(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2013/0310929 A1
`Dove et al.
`(43) Pub. Date: NOV. 21, 2013
`
`
`US 20130310929A1
`
`(54) METHODS OF CONDITIONING SHEET
`BIOPROSTHETIC TISSUE
`
`(71) Applicant: Edwards Lifesciences Corporation,
`Irvine, CA (US)
`
`(72)
`
`Inventors: Jeffrey S. Dove, Santa Ana, CA (US);
`Bin Tian, Irvine, CA (US); Ralph
`Schneider, Trabuco Canyon, CA (US);
`Jeffrey S. Cohen, Irvine, CA (US); Ivan
`Jankovic, Costa Mesa, CA (US); John
`F. Migliazza, Belmont Shore, CA (US);
`Gregory A. Wright, Orange, CA (US);
`James Young, Ladera Ranch, CA (US);
`Louis A. Campbell, Santa Ana, CA (US)
`
`(73) Assignee: EDWARDS LIFESCIENCES
`CORPORATION, Irvine, CA (US)
`
`(21) Appl.No.: 13/950,154
`
`(22)
`
`Filed:
`
`Jul. 24, 2013
`
`Related US. Application Data
`
`(63) Continuation of application No. 13/069,827, filed on
`Mar. 23, 2011.
`
`(60) Provisional application No. 61/316,801, filed on Mar.
`23, 2010, provisional application No. 61/381,858,
`filed on Sep. 10, 2010.
`Publication Classification
`
`(51)
`
`Int. Cl.
`A61F2/24
`(52) U.S.Cl.
`CPC .................................... A61F2/2415(2013.01)
`USPC ........................... 623/2.13; 264/299; 264/138
`
`(2006.01)
`
`ABSTRACT
`(57)
`Methods for the conditioning of bioprosthetic material
`employ bovine pericardial membrane. A laser directed at the
`fibrous surface of the membrane and moved relative thereto
`
`reduces the thickness of the membrane to a specific uniform
`thickness and smoothes the surface. The wavelength, power
`and pulse rate of the laser are selected which will smooth the
`fibrous surface as well as ablate the surface to the appropriate
`thickness. Alternatively, a dermatome is used to remove a
`layer of material from the fibrous surface of the membrane.
`Thinning may also employ compression. Stepwise compres-
`sion with cross-linking to stabilize the membrane is used to
`avoid damaging the membrane through inelastic compres-
`sion. Rather, the membrane is bound in the elastic com-
`pressed state through addition cross-linking. The foregoing
`several thinning techniques may be employed together to
`achieve strong thin membranes.
`
`
`
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`
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`
`
`
`Edwards Lifesciences v. Boston Scientific
`
`IPR2017-00444 EX. 2035 Page 1 of 16
`
`US. Patent No. 6,915,560
`
`Page 1 of 16
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`

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`Patent Application Publication
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`Nov. 21, 2013 Sheet 1 0f 5
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`US 2013/0310929 A1
`
`Fig.1(PriorArt)
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`Patent Application Publication
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`NOV. 21, 2013 Sheet 2 0f 5
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`US 2013/0310929 A1
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`Patent Application Publication
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`Nov. 21, 2013 Sheet 3 0f 5
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`US 2013/0310929 A1
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`Patent Application Publication
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`Nov. 21, 2013 Sheet 4 0f 5
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`US 2013/0310929 A1
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`Patent Application Publication
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`Nov. 21, 2013 Sheet 5 of 5
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`US 2013/0310929 A1
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`

`US 2013/0310929 A1
`
`Nov. 21,2013
`
`METHODS OF CONDITIONING SHEET
`BIOPROSTHETIC TISSUE
`
`RELATED APPLICATIONS
`
`[0001] The present application is a continuation of US.
`patent application Ser. No. 13/069,827, filed Mar. 23, 2011,
`which claims priority under 35 U.S.C. §119(e) to US. Pro-
`visional Application Ser. No. 61/316,801 filed on Mar. 23,
`2010, and to US. Provisional Application Ser. No. 61/381,
`858 filed on Sep. 10, 2010.
`
`FIELD OF THE INVENTION
`
`[0002] The field ofthe present invention is the conditioning
`ofbioprosthetic tissues for use in implants and, more particu-
`larly, for methods for smoothing and thinning sheet biopros-
`thetic tissue for use in prosthetic heart valves.
`
`BACKGROUND OF THE INVENTION
`
`technology has long been capable of
`[0003] Medical
`replacing damaged or diseased heart valves through open
`heart surgery. Such valves have included mechanical devices
`as well as those using biological material from humans (ho-
`mograft tissue) and animals (xenograft tissue). The two pri-
`mary types of prosthetic heart valves known in the art are
`mechanical valves and bioprosthetic valves. Bioprosthetic
`valves may be formed from an intact, multi-leaflet porcine
`(pig) heart valve, or by shaping a plurality of individual
`flexible leaflets out ofbovine pericardial tissue or other mate-
`rials, and combining the leaflets to form the valve. One advan-
`tage of bioprosthetic valves, unlike mechanical valves, is that
`the patient receiving the valve typically does not require long
`term treatment with anticoagulants.
`[0004] The pericardium is a sac around the heart of verte-
`brate animals which contains lubricating fluid, and bovine
`(cow) pericardium is commonly used to make individual
`leaflets for prosthetic heart valves. The bovine pericardium is
`first harvested from the animal and then chemically fixed to
`crosslink collagen and elastin molecules in the tissue and
`increase the tissue durability, before being cut into leaflets.
`[0005] A good discussion ofthe various physical properties
`of fixed bovine pericardium is given in Simionescu, et al,
`Mapping of Glutaraldehyde-Treated Bovine Pericardium and
`Tissue Selection For Bio-prosthetic Heart Valves, Journal of
`Bio-Medical Materials Research, Vol. 27, 697-704, John
`Wiley & Sons, Inc., 1993. Simionescu, et al., recognized the
`sometimes striking variations in physical properties of the
`pericardial tissue, even in the same pericardial sac.
`[0006] The pericardial sac consists oftwo distinct elements
`of tissue. The visceral or serous layer is of very thin translu-
`cent tissue most adjacent the heart which is not used to con-
`struct artificial heart valve leaflets. This inner layer of the
`pericardium is conical and surrounds the heart and the roots of
`the great blood vessels. The parietal pericardial membrane is
`a thicker membrane of multi-layered connective tissue cov-
`ered with adipose tissue. The outside fat/adipose tissue is
`removed (e.g., peeled off) when harvested. The remaining
`multi-layered fibrous tissue primarily contains collagen
`fibers with a generally fibrous outer surface and a smooth
`inner surface. This remaining membrane is used for making
`the leaflets for artificial heart valves.
`
`[0007] A number of steps in a typical commercial process
`for preparing pericardial tissue for heart valve leaflets are
`illustrated in FIG. 1. First, a fresh pericardial sac 20 is
`
`obtained from a regulation slaughterhouse. The sac 20 is then
`cut open along predetermined anatomical landmarks, as indi-
`cated at 22. The sac is then flattened at 24 and typically
`cleaned of excess fat and other impurities. After trimming
`obviously unusable areas, a window 26 of tissue is fixed,
`typically by immersing in an aldehyde to cross-link the tissue,
`and then quarantined for a period of about two weeks. Nor-
`mally, two windows of 4 to 6 inches on a side can be obtained
`from one bovine pericardial sac. Rough edges of the tissue
`window 26 are removed and the tissue bio-sorted to result in
`
`a tissue section 28. The process of bio-sorting involves visu-
`ally inspecting the window 26 for unusable areas, and trim-
`ming the section 28 therefrom. Subsequently, the section 28 is
`further cleaned as indicated at 30.
`
`[0008] The section 28 is then placed flat on a platform 32
`for thickness measurement using a contact indicator 34. The
`thickness is measured by moving the section 28 randomly
`around the platform 32 while a spindle 36 of the indicator 34
`moves up-and-down at various points. The thickness at each
`point is displayed at 38 and recorded by the operator. After
`sorting the measured sections 28 by thickness, as indicated at
`40, leaflets 42 are die cut from the sections, with thinner
`leaflets 42 generally being used for smaller valves, and
`thicker leaflets being used for larger valves. Of course, this
`process is relatively time-consuming and the quality of the
`final leaflets is dependent at several steps on the skill of the
`technician. Moreover, the number of leaflets obtained from
`each sac is inconsistent, and subject to some inefficiency from
`the manual selection process. One solution to this time-con-
`suming manual process is provided inU.S. Pat. No. 6,378,221
`to Ekholm, et al., in which a three-axis programmable con-
`troller manipulates a pericardial sheet with respect to a thick-
`ness measurement head to topographically map the sheet into
`similar thickness zones for later use. However, even with
`advanced methods the variability of the bovine pericardium
`results in an extremely low yield of sheet usable for heart
`valve leaflets; averaging less than 2 sheets per sac.
`tissue
`[0009] Typically, harvested bovine pericardial
`ranges in thickness from 250 microns up to 700 microns,
`though most of the material is between 300-700 microns
`thick.
`
`[0010] Valves using flexible leaflets, such as those made of
`bovine pericardial tissue, have acquired increased signifi-
`cance of late because these valves may be implanted by other
`than open heart surgery. The valves are constructed using
`radially expandable stents with flexible (e.g., pericardial)
`leaflets attached. Implant methods include compressing the
`valve radially by a significant amount to reduce its diameter
`or delivery profile, inserting the valve into a delivery tool,
`such as a catheter or cannula, and advancing the delivery tool
`to the correct anatomical position in the heart. Once properly
`positioned, the valve is deployed by radial expansion within
`the native valve annulus, either through self-expanding stent
`structure or with an expansion balloon. The collapsed valve in
`the catheter may be introduced through the vasculature, such
`as through the femoral artery, or more directly through an
`intercostal incision in the chest. The procedure can be accom-
`plished without open heart surgery and possibly without stop-
`ping the heart during the procedure.
`[0011] One example ofpercutaneous heart valve delivery is
`US. Pat. No. 6,908,481 to Cribier and Edwards Lifesciences
`of Irvine, Calif., which shows a valve prosthesis with an
`expandable frame on which a collapsible valvular structure is
`mounted. Another compressible/expandable heart valve is
`
`Page 7 of 16
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`

`

`US 2013/0310929 A1
`
`Nov. 21,2013
`
`shown in U.S. Patent Publication No. 2010/0036484, also
`from Edwards Lifesciences. Further examples of such meth-
`ods and devices are disclosed in U.S. Pat. No. 7,621,948 and
`US Patent Publication No. 2006/0259136, and the number of
`other configurations of such valves is exploding as the prom-
`ise of the technology grows. The disclosures of each of these
`references are incorporated herein by reference.
`[0012] These new devices require thinner components that
`enable crimping of the valve down to a size that can pass
`through the delivery tool. One limiting component is the
`thickness of the bioprosthetic tissue. As mentioned, pericar-
`dial layers range from 250-700 microns, but only a small
`percentage of the harvested pericardium falls close to the low
`end, which is the most useful for compressible/expandable
`valves.
`
`[0013] U.S. Pat. No. 7,141,064 proposes compressing
`bovine pericardium to reduce its thickness by about 50 per-
`cent for use in heart valve leaflets. The compression may also
`smooth out the tissue surface to reduce thickness non-unifor-
`mity.
`[0014] Despite much research into various bioprosthetic
`tissue, in particular for heart valve leaflets, there remains a
`need for thinner and more consistent thickness tissues for use
`
`in fabricating smaller delivery profile bioprostheses.
`
`SUMMARY OF THE INVENTION
`
`[0015] The present invention is directed to the preparation
`of bioprosthetic material for cardio implantation. Bovine
`pericardial membrane having a fibrous surface and a smooth
`surface are selected. This preparation can increase the yield of
`cardio valve leaflets from pericardial membrane and can
`eliminate thrombogenic agents such as dangling fibers.
`[0016]
`In accordance with one aspect, a method for prepar-
`ing bioprosthetic tissue membrane material includes first
`selecting a tissue membrane (e.g., bovine pericardial mem-
`brane) having a fibrous side and a smooth side. Material is
`then removed from the fibrous side ofthe selected membrane
`to reduce the thickness of the membrane and smooth the
`
`fibrous side. The material may be removed by shearing with a
`mechanical device, such as a dermatome or vibratome. Alter-
`natively, the material may be removed by ablation with a
`laser.
`
`In the just-described method, the selected mem-
`[0017]
`brane may be conditioned by compressing the selected tissue
`membrane and cross-linking the material of the membrane
`while under compression. Furthermore,
`the method may
`involve treating the membrane reduced in thickness by cap-
`ping of calcification nucleation sites and/or by borohydride
`reduction. In accordance with one aspect, the method further
`comprises at least partially fixing the selected membrane
`prior to the removing step.
`[0018]
`In accordance with another method disclosed
`herein, biopro sthetic tissue membrane material is prepared by
`first selecting a tissue membrane having a fibrous side and a
`smooth side, conditioning the selected tissue membrane by
`compression and cross-linking the membrane while under
`compression, and then removing conditioned material from
`the fibrous side ofthe selected tissue membrane to reduce the
`thickness of the membrane and smooth the fibrous side. The
`
`tissue membrane maybe pericardial membrane, such as
`bovine or equine. The method may involve treating the mem-
`brane reduced in thickness by capping and/or by borohydride
`reduction. In accordance with one aspect, the step of remov-
`ing is accomplished by shearing with a mechanical device,
`
`such as a dermatome or vibratome. Or, the step ofremoving is
`accomplished by ablating the conditioned material with a
`laser.
`
`In accordance with a still further aspect, a method
`[0019]
`for preparing bioprosthetic tissue membrane material com-
`prises first selecting a tissue membrane having a fibrous side
`and a smooth side. The material of the membrane is the least
`
`partially cross-linked, and then infused with a second cross-
`linking material of a chain length to allow spending of large
`inter-fibril domains. Subsequently, the tissue membrane is the
`least partially compressed. The tissue membrane may be
`bovine pericardial membrane. The method may also involve
`lightly compressing the selected membrane prior to at least
`partially cross-linking the membrane. The method may
`include treating the membrane reduced in thickness by cap-
`ping and/or by borohydride reduction. In accordance with one
`aspect, material is removed from the fibrous side ofthe lightly
`compressed tissue membrane.
`[0020] Another aspect of the present application is a heart
`valve comprising a plurality of leaflets each made of sheet
`tissue having a first region with a uniform first thickness and
`a second region with a uniform second thickness greater than
`the first thickness. The leaflets preferably each have a cusp
`edge opposite a free edge, and the second region extends in a
`generally uniform width strip along the cusp edge. The sec-
`ond region also may extend in a generally uniform width strip
`along the free edge of each leaflet. Furthermore, the second
`region may extend in generally uniform width strips radially
`from the center of the free edge to the cusp edge. Desirably,
`transitions between the thicknesses of the first and second
`
`the heart valve
`regions is gradual. In one embodiment,
`includes a support frame to which peripheral edges of the
`leaflets attach with sutures, and the second region extends
`along the leaflet edges through which sutures are passed.
`[0021]
`In a first separate aspect of the invention, a der-
`matome is employed with the fibrous surface of the mem-
`brane and moved relative thereto to smooth the surface and/or
`
`reduce the thickness of the membrane to a specific uniform
`thickness, for instance no more than 250 microns. The der-
`matome is constrained by spacers to control the thickness of
`the membrane remaining with the shaved material removed.
`[0022]
`In a second separate aspect of the invention, the
`fibrous surface of the membrane is removed to smooth the
`surface and/or reduce the thickness of the membrane to a
`
`specific uniform thickness. The membrane is first subjected to
`light compression and cross-linking to smooth the fibrous
`surface and improve the material for ablation.
`[0023]
`In a third separate aspect of the invention, a laser is
`directed at the fibrous surface of the membrane and moved
`relative thereto to ablate the surface to smooth the surface
`
`and/or reduce the thickness of the membrane to a specific
`uniform thickness. The wavelength, power and pulse rate of
`the laser are selected which will smooth the fibrous surface as
`
`well as ablate the surface to the appropriate thickness. The
`membrane may first be subjected to light compression and
`cross-linking to smooth the fibrous surface and improve the
`material for ablation.
`
`In a fourth separate aspect of the present invention,
`[0024]
`the selected bovine pericardial membrane is first at least
`partially cross-linked, then infused with a second cross-link-
`ing material of a chain length to allow spanning of large
`inter-fibril domains. The membrane is then compressed, and
`may then be treated by capping and borohydride reduction.
`
`Page 8 of 16
`
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`

`

`US 2013/0310929 A1
`
`Nov. 21,2013
`
`In a fifth separate aspect of the present invention,
`[0025]
`any ofthe foregoing processes may be used in combination to
`greater advantage.
`[0026] A further understanding of the nature and advan-
`tages of the present invention are set forth in the following
`description and claims, particularly when considered in con-
`junction with the accompanying drawings in which like parts
`bear like reference numerals.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0027] The invention will now be explained and other
`advantages and features will appear with reference to the
`accompanying schematic drawings wherein:
`[0028]
`FIG. 1 illustrates a sequence of prior art steps for
`preparing and measuring the thickness of bovine pericardial
`tissue prior to forming leaflets from the tissue;
`[0029]
`FIG. 2 is a perspective view of a representative
`embodiment ofa prosthetic heart valve that may be made with
`tissue conditioned in accordance with the present application;
`[0030]
`FIG. 3 is a perspective view of a support frame that
`can be used in the prosthetic valve of FIG. 2;
`[0031]
`FIG. 4 is a flattened view of a leaflet of the valve
`shown in FIG. 2;
`[0032]
`FIG. 5 is a bottom perspective view of a valve leaflet
`structure connected to a reinforcing skirt so as to form a leaflet
`assembly;
`[0033]
`FIG. 6A depicts a side view of an exemplary pros-
`thetic heart valve crimped on a balloon delivery catheter;
`[0034]
`FIG. 6B shows the prosthetic valve of FIG. 6A
`mounted on the balloon delivery catheter and in its expanded
`state;
`FIG. 7 is a schematic view of a sequence of tissue
`[0035]
`conditioning of pericardial membrane with laser ablation;
`[0036]
`FIG. 8 is a flattened plan view of a valve leaflet
`showing a reinforcing region formed by uniformly thick tis-
`sue adjacent the bottom edge of the leaflet;
`[0037]
`FIG. 9 is an edge view of a valve leaflet showing a
`reinforcing region;
`[0038]
`FIG. 10 is a plan view of a prosthetic heart valve
`leaflet having a thickened peripheral edge in areas where
`sutures penetrate for attachment to a structural stent;
`[0039]
`FIGS. 10A and 10B are sectional views through a
`radial midline of the leaflet of FIG. 10 showing two different
`thickness profiles;
`[0040]
`FIG. 11 is a plan view of a prosthetic heart valve
`leaflet having a thickened peripheral edge in areas where
`sutures penetrate for attachment to a structural stent as well as
`a thickened free edge to reduce the risk of elongation at that
`location;
`FIGS. 11A and 11B are sectional views through a
`[0041]
`radial midline of the leaflet of FIG. 11 showing two different
`thickness profiles;
`[0042]
`FIG. 12 is a plan view of a prosthetic heart valve
`leaflet having a thickened peripheral edge in areas where
`sutures penetrate for attachment to a structural stent as well as
`a thickened triple point area in the free edge simulating nod-
`ules of Arantius;
`[0043]
`FIGS. 12A and 12B are sectional views through a
`radial midline of the leaflet of FIG. 12 showing two different
`thickness profiles;
`[0044]
`FIG. 13 illustrates in plan view an alternative leaflet
`having a thickened peripheral edge region, a thickened strip
`along the free edge, and a plurality of thickened radial strips
`extending from the free edge to the cusp edge;
`
`FIGS. 14A and 14B are schematic views of exem-
`[0045]
`plary leaflet skiving processes utilizing contoured forming
`molds;
`FIG. 15A is a schematic view of a dermatome cut-
`[0046]
`ting tissue, while FIG. 15B illustrates the result on a generic
`section of pericardial tissue;
`[0047]
`FIG. 16 is a schematic side view of a press with the
`near spacer removed for clarity.
`
`DETAILED DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`
`In the primary embodiment, the preparation of leaf-
`[0048]
`lets for prosthetic heart valves, in particular expandable heart
`valves, is described. The leaflets are desirably incorporated in
`expandable prosthetic heart valves that are initially crimped
`(or even rolled) into a small delivery profile or diameter to be
`passed through a catheter or other delivery system and then
`expanded at the implantation site, typically a valve annulus.
`The heart valves comprise structural stent bodies with a plu-
`rality of flexible leaflets incorporated therein. Various mate-
`rials are suitable for the stent body, although certain nickel-
`titanium alloys (i.e., Nitinol) are preferred for their super-
`elasticity and biocompatibility. It should also be noted that
`specific stent body configurations are not to be considered
`limiting, and various construction details may be modified.
`[0049] Although forming prosthetic heart valve leaflets to
`be thinner helps reduce the delivery size of expandable
`valves, forming thinner leaflets as well as conditioning the
`leaflets as described herein is believed to be advantageous for
`conventional heart valves as well. For example, smoothing
`the rough surface of pericardial tissue is believed to improve
`durability of the leaflets by reducing loose fibers and atten-
`dant thrombogenicity.
`[0050] Heart valves with durability in excess of 10 years
`have had bovine pericardial leaflet thicknesses ranging from
`0014-0023 inches (~350-580 microns), with smaller valves
`utilizing thinner leaflets and larger valves having thicker leaf-
`lets. Current percutaneous valves may employ porcine peri-
`cardial tissue with thicknesses down to 0004-0005 inches
`
`(~100-130 microns). Although naturally-occurring porcine
`tissue is somewhat thinner than naturally occurring pericar-
`dial tissue, there are certain advantages to using pericardial
`leaflets.
`
`[0051] Various tissues may be used for the leaflets, though
`a preferred tissue for use in the primary application of heart
`valve leaflets is bovine parietal pericardial membrane.
`Though the thickness and strength of bovine pericardial tis-
`sue is considered desirable for longer lasting valves, other
`bioprosthetic tissue such as porcine, equine and other mam-
`malian pericardium, including human, may be used. Further-
`more, tissue from other anatomical sources may be used, such
`as dura mater, peritonium, diaphragm, or others. Any tissue
`membrane that has a suitable durability and elasticity as peri-
`cardium is a candidate, though those of skill in the art will
`appreciate that certain materials may be better suited for any
`one specific application. In general,
`tissues that contain
`fibrous collagen, in particular classed as Type I or Type III
`collagen, and elastic fibers or elastin may be suitable for use
`in fabricating heart valve leaflets. Other potential types of
`collagen that can be used are hybrid natural collagen solution
`or electrospun collagen elastin fabric. Also, certain so-called
`engineered tissue may be used, which are synthesized by
`growing collagenous tissue over a typically mesh frame or
`scaffold. These source are collectively referred to as “tissue
`
`Page 9 of 16
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`

`US 2013/0310929 A1
`
`Nov. 21,2013
`
`from the principles
`membranes,” and may all benefit
`described herein, though some like bovine pericardium is
`especially well-suited for conditioning heart valve leaflets in
`accordance with the present application.
`[0052] As mentioned above, the pericardial sac consists of
`two or more distinct layers, one side being relatively smooth
`while the opposite surface comprises connective tissue cov-
`ered with adipose tissue, some of which is peeled off when
`harvested, and is thus fibrous. The methods described herein
`are particularly useful for smoothing out the fibrous side to
`form a consistently thick and smooth membrane. In some
`cases, the thickness ofthe fibrous adipose tissue side may also
`be reduced to produce a uniformly thin membrane, preferably
`below 300 microns for use in collapsible/expandable valves.
`[0053] With reference to FIG. 2, an exemplary one-piece
`prosthetic heart valve 50 is shown that can utilize a bovine
`membrane of uniform thickness. The valve 50 will be
`described in some detail to illustrate some of the benefits of
`the leaflet fabrication methods described herein, but more
`specifics on the valve structure may be found in US. Patent
`Publication No. 2010/0036484, filed Jun. 8, 2009, entitled
`“LOW PROFILE TRANSCATHETER HEART VALVE,”
`and assigned to Edwards Lifesciences,
`the disclosure of
`which is incorporated herein by reference. Alternatively,
`another minimally-invasive valve that may utilize thin peri-
`cardial membrane is found in US. Pat. No. 6,733,525, issued
`May 1 1, 2004, entitled “ROLLED MINIMALLY INVASIVE
`HEART VALVES AND METHODS OF USE,” which disclo-
`sure is expressly incorporated herein by reference.
`[0054] Valve 50 in the illustrated embodiment generally
`comprises a structural frame, or stent 52, a flexible leaflet
`structure 54 supported by the frame, and a flexible skirt 56
`secured to the outer surface of the leaflet structure. The illus-
`
`trated valve 50 may be implanted in the annulus of the native
`aortic valve, but also can be adapted to be implanted in other
`native valves of the heart or in various other ducts or orifices
`
`of the body. Valve 50 has a “lower” or inflow end 60 and an
`“upper” or outflow end 62. Blood flows upward freely
`through the valve 50, but the flexible leaflet structure 54
`closes to prevent reverse downward flow. The flexible leaflet
`structure 54 thus provides flexible fluid occluding surfaces to
`enable one-way blood flow.
`[0055] Valve 50 and frame 52 are configured to be radially
`collapsible to a collapsed or crimped state for introduction
`into the body on a delivery catheter and radially expandable to
`an expanded state for implanting the valve at a desired loca-
`tion in the body (e.g., the native aortic valve). Frame 52 can be
`made ofa plastically-expandable material that permits crimp-
`ing ofthe valve to a smaller profile for delivery and expansion
`of the valve using an expansion device such as the balloon of
`a balloon catheter. Exemplary plastically-expandable mate-
`rials include, without limitation, stainless steel, a nickel based
`alloy (e. g., a nickel-cobalt-chromium alloy), polymers, or
`combinations thereof. Alternatively, valve 50 can be a so-
`called self-expanding valve wherein the frame is made of a
`self-expanding material such as Nitinol. A self-expanding
`valve can be crimped and held in the collapsed state with a
`restraining device such as a sheath covering the valve. When
`the valve is positioned at or near the target site, the restraining
`device is removed to allow the valve to self-expand to its
`expanded, functional size.
`[0056] Referring also to FIG. 3 (which shows the frame
`alone for purposes of illustration), the frame 52 is a generally
`tubular, stent-like structure having a plurality of angularly
`
`spaced, vertically extending struts, or commissure attach-
`ment posts 64. The reader will note that the posts 64 in FIG.
`3 are somewhat modified from those shown in FIG. 2, the
`differences being minimal. The posts 64 are interconnected
`via several rows of circumferentially extending struts 66.
`Thinner vertical (axial) struts 68 intermediate the commis-
`sure attachment posts 64 connect to and extend between
`adjacent horizontal rows of struts 66. The struts in each row
`are desirably arranged in a zigzag or generally saw-tooth
`pattern extending in the direction of the circumference of the
`frame as shown. Adjacent struts in the same row can be
`interconnected to one another as shown to form an angle
`when expanded, desirably between about 90 and 1 10 degrees.
`This optimizes the radial strength offrame 52 when expanded
`yet still permits the frame 52 to be evenly crimped and then
`expanded in the manner described below.
`[0057] Leaflet structure 54 desirably comprises three sepa-
`rate connected leaflets 70 such as shown in FIG. 4, which can
`be arranged to collapse in a tricuspid arrangement, as best
`shown in FIGS. 2 and 5. Each leaflet 70 has a curved lower
`
`cusp edge 72 opposite a generally straight upper free edge 74,
`and two commissure flaps 76 extending between the free edge
`74 and the lower edge 72. The curved cusp edge 72 forms a
`single scallop in the leaflet structure 54. When secured to two
`other leaflets 70 to form the leaflet structure 54, the curved
`cusp edges 72 of the leaflets collectively form a scallop-
`shaped lower edge of the leaflet structure (as best shown in
`FIG. 5). As further shown in FIG. 4, two reinforcing bars 78
`can be secured to each leaflet 70 adjacent to flaps 76 (e.g.,
`using sutures). The flaps can then be folded over bars 78 and
`secured in the folded position using sutures. If desired, each
`bar 78 can be placed in a protective sleeve (e.g., a PET sleeve)
`before being secured to a leaflet.
`[0058] Leaflets 70 attach to one another at their adjacent
`sides to form commissures 80 ofthe leaflet structure (see FIG.
`2 at the edges where the leaflets come together). Leaflet
`structure 54 can be secured to frame 52 using various tech-
`niques and mechanisms. For example, as best shown in FIG.
`2, commissures 80 of the leaflet structure desirably are
`aligned with the support posts 64 and secured thereto using
`sutures through holes 82 (FIG. 3). The point of attachment of
`the leaflets to the posts 64 can be reinforced with the bars 78
`(FIG. 4), which desirably are made of a relatively rigid mate-
`rial (compared to the leaflets), such as stainless steel.
`[0059] As mentioned, the lower edge of leaflet structure 54
`desirably has an undulating, curved scalloped shape. A suture
`line 84 visible on the exterior of the skirt 56 in FIG. 2 tracks
`
`the scalloped shape ofthe leaflet structure 54. By forming the
`leaflets with this scalloped geometry, stresses on the leaflets
`are reduced, which in turn improves durability of the valve.
`Moreover, by virtue of the scalloped shape, folds and ripples
`at the belly of each leaflet (the central region of each leaflet),
`which can cause early calcification in those areas, can be
`eliminated or at least minimized. The scalloped geometry
`also reduces the amount oftissue material used to form leaflet
`
`structure, thereby allowing a smaller, more even crimped
`profile at the inflow end of the valve.
`[0060] Referring again to FIGS. 2 and 5, the skirt 56 can be
`formed, for example, of polyethylene terephthalate (PET)
`ribbon. The leaflet structure 54 attaches to the skirt via a thin
`
`PET reinforcing strip 88 (or sleeve), FIG. 5, which enables a
`secure suturing and protects the pericardial tissue of the leaf-
`let structure from tears. The leaflet structure 54 is sandwiched
`
`between skirt 56 and the reinforcing strip 88. The suture 84,
`
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`US 2013/0310929 A1
`
`Nov. 21,2013
`
`which secures the reinforcing strip and the leaflet structure 54
`to skirt 56 can be any suitable suture, and desirably tracks the
`curvature of the bottom edge of leaflet structure 54, as see on
`the exterior of the skirt 56 in FIG. 2. The skirt 56 and leaflet
`
`structure 54 assembly resides inside of frame 52 and secures
`to the horizontal struts 66 Via a series of zigzag pattern sutures
`86, as shown in FIG. 2.
`[0061]
`To assemble, the heart valve leaflets 7