), (ii) securely position the annular engagement end  65  of the prosthetic “ribbon structure” valve  10   d  adjacent to and, thereby, in contact with a target valve annulus valve, whereby the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  and, thereby, prosthetic “ribbon structure” valve  10   d  conforms to the shape of the valve annulus, and (iii) the annular engagement end  65  of the prosthetic “ribbon structure” valve  10   d  adapts to at least one fluctuation in the configuration and/or dimension of the valve annulus, whereby the annular engagement end  65  of the prosthetic “ribbon structure” valve  10   d  maintains contact therewith. 
     In some embodiments of the invention, when the adaptive support structure  250  exerts the retaining force(s) on the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  (and, hence, prosthetic valve  10   g ), the adaptive support structure  250  is further adapted to maintain contact of the annular engagement end  65  of the prosthetic “ribbon structure” valve  10   d  to the valve annulus for a predetermined period of time. 
     As indicated above, in some embodiments of the invention, the annular ring  225  comprises a microneedle anchoring mechanism that is further configured and adapted to engage the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d , engage cardiovascular tissue of the valve annulus and, thereby, position the prosthetic valve  10   d  proximate the valve annulus. 
     According to the invention, the prosthetic “ribbon structure” valve  10   b  (and, hence, prosthetic valves  10   c ,  10   d ,  10   f ,  10   g ,  10   h  and  10   i ) can further comprise at least one supplemental support structure, such as described in Applicant&#39;s U.S. Pat. Nos. 10,188,509, 10,188,510 and 10,052,409, which are also incorporated by reference herein. 
     Referring now to  FIG. 3F , there is shown an embodiment of prosthetic “ribbon structure” valve  10   b  that is shown in  FIG. 3B , wherein the prosthetic “ribbon structure” valve, now denoted  10   e , includes multiple supplemental support structures (denoted “92”) that are disposed proximate the mid-region of prosthetic “ribbon structure” valve  10   e  to enhance the structural integrity of the prosthetic valve  10   e.    
     According to the invention, the supplemental support structures  92  can be disposed at any point on a prosthetic valve of the invention. 
     Referring now to  FIG. 3G , there is shown another embodiment of prosthetic “ribbon structure” valve  10   a  that is shown in  FIG. 3B , wherein the prosthetic valve, now denoted  10   f , is formed from and, hence, comprises two (2) seamless pre-formed sheet structures or members,  80   c ′,  80   c ″ i.e., a multi-sheet base “ribbon structure” valve member. 
     According to the invention, in some embodiments of the invention, the inner and outer sheet members  80   c ′,  80   c ″ can comprise sheet member  80   a  shown in  FIG. 2A , wherein prosthetic “ribbon structure” valve  10   f  is formed by positioning the adaptive support member  200  between the inner  80   c ′ and outer  80   c ″ sheet members. 
     In some embodiments of the invention, the inner sheet member  80   c ′ comprises sheet member  80   a  shown in  FIG. 2A  and the outer sheet member  80   c ″ comprises sheet member  80   b  shown in  FIG. 3A , such as illustrated in  FIG. 3G , wherein, when sheet members  80   c ′,  80   c ″ are folded inwardly and form prosthetic “ribbon structure” valve  10   f , support member  200  is similarly positioned between the inner  80   c ′ and outer  80   c ″ sheet members. 
     According to the invention, the support structure  200  can also be disposed proximate the inner surface of the inner sheet member  80   c′.    
     Referring now to  FIG. 3H , there is shown another embodiment of prosthetic “ribbon structure” valve  10   f  that is shown in  FIG. 3G , wherein the prosthetic valve, now denoted  10   g , comprises support structure  250 , and the annular ring  225  of the support structure  250  is disposed on the annular engagement end  65  of the prosthetic valve  10   g.    
     As illustrated in  FIG. 3H , in a preferred embodiment, the support structure  250  and, hence, annular ring  225  is similarly disposed between inner and outer sheet structures or members  80   c ′ and  80   c ″ of prosthetic “ribbon structure” valve  10   g.    
     However, as indicated above, according to the invention, the support structure  250  can similarly be disposed proximate the inner surface of the inner sheet structure  80   c ′ of prosthetic “ribbon structure” valve  10   g.    
     According to the invention, the prosthetic “ribbon structure” valve  10   b  (and, hence, prosthetic valves  10   c ,  10   d ,  10   e ,  10   f ,  10   g ,  10   h ) can further comprise a stent structure, such as described in Applicant&#39;s U.S. Pat. No. 10,188,513, which is incorporated by reference herein in its entirety. 
     Referring now to  FIGS. 4A and 4B , a further embodiment of a prosthetic “ribbon structure” valve of the invention having a multi-sheet base valve member will be described in detail. 
     As illustrated in  FIG. 4B , the prosthetic “ribbon structure” valve, denoted  10   h , comprises a first base valve member, denoted  10   a ′, and second base valve member, denoted  10   a ″, which, according to the invention, are similar to (and, hence, function similarly to) sheet member  10   a  shown in  FIG. 2A . However, in the illustrated embodiment, the first or outer base valve member  10   a ′ is formed from sheet member  80   b  shown in  FIG. 3A  (or a similar sheet member) and the second or inner base valve member  10   a ″ is formed from sheet member  80   b ′ shown in  FIG. 4A . 
     As illustrated in  FIG. 4A , the ribbon members  90  of the second or inner base valve member  10   a ″ are preferably shorter in length than the ribbon members  60  of the first or outer base valve member  10   a′.    
     As further illustrated in  FIG. 4A , except for the length, sheet member  80   b ′ is similar to sheet member  80   b , having adaptive support structure  200  positioned thereon. 
     According to the invention, the ribbon members  60  and  90  can similarly comprise various widths proximate the proximal ends  64  and  94  of ribbon members  60  and  90 . 
     Referring now to  FIGS. 5A and 5B , there is shown another embodiment of an adaptive support structure of the invention, denoted  300 . As illustrated in  FIGS. 5A and 5B , in a preferred embodiment, the adaptive support structure  300  comprises a base structure  310  and a plurality of elongated support members  302  having proximal and distal ends  306   a ,  306   b.    
     According to the invention, the support structure  300  can similarly comprise any of the aforementioned biocompatible metals, mammalian-based tissues and compositions formed therewith, and polymeric compositions. 
     In some embodiments of the invention, the adaptive support structure  300  is similarly configured to transition from a pre-deployment configuration, wherein a prosthetic “ribbon structure” valve associated therewith can be positioned proximate a valve annulus, to an expanded post-deployment configuration. 
     In such embodiments, when the adaptive support structure  300  transitions to the expanded post-deployment configuration, the adaptive support structure  300  will similarly conform to the annular engagement end of the prosthetic “ribbon structure” valves associated therewith, and, in some embodiments, a valve annulus when the annular engagement end of the prosthetic “ribbon structure” valves is in contact therewith. 
     According to the invention, transition of the adaptive support structure  300  from a pre-deployment configuration to a post-deployment configuration can similarly be achieved or induced by various conventional means. 
     Thus, in some embodiments of the invention, transition of the adaptive support structure  300  from a pre-deployment configuration to a post-deployment configuration is similarly achieved by applying a radial force to the adaptive support structure  300  and/or an interior region of the prosthetic “ribbon structure” valve associated therewith, such as by a conventional balloon catheter device. 
     In some embodiments of the invention, transition of the adaptive support structure  300  from a pre-deployment configuration to a post-deployment configuration is similarly achieved or induced by virtue of the adaptive support structure  300  composition, i.e., the adaptive support structure  200  comprises a shape-memory alloy, such as Nitinol®. 
     In a preferred embodiment, the adaptive support structure  300  is similarly designed, configured and adapted to exert at least one, more preferably, a plurality of retaining forces on the annular engagement ends of the prosthetic “ribbon structure” valves of the invention, whereby the adaptive support structure  300  similarly (i) conforms to the annular engagement ends of the prosthetic “ribbon structure” valves, (ii) securely positions the annular engagement ends of the prosthetic “ribbon structure” valves adjacent to and, thereby, in contact with a target valve annulus valve, whereby the annular engagement ends of the prosthetic “ribbon structure” valves conform to the shape of the valve annulus, and (iii) the annular engagement ends of the prosthetic “ribbon structure” valves and, thereby, the prosthetic “ribbon structure” valves adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus, whereby the annular engagement ends of the prosthetic “ribbon structure” valves maintain contact therewith. 
     In some embodiments of the invention, when the adaptive support structure  300  exerts the retaining force on the annular engagement ends of the prosthetic “ribbon structure” valves, the adaptive support structure  300  is further adapted to maintain contact of the annular engagement ends of the prosthetic “ribbon structure” valves to the valve annulus for a predetermined period of time. 
     According to the invention, the elongated support members  302  of the adaptive support structure  300  can similarly comprise any length and shape. In some embodiments, the elongated support members  302  comprise a length in the range of 20-200 mm, more preferably, a length in the range of 35-45 mm. 
     In some embodiments, the elongated support members  302  comprise alternating lengths in the range of 20-200 mm, more preferably, a length in the range of 35-45 mm. By way of example, an adaptive support structure comprising six (6) elongated support members can comprise three (3) elongated support members with a length of 38 mm and three (3) elongated support members with a length of 40 mm, where the elongated support members are arranged according to alternating length. 
     In a preferred embodiment, elongated support members  302  are also flexible. 
     In some embodiments, the elongated support members  302  are deformable. 
     As illustrated in  FIGS. 5A and 5C , in a preferred embodiment, the proximal ends  306   a  of the elongated support members  302  comprise looped structures  308  comprising anchored tips  310  and circumferential regions  312 . 
     As illustrated in  FIGS. 5A and 5B , the circumferential regions  312  of the elongated support members  302  can be configured to receive annular ring  225  (and, hence, annular ring  400 , discussed below), which is shown in phantom, and secure the annular ring  225  to the adaptive support structure  300 . 
     Referring now to  FIG. 5D , there is shown another embodiment of distal ends  306   a  of elongated support members  302 . As illustrated in  FIG. 5D , the distal ends  306   a  comprise an anchored distal end  313  having a deployable anchoring member  315 . 
     In some embodiments, the anchored end  313  is configured to transition from a recessed pre-deployment position to an extended post-deployment configuration, wherein the anchoring member  315  is deployed in an extended position. 
     According to the invention, the deployable anchoring member  315  can comprise any suitable anchoring mechanism that is configured to deploy an anchoring member that is adapted to engage tissue of a cardiovascular structure; particularly, a valve annulus, position a support structure and, hence, prosthetic valve of the invention associated therewith, proximate the cardiovascular structure, and maintain contact of the prosthetic valve to the cardiovascular structure. 
     According to the invention, the adaptive support structure  300  can comprise various configurations. Referring now to  FIGS. 6A-6E , there are shown five (5) alternative shapes and configurations and, hence, additional embodiments of the adaptive support structure  300  shown in  FIG. 5A . 
     Referring now to  FIG. 7A , there is shown another embodiment of an adaptive support structure  500  of the invention. 
     As illustrated in  FIG. 7A , adaptive support structure  500  comprises a multi-link support structure that comprises discontinuous, cross-linked circumferential proximal end regions  508 , a cylindrical distal end region  510 , and a plurality of elongated support members  502  that are positioned and configured to connect the cross-linked circumferential proximal end regions  508  to the cylindrical distal end region  510 . 
     Ina preferred embodiment, the elongated support members  502  comprise flexible members. In some embodiments, the elongated support members  502  are deformable. 
     According to the invention, the adaptive support structure  500  can similarly comprise any of the aforementioned biocompatible metals, mammalian-based tissues (and compositions comprising same, e.g., an ECM composition), and polymeric compositions. 
     In some embodiments, the adaptive support structure  500  similarly comprises a nickel-titanium alloy, such as Nitinol®. 
     In a preferred embodiment, the adaptive support structure  500  is similarly configured to transition from a pre-deployment configuration, wherein the ends  514  of the discontinuous, cross-linked circumferential proximal end regions  508  are in communication with each other and a prosthetic “ribbon structure” valve associated therewith can be disposed in a valve annulus, to a post-deployment configuration, such as shown in  FIG. 7B , wherein the prosthetic “ribbon structure” valve associated therewith can be positioned proximate a valve annulus, to an expanded post-deployment configuration. 
     In some embodiments, the cross-linked circumferential proximal end regions  508  of the adaptive support structure  500  comprise magnetized ends  514  that are configured to self-align and maintain communication with each other when the adaptive support structure  500  (and, hence, prosthetic “ribbon structure” valve associated therewith) is in a pre-deployment configuration. 
     According to the invention, transition of the adaptive support structure  500  from a pre-deployment configuration to a post-deployment configuration can similarly be achieved or induced by various conventional means. 
     Thus, in some embodiments of the invention, transition of the adaptive support structure  500  from a pre-deployment configuration to a post-deployment configuration is similarly achieved by applying a radial force to the adaptive support structure  500  and/or an interior region of the prosthetic “ribbon structure” valve associated therewith, such as by a conventional balloon catheter device. 
     In some embodiments of the invention, transition of the adaptive support structure  500  from a pre-deployment configuration to a post-deployment configuration is similarly achieved or induced by virtue of the adaptive support structure  500  composition, i.e., the adaptive support structure  500  comprises a shape-memory alloy, such as Nitinol®. 
     Ina preferred embodiment, the adaptive support structure  500  is similarly designed, configured and adapted to exert at least one, more preferably, a plurality of retaining forces on the annular engagement ends of the prosthetic “ribbon structure” valves of the invention, whereby the support structure  500  similarly (i) conforms to the annular engagement end of prosthetic “ribbon structure” valves, (ii) securely positions the annular engagement ends of the prosthetic “ribbon structure” valves adjacent to and, thereby, in contact with a target valve annulus valve, whereby the annular engagement ends of the prosthetic “ribbon structure” valves conform to the shape of the valve annulus, and (iii) the annular engagement ends of the prosthetic “ribbon structure” valves and, thereby, the prosthetic “ribbon structure” valves adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus, whereby the annular engagement ends of the prosthetic “ribbon structure” valves maintain contact therewith. 
     In some embodiments of the invention, when the adaptive support structure  500  exerts retaining force(s) on the annular engagement ends of the prosthetic “ribbon structure” valves, the adaptive support structure  500  is further adapted to maintain contact of the annular engagement ends of the prosthetic “ribbon structure” valves to the valve annulus for a predetermined period of time. 
     Referring now to  FIG. 7B , there is shown one embodiment of prosthetic “ribbon structure” valve, denoted  10   i , wherein the prosthetic “ribbon structure” valve  10   i  comprises base valve member  10   a  and the adaptive support structure  500  shown in  FIG. 7A . 
     Referring now to  FIGS. 8A and 8B , there is shown a further embodiment of a support structure of the invention, denoted  600 . 
     As illustrated in  FIGS. 8A and 8B , the support structure  600  comprises an expandable annular ring member  602 . 
     According to the invention, the expandable annular ring member  602  can be employed in or with adaptive support structures  200  and  250 , i.e., a component thereof, or as a separate support structure. 
     As illustrated in  FIGS. 8A and 8B , in one embodiment, the annular ring member  602  preferably comprises at least one helically arranged fiber or cord element  601 . In a preferred embodiment, the annular ring member  602  comprises a plurality of helically arranged fiber or cord elements  601 , which form an expandable tubular ring configuration having a plurality of uniformly shaped closed, interconnecting cells  604 . 
     According to the invention, the fiber elements  601 , and, hence, annular ring member  602  formed therefrom, can comprise any of the aforementioned biocompatible metals, mammalian-based tissues (and compositions comprising same), and polymeric compositions. 
     In some embodiments, the fiber elements  601  comprise a nickel-titanium alloy, such as Nitinol®. 
     In some embodiments of the invention, the fiber elements  601  comprise Dyneema®, a high molecular weight polyethylene (HMPE). 
     As further illustrated in  FIGS. 8A and 8B , in a preferred embodiment, the annular ring member  602  and, hence, expandable annular ring  600  is configured and adapted to transition from a pre-deployment configuration, wherein, as illustrated in  FIG. 8A , the annular ring comprises a width w 1  and a diameter d 1 , to a post-deployment configuration, wherein, as illustrated in  FIG. 8B , the annular ring comprises a greater width w 2  and a greater diameter d 2 , whereby, when the expandable annular ring  600  is disposed proximate an annular engagement end of a prosthetic “ribbon structure” valve of the invention, such as prosthetic “ribbon structure” valve  10   a , the expandable annular ring  600  conforms to the annular engagement end of the prosthetic “ribbon structure” valve. 
     In a preferred embodiment, the expandable annular ring  600 , when in the post-deployment configuration, is further similarly adapted to exert a retaining force on the annular engagement ends of the prosthetic “ribbon structure” valves of the invention, whereby the expandable annular ring  600  similarly (i) positions the annular engagement ends of the prosthetic “ribbon structure” valves adjacent to and, thereby, in contact with a target valve annulus, (ii) the annular engagements ends of the prosthetic “ribbon structure” valves conform to the shape of the valve annulus, and (iii) the annular engagement ends of the prosthetic “ribbon structure” valves and, thereby, the prosthetic “ribbon structure” valves adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus, whereby the annular engagement ends of the prosthetic “ribbon structure” valves maintain contact therewith. 
     In some embodiments of the invention, when the expandable annular ring  600  exerts retaining force(s) on the annular engagement ends of the prosthetic “ribbon structure” valves, the expandable annular ring  600  is further adapted to maintain contact of the annular engagement ends of the prosthetic “ribbon structure” valves to the valve annulus for a predetermined period of time. 
     According to the invention, transition of the expandable annular ring  600  from a pre-deployment configuration to a post-deployment configuration can be achieved by various means. 
     In some embodiments of the invention, transition of the expandable annular ring  600  from a pre-deployment configuration to a post-deployment configuration is achieved by applying a radial force to the interior portion  606  of an expandable annular ring  602 , such as by a conventional balloon catheter device. 
     In some embodiments of the invention, transition of the expandable annular ring  600  from a pre-deployment configuration to a post-deployment configuration is achieved or induced by virtue of the expandable annular ring  602  composition, i.e., the expandable annular ring  602  comprising a shape-memory alloy, such as Nitinol®. 
     In some embodiments of the invention, transition of the expandable annular ring  600  from a pre-deployment configuration to a post-deployment configuration is achieved or induced by a radial force provided and exerted to the interior portion  606  of the expandable annular ring  600  by the elongated support members of the adaptive support structures of the invention. 
     In some embodiments of the invention, the transition of the expandable annular ring  600  and, thereby, adaptive support structure  250 , from a pre-deployment configuration to an expanded post-deployment configuration is achieved or induced by virtue of the configuration of the annular ring  225 , e.g., an overlapping expandable band configuration. 
     Referring now to  FIG. 9A , there is shown prosthetic “ribbon structure” valve  10   d  disposed in an abnormally expanded mitral valve annulus region  102   a  of a subject. 
     As illustrated in  FIG. 9A  and discussed in detail above, the support structure  250  and, hence, annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  is configured to (i) conform to the configuration and dimension of the abnormally expanded mitral valve annulus region  102   a  and (ii) adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus  102   a , whereby the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  maintains contact with (and maintains an effective seal with) the valve annulus  102   a.    
     As illustrated in  FIG. 9B , the support structure  250  and, hence, annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  is further adapted to (i) allow the expanded mitral valve annulus region  102   a  to return to a physiologically healthy valve annulus region state and, hence, size (denoted  102   b ), and (ii) maintain contact of the annular engagement end  65  of prosthetic “ribbon structure” valve  10   d  to the annulus region  102   b.    
     According to the invention, the prosthetic “ribbon structure” valves and associated adaptive support structures of the invention can be delivered to or implanted in a subject using any conventional procedure. 
     In a preferred embodiment of the invention, the prosthetic “ribbon structure” valves and associated adaptive support structures of the invention are delivered to or implanted in a subject using a percutaneous implantation procedure. 
     In some embodiments, the prosthetic “ribbon structure” valves and associated adaptive support structures of the invention are delivered to or implanted in a subject using at least one system or method of implantation disclosed in Applicant&#39;s U.S. application Ser. No. 16/553,570, which is incorporated by reference herein in its entirety. 
     According to the invention, the prosthetic “ribbon structure” valves and associated adaptive support structures of the invention can be configured to have any suitable pre-deployment size and configuration. In some embodiments, the prosthetic “ribbon structure” valves and associated adaptive support structures of the invention are configured to compress down to a pre-deployment size of at least 6 French (a circumference of at least 6.28 mm). 
     As will readily be appreciated by one having ordinary skill in the art, the present invention provides numerous advantages compared to prior art prosthetic valves. Among the advantages are the following:
         The provision of prosthetic valves having an adaptable or dynamic annular engagement end or region adapted to engage a valve annulus, which will accommodate a broad range of valve annulus configurations and dimensions, and adapt to at least one fluctuation in the configuration and/or dimension of the valve annulus in vivo, whereby, the annular engagement end or region of the valves maintains sealed engagement to the valve annulus;   The provision of prosthetic valves having means for secure, reliable, and consistent highly effective attachment to cardiovascular structures and/or tissue;   The provision of prosthetic valves that significantly decrease or effectively eliminate the incidence of perivalvular leaks after implant in a subject;   The provision of improved methods for attaching prosthetic valves to cardiovascular structures and/or tissue that significantly decrease or effectively eliminate the incidence of perivalvular leaks;   The provision of improved prosthetic valves and methods for attaching same to cardiovascular structures and/or tissue that maintain or enhance the structural integrity of the valve when subjected to cardiac cycle induced forces;   The provision of improved prosthetic valves and methods for attaching same to cardiovascular structures and/or tissue that preserve the structural integrity of the cardiovascular structure(s) when attached thereto;   The provision of prosthetic valves that induce modulated healing, including host tissue proliferation, bioremodeling and regeneration of new tissue and tissue structures with site-specific structural and functional properties;   The provision of prosthetic valves that induce adaptive regeneration in vivo;   The provision of prosthetic valves that are capable of administering a pharmacological agent to host tissue and, thereby produce a desired biological and/or therapeutic effect;   The provision prosthetic valves that can be implanted without removal of the native AV valve;   The provision prosthetic valves that can be implanted without a cardiopulmonary bypass apparatus;   The provision prosthetic valves that can be positioned proximate a valve annulus, transvascularly; and   The provision prosthetic valves that can be positioned proximate a valve annulus, transapically.       

     Without departing from the spirit and scope of this invention, one of ordinary skill can make various changes and modifications to the invention to adapt it to various usages and conditions. As such, these changes and modifications are properly, equitably, and intended to be, within the full range of equivalence of the following claims.