(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`(19) World Intellectual Property
`Organization
`International Bureau
`
`(43) International Publication Date
`6 August 2015 (06.08.2015)
`
`P O P C T
`
`(10) International Publication Number
`WO 2015/116917 Al
`
`(51) International Patent Classification:
`A61K 38/39 (2006.01)
`A61F 13/00 (2006.01)
`
`(21) International Application Number:
`
`(22) International Filing Date:
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`PCT/US2015/013732
`
`30 January 2015 (30.01 .2015)
`
`English
`
`English
`
`(30) Priority Data:
`61/933,578
`
`30 January 2014 (30.01.2014)
`
`US
`
`(71) Applicant: POLY-MED, INC. [US/US]; 5 1 Technology
`Drive, Anderson, SC 29625 (US).
`
`BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM,
`DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT,
`HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR,
`KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG,
`MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM,
`PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC,
`SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN,
`TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
`
`(84) Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ,
`TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU,
`TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE,
`DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU,
`LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK,
`SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,
`GW, KM, ML, MR, NE, SN, TD, TG).
`
`(72) Inventors: TAYLOR, Michael, Scott; 214 Andalusian
`Trail, Anderson, SC 29621 (US). MCCULLEN, Seth,
`Dylan; 2107 East North Street, Greenville, SC 29607 Declarations under Rule 4.17 :
`(US). SHALABY, David; 1093 Clayton Mill Road, South- — as to applicant's entitlement to apply for and be granted a
`field, MA 01259 (US).
`patent (Rule 4.1 7(H))
`(74) Agent: LAHEY, Seann; Mcnair Law Firm, P.A., P.O. Box — as to the applicant's entitlement to claim the priority of the
`447, Greenville, SC 29602-0447 (US).
`earlier application (Rule 4.1 7(in))
`(81) Designated States (unless otherwise indicated, for every — of inventorship (Rule 4.17(iv))
`kind of national protection available): AE, AG, AL, AM,
`AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY,
`
`(54) Title: TIME-DEPENDENT SYNTHETIC BIOLOGICAL BARRIER MATERIAL
`
`[Continued on next page]
`
`FIG. 1
`
`(57) Abstract: Thermally stable absorbable fiber populations,
`i.e. fiber populations that do not undergo thermally induced crystalliz -
`ation, can be intermixed to yield a stabilizing effect without altering morphological properties of a first fiber system. By addition of a
`stabilizing fiber population one may minimize thermally induced shrinkage and maintain physical properties of electrospun materials
`in the as-formed state. In one particular abstract, medical barrier materials may be formed from the electrospun materials to provide
`improved medical barriers for treatments.
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`WO 2015/116917 Al III III IIII II I IIII
`
`Published:
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`TIME-DEPENDENT SYNTHETIC BIOLOGICAL BARRIER MATERIAL
`
`BACKGROUND OF THE INVENTION
`
`[0001]
`
`Fibrous materials are capable of providing a barrier for a range of
`
`membrane applications including:
`
`tissue separation, hernia repair, peritoneum
`
`replacement, dura mater replacement, and pelvic floor reconstruction, amongst
`
`others. Of these types of tissue replacement, hernia repair is one of the most
`
`frequently performed surgical operations in the United States with approximately
`
`one million procedures conducted annually.
`
`[0002]
`
`The vast majority of these membrane applications,
`
`including hernia
`
`repairs, employ synthetic surgical meshes that are comprised of various
`
`arrangements of absorbable and non-absorbable films, fibers, and yarns, and are
`
`primarily based on traditional knit and woven structures. These materials have
`
`reduced the frequency of hernia recurrence. Unfortunately,
`
`recurrence rates
`
`remain high, with up to 15% recurrence reported for inguinal and incisional hernia
`
`repair.
`
`[0003]
`
`In addition, long-term complications such as chronic pain, increased
`
`abdominal wall stiffness, fibrosis, and mesh contraction persist following the use
`
`of current surgical meshes.
`
`These complications dramatically affect patient
`
`quality of life. To counteract these complications, medical device technology has
`
`moved toward development of synthetic repair meshes consisting of 100%
`
`absorbable materials. To date, no significant clinical data is available to
`
`determine the viability of such absorbable meshes.
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`[0004]
`
`A benefit of absorbable meshes is that they would not need to be
`
`removed following surgery and do not disrupt new tissue formation of collagen
`
`upon healing. However, preliminary studies with completely absorbable hernia
`
`meshes indicate that
`
`the replacement collagen layer is not strong enough to
`
`prevent hernia recurrence and often results in catastrophic failure. This is most
`
`likely due to the relatively fast degradation profile of meshes such as VICRYL
`
`knitted mesh, available from Ethicon Inc., a subsidiary of Johnson and Johnson.
`
`These meshes degrade in approximately three to four weeks. However,
`
`the
`
`collagen remodeling process may take several months for it to mature and gain
`
`normal or pre-injury strength.
`
`[0005]
`
`Synthetic barrier materials such as hernia meshes are largely
`
`comprised of nondegradable fibrous arrays constructed from either knitted,
`
`woven, or nonwoven methodologies. Recently, the electrospinning method has
`
`generated significant
`
`interest
`
`in medical device applications. The process can
`
`produce micro-fibrous materials with a topography and size-scale similar to the
`
`native extracellular matrix. Electrospun materials are advantageous for a range
`
`of applications in the medical device field for tissue replacement, augmentation,
`
`drug delivery, among other applications.
`
`[0006]
`
`During the electrospinning process, a polymer
`
`is dissolved in
`
`solution and is metered at a controlled flow rate through a capillary or orifice. By
`
`applying a critical voltage to overcome the surface tension of
`
`the polymer
`
`solution, along with sufficient molecular chain entanglement
`
`in solution,
`
`fiber
`
`formation can occur. Application of a critical voltage induces a high charge
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`density
`
`forming a Taylor
`
`cone,
`
`the cone observed
`
`in electrospinning,
`
`electrospraying and hydrodynamic spray processes, from which a jet of charged
`
`particles emanates above a threshold voltage, at the tip of the orifice.
`
`[0007]
`
`Emerging from the Taylor cone, a rapid whipping instability, or fiber
`
`jet,
`
`is formed moving at approximately 10 m/s from the orifice to a distanced
`
`collector. Due to the high velocity of the fiber jet, fiber formation occurs on the
`
`order of milliseconds due to the rapid evaporation of the solvent (i.e., solution
`
`electrospinning),
`
`inhibiting polymer crystallization. Typically, the ejected jets from
`
`the polymer solution is elongated more than 10,000 draw ratio in a time period of
`
`0.05s. This high elongation ratio is driven by the electric force induced whipping
`
`instability, and the polymer chains remain in an elongated state after
`
`fiber
`
`solidification due to this high elongation and chain confinement within micron-
`
`sized fibers.
`
`[0008]
`
`For semi-crystalline polymers,
`
`retarded crystallization may be
`
`observed as fast solidification of the stretched polymer chains do not allow time
`
`to organize into suitable crystal registration, and is also inhibited by the small
`
`fiber diameters.
`
`The formation process may impart a significant amount of
`
`internal stresses into the resulting fibers. As a result,
`
`these materials can
`
`undergo both morphological and mechanical property changes when exposed to
`
`heat due to cold crystallization as well as stress relief via application of heat.
`
`Polymers that display a glass transition temperature (Tg) near or at body
`
`temperature
`
`(37°C) are unstable for biological applications
`
`due to the
`
`uncontrolled transition between a glassy and amorphous state. Exposing
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`temperature sensitive materials to temperatures near or at their Tg ultimately
`
`yields crystallization events which have both micro and macroscopic effects on
`
`electrospun fabrics.
`
`[0009]
`
`Electrospun materials may be relatively unstable and may undergo
`
`crystallization due to their amorphous nature and highly elongated polymer
`
`chains residing within their polymeric fibers. Further, residual stresses may be
`
`generated from the dynamic "whipping" process used to produce small-diameter
`
`fibers. As typical electrospun materials undergo thermal
`
`treatments/exposure,
`
`polymer crystallization can occur, distorting fiber topography, pore size, inducing
`
`shrinkage and altering mechanical properties.
`
`For
`
`instance,
`
`in the case of
`
`poly(lactic-co-glycolic) acid ("PGLA") copolymers, such as VICRYL 90/1 0 PGLA,
`
`at temperatures of 37°C, shrinkage as high as 20% has been observed. This
`
`results in smaller constructs with significantly higher stiffness as well as loss of
`
`desirable chemical and mechanical properties.
`
`[0010]
`
`What
`
`is needed in the art are improved medical devices, such as
`
`synthetic barrier materials,
`
`including but not
`
`limited to membrane applications
`
`including:
`
`tissue separation, hernia repair, peritoneum replacement, dura mater
`
`replacement, and pelvic floor reconstruction,
`
`incorporating electrospun materials
`
`that exhibit both structural and thermal stability without
`
`requiring additional
`
`processing or treatment once the fiber web or mesh is formed. The following
`
`disclosure addresses this need.
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`SUMMARY OF THE INVENTION
`
`[001 1]
`
`The present disclosure is directed toward generating synthetic
`
`barrier materials,
`
`including but not
`
`limited to membrane applications such as:
`
`tissue
`
`separation,
`
`hernia
`
`repair,
`
`peritoneum replacement,
`
`dura mater
`
`replacement, and pelvic floor reconstruction materials. These barrier materials
`
`offer temporal properties and functions and employ multiple fiber populations of
`
`materials including an absorbable and non-absorbable (i.e. non-degradable)
`
`material
`
`to generate a tailored mechanical behavior characteristic of
`
`the
`
`abdominal wall and/or tissue for replacement.
`
`[0012]
`
`Nonwoven fibrous arrays are useful
`
`in the present disclosure due to
`
`their topography and size-scale, both of which mimic the extracellular matrix and
`
`offer enhanced functionality. Nonwoven materials can be produced through a
`
`variety of solution spinning applications, as known to those of skill
`
`in the art,
`
`including but not limited to electrospinning and wet-spinning.
`
`[0013]
`
`With respect
`
`to the current disclosure, electrospinning produces
`
`fibrous materials by driving high elongational whipping of polymer solutions/melts
`
`as a means to extend the polymer
`
`reservoir
`
`into a fiber.
`
`Separate fiber
`
`populations may be used that have different morphology,
`
`topography, and
`
`mechanics, wherein one population provides initial strength upon implantation at
`
`the defect site while the second population contributes to long term elasticity and
`
`provides
`
`a permanent
`
`scaffolding
`
`barrier
`
`for
`
`tissue
`
`reconstruction
`
`and
`
`regeneration.
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`[0014]
`
`The present disclosure may utilize electrospun barriers, webs or
`
`fabrics and may rely on their use as a dynamic barrier material. This, coupled
`
`with at least one absorbable polymer and at least one nonabsorbable polymer,
`
`provides a barrier material system that exhibits modularity in strength, modulus
`
`(stiffness), and porosity. The current disclosure may also provide carriers for
`
`biologically active agents, while providing a dimensionally and thermally-
`
`stabilized construct, especially given the required temperature
`
`conditions
`
`including the biologically relevant 37°C, as well as 50 °C which is needed for shelf
`
`stability and sterilization processing.
`
`[0015]
`
`Electrospun materials are of great interest for medical applications,
`
`but are limited based on their instability. What
`
`is needed are thermally stable
`
`absorbable or non-absorbable
`
`electrospun materials with little or
`
`limited
`
`macroscopic changes in physical and mechanical properties when exposed to
`
`thermal, mechanical, or other stresses. As the present disclosure explains, this
`
`may be realized through forming a barrier material
`
`that employs at
`
`least
`
`two
`
`independent
`
`fiber populations with a major fiber component comprising at least
`
`one thermally unstable species and a minor fiber component comprising at least
`
`one thermally stable species which are co-mingled and distributed throughout.
`
`[0016]
`
`Further,
`
`the disclosed electrospun materials would not
`
`rely on
`
`downstream chemical processing or complex layered or fiber blend approaches,
`
`as known in the art, and would be superior to current technologies that employ
`
`layered constructs, cross-linked constructs, and/or creating nonwoven constructs
`
`with a core/sheath or blended fiber. Current
`
`technologies create increased
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`production complexity due to the need for specialized equipment and cross-
`
`linking requires additional processing, such as exposure to ultraviolet
`
`light, and
`
`the introduction of additional chemical compounds that could be detrimental
`
`to
`
`product biocompatibility. The current disclosures rectifies these shortcomings.
`
`[0017]
`
`Indeed,
`
`the current disclosure may be used to form layered,
`
`core/sheath, and/or blended fibers. One benefit of employing these constructs
`
`would be tissue ingrowth due to the presence of degradable laminates adjacent
`
`to intermixed population of bulk material. Even further, articulated surfaces may
`
`be produced wherein an aligned fiber surface is formed in contrast to a randomly
`
`aligned surface. However, randomly aligned fibers, as opposed to aligned fibers,
`
`may be used to form an adhesion surface.
`
`[0018]
`
`In one embodiment, a thermally stable electrospun barrier may be
`
`provided. The barrier may exhibit limited macroscopic changes in physical and
`
`mechanical properties when exposed to thermal, mechanical, or other stresses.
`
`The electrospun barrier may include at least two independent
`
`fiber populations
`
`with a major fiber component comprising at least one thermally unstable species
`
`and a minor fiber component comprising at least one thermally stable species.
`
`The major and minor fiber components may be co-mingled and distributed
`
`throughout
`
`the electrospun barrier. Further,
`
`the electrospun material
`
`forms at
`
`least a portion of an implantable material.
`
`[0019]
`
`In a further embodiment,
`
`the major
`
`fiber population may be
`
`nonabsorbable.
`
`In a yet
`
`further embodiment,
`
`the minor fiber population is
`
`absorbable.
`
`In a still yet further embodiment, the minor fiber population may be
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`nonabsorbable.
`
`Still
`
`further,
`
`the minor fiber may have a higher crystallization
`
`temperature than the major fiber.
`
`In another embodiment,
`
`the minor fiber may
`
`have a lower crystallization temperature than the minor fiber. Yet still further, the
`
`major fiber population may have a crystallization temperature in the range of 50
`
`to 80 C and the minor fiber population may have a crystallization temperature in
`
`the range of 100-1 40 C . Even further, porosity of the barrier may be 75% or
`
`greater.
`
`Further
`
`still,
`
`the thermally
`
`stable electrospun
`
`barrier may be
`
`dimensionally stable over a range of temperatures from 30 C to 60 C and will
`
`not decrease in size by more than 10 percent.
`
`In a further embodiment, porosity
`
`of
`
`the thermally stable electrospun barrier may increase as the major
`
`fiber
`
`population is absorbed. Still further,
`
`the major fiber population may be derived
`
`from cyclic monomers selected from the group consisting of glycolide,
`
`lactide,
`
`caprolactone, para-dioxanone,
`
`trimethylene carbonate or mixtures thereof. Still
`
`further,
`
`the major fiber population may experience decreases in area weight or
`
`area density as it
`
`is absorbed. As the major fiber population is absorbed,
`
`the
`
`resulting fabric may have a lower area density/area weight.
`
`Ultimately,
`
`the
`
`construct may be stable and the density may be reduced by the percentage of
`
`the fast-absorbing major fabric population.
`
`[0020]
`
`In a further embodiment,
`
`the major fiber population may be any
`
`polymer that
`
`is degradable by hydrolysis or other biodegradation mechanisms.
`
`Still further,
`
`the major fiber population may be trimethylene carbonate,
`
`lactide,
`
`glycolide,
`
`e -caprolactone, para-dioxanone or mixtures of the above.
`
`In a still
`
`further embodiment,
`
`the major fiber population may be an absorbable PGLA
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`copolymer with a monomer ratio of 90:1 0 . Yet further, the minor fiber population
`
`may be a polyether-ester.
`
`In still another embodiment,
`
`the minor fiber population
`
`may be a block copolymer having one or more blocks of polydioxanone. Yet
`
`even further, polydioxanone may comprise from 10% to 80% of the copolymer.
`
`In another embodiment,
`
`the minor fiber population may be nonabsorbable and
`
`may further be poly(ethylene terephthalate).
`
`In a further embodiment,
`
`the minor
`
`fiber population may be a copolymer and the nonabsorbable fiber comprises from
`
`10% to 80% of the copolymer.
`
`[0021]
`
`In a still yet further embodiment, a method of forming a thermally
`
`stable electrospun is disclosed. The method may include dissolving a major fiber
`
`population in a solvent and dissolving a minor fiber population in a solvent. The
`
`dissolved major and minor fiber populations may be electrospun to form a co-
`
`spun barrier with the dissolved major and minor fiber populations dispensed
`
`through an alternating needle sequence to form an intermixed structure
`
`comprised of the major and minor fiber populations.
`
`[0022]
`
`In a further embodiment,
`
`the major
`
`fiber population may be
`
`bioabsorbable copolymer of glycolic and lactic acid. Still further,
`
`the minor fiber
`
`population may be a bioabsorbable block copolymer having one or more blocks
`
`of polydioxanone. Even further, the barrier may be formed into a surgical mesh.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0023]
`
`The construction designed to carry out the invention will hereinafter
`
`be described,
`
`together with other features thereof. The invention will be more
`
`readily understood from a reading of the following specification and by reference
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`to the accompanying drawings forming a part thereof, wherein an example of the
`
`invention is shown and wherein:
`
`[0024]
`
`[0025]
`
`Figure 1 is a schematic view of an electrospinning process;
`
`Figure 2 shows an electron microscope view of 90/1 0 PGLA fibers
`
`after exposure to 45 C for 30 minutes; and
`
`[0026]
`
`Figure 3 shows an electron microscope view of 90/1 0 PGLA plus
`
`PDO cospun fibers after exposure to 45 C for 30 minutes.
`
`[0027]
`
`patch.
`
`[0028]
`
`Figure 4 depicts an example of a conventional prior art hernia
`
`Figure 5 shows an electron microscopy image of a PGLA fiber
`
`network without PPD.
`
`[0029]
`
`Figure 6 shows an electron microscopy image of PGLA with PPD at
`
`a 2:1 ratio.
`
`[0030]
`
`Figure 7 shows an electron microscopy image of PGLA after being
`
`exposed to 50 C .
`
`[0031]
`
`Figure 8 shows an electron microscopy image of a PGLA/PPD
`
`composite with a 2:1 ratio after being exposed to 50 C .
`
`[0032]
`
`Figure 9 demonstrates an electrospun construct of
`
`the present
`
`disclosure made at room temperature.
`
`[0033]
`
`Figure 10 demonstrates an electrospun construct of
`
`the present
`
`disclosure formed at -80 C .
`
`[0034]
`
`It will be understood by those skilled in the art that one or more
`
`aspects of this invention can meet certain objectives, while one or more other
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`aspects can meet certain other objectives. Each objective may not apply equally,
`
`in all
`
`its respects,
`
`to every aspect of
`
`this invention. As such,
`
`the preceding
`
`objects can be viewed in the alternative with respect
`
`to any one aspect of this
`
`invention. These and other objects and features of the invention will become
`
`more fully apparent when the following detailed description is read in conjunction
`
`with the accompanying figures and examples. However,
`
`it
`
`is to be understood
`
`that both the foregoing summary of
`
`the invention and the following detailed
`
`description are of a preferred embodiment and not restrictive of the invention or
`
`other alternate embodiments of the invention.
`
`In particular, while the invention is
`
`described herein with reference to a number of specific embodiments,
`
`it will be
`
`appreciated that
`
`the description is illustrative of
`
`the invention and is not
`
`constructed as limiting of the invention. Various modifications and applications
`
`may occur to those who are skilled in the art, without departing from the spirit and
`
`the scope of the invention, as described by the appended claims. Likewise, other
`
`objects,
`
`features, benefits and advantages of
`
`the present
`
`invention will be
`
`apparent from this summary and certain embodiments described below, and will
`
`be readily apparent to those skilled in the art. Such objects, features, benefits and
`
`advantages will
`
`be apparent
`
`from the above
`
`in
`
`conjunction with the
`
`accompanying examples, data, figures and all reasonable inferences to be drawn
`
`therefrom, alone or with consideration of the references incorporated herein.
`
`DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
`
`[0035]
`
`With reference to the drawings, the invention will now be described
`
`in more detail. Unless defined otherwise, all technical and scientific terms used
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`herein have the same meaning as commonly understood to one of ordinary skill
`
`in the art to which the presently disclosed subject matter belongs. Although any
`
`methods, devices, and materials similar or equivalent
`
`to those described herein
`
`can be used in the practice or testing of the presently disclosed subject matter,
`
`representative methods, devices, and materials are herein described.
`
`[0036]
`
`The barrier material of the present disclosure comprises at least two
`
`separate fiber populations wherein the primary or major
`
`fiber population is
`
`absorbable and provides high strength in terms of tensile strength and modulus.
`
`The primary fiber population also provides desired handling properties as it will
`
`typically comprise the bulk of the barrier, fabric or mesh.
`
`[0037]
`
`The secondary or minor
`
`fiber population is nondegradable or
`
`nonabsorbable and provides permanent scaffolding that will remain essentially
`
`unchanged for the lifetime of the patient
`
`following absorption of the first
`
`fiber
`
`population. The secondary fiber populations may provide enhanced elasticity
`
`compared to that of the bulk device and enhanced elasticity compared to the first
`
`fiber population. Additionally,
`
`in the case wherein the second fiber population
`
`consists predominantly or entirely of polyethylene terephthalate,
`
`the second fiber
`
`population may provide a stabilizing effect by having a higher crystallization
`
`temperature comparative to the first fiber population with ranges of 50-80 °C for
`
`the first fiber population and 100-1 40 °C for the second fiber population.
`
`In other
`
`cases where
`
`a different
`
`non-absorbable
`
`fiber,
`
`such
`
`as
`
`polyethylene,
`
`polypropylene or a form of Nylon,
`
`is used for
`
`the second stabilizing fiber
`
`population,
`
`the crystallization temperature range may be different
`
`than that
`
`for
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`polyethylene terephthalate. The inclusion of the secondary fiber population may
`
`provide a stabilizing effect. This effect is unexpected due to the "stabilizing" fibers
`
`providing long range stability (overall barrier dimensions) as well as short range
`
`(individual unstable fiber elements that are not necessarily bound by the other
`
`stabilizing fibers) stability.
`
`[0038]
`
`Macroscopically,
`
`typical electrospun fibers can become distorted
`
`with a change in morphology resulting in a change in barrier pore size and
`
`handling.
`
`To overcome
`
`this
`
`limitation
`
`and minimize
`
`such
`
`changes,
`
`nondegradable fiber populations with a high Tg, ranging from 55 °C to 100°C or
`
`greater than 100°C can be incorporated into the barrier, when electrospun,
`
`to
`
`minimize the macroscopic effects of
`
`thermally induced crystallization to the
`
`primary absorbable fiber population. By adding a secondary fiber population, one
`
`may impart unique properties that
`
`include preferable mechanical, drape and
`
`handing properties, minimize thermally induced shrinkage, and maintain physical
`
`properties of electrospun materials in the as-formed state for in vivo application.
`
`[0039]
`
`The present disclosure differs from other concepts to improve
`
`dimensional and thermal stability. These concepts include ( 1 ) layered fabrics, (2)
`
`cross-linking, and (3) composite fibers wherein the individual
`
`fiber comprises
`
`nonstable and stabilizing elements. Moreover,
`
`the current disclosure may
`
`provide a barrier, mesh, web, or fabric that is not comprised of an electrospun
`
`nonwoven layer deposited on top of a knit/woven structure.
`
`Instead, the current
`
`disclosure may provide an electrospun nonwoven construct
`
`that provides the
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`totality of mechanical functionality without the need for incorporating an additional
`
`knit or woven structure.
`
`[0040]
`
`It is important to note that the disclosed barrier, mesh, web or fabric
`
`can be produced in a 1-step process, as opposed to multi-step layering
`
`processes and complex knitting and weaving processes.
`
`It
`
`is also unusual that
`
`the electrospun construct itself is used as the mechanical component, whereas it
`
`is typically used by those of skill
`
`in the art as a coating or barrier
`
`layer
`
`in
`
`association with woven or other formed articles. Furthermore,
`
`the modulation of
`
`porosity and extensibility/modulus based on the degradation of the absorbable
`
`component
`
`is also unique in the literature. Porosity can be modulated from 75%
`
`or higher with pore sizes ranging from 1 to 300 m
`
`2. Extensibility of the barrier
`
`material can range from 0 to 20% for some applications, or much greater
`
`extensibility for other applications,
`
`i.e. up to 500% strain at break. For instance,
`
`extensibility may range from 20% to 100%, 50% to 100%, 100% to 200%, 150%
`
`to 200%, 200% to 300%, 250% to 300%, 300% to 400%, 350% to 400%, 400%
`
`to 500%, and from 450% to 500% including combinations of the aforementioned
`
`ranges, including but not limited to subsets of same.
`
`[0041]
`
`In one particular embodiment,
`
`the barrier, mesh or fabric of
`
`the
`
`present disclosure comprises intermingled, small-diameter with a range of 0.1 to
`
`20 miti
`
`, with a more preferable range of 0.5 to 10 miti
`
`, non-woven fibers
`
`comprised of at
`
`least
`
`two independent
`
`fiber populations, although more fiber
`
`populations such as three,
`
`four,
`
`five, six, etc., may be possible and are
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`contemplated by the disclosure. Of the independent
`
`fiber populations, at least
`
`one fiber type is absorbable and at least one fiber type is non-absorbable.
`
`[0042]
`
`In another embodiment,
`
`the barrier is dimensionally stable over a
`
`range of temperatures such as from about 30 C to about 60 °C.
`
`In a further
`
`embodiment,
`
`the barrier is dimensionally stable over the range of 35 C to 60 C .
`
`The term "dimensionally stable" is used herein to connote that the dimensions of
`
`the barrier upon completion of formation will not change or decrease in size by
`
`more than ten percent, five percent,
`
`in some cases three percent, and in some
`
`cases not more than one percent once introduced into the patient.
`
`In another
`
`embodiment
`
`the barrier may be dimensionally stable on the microscopic level,
`
`wherein the fibers that constitute the barrier do not alter in morphology upon
`
`exposure to temperatures from 35 °C to 60 °C.
`
`It
`
`is believed that by the barrier
`
`being nonwoven and containing at least one fiber population with a relatively high
`
`crystallization temperature (Tc)
`
`that
`
`this dimensionally stabilizes the barrier
`
`construct.
`
`[0043]
`
`In a further embodiment,
`
`the barrier of the current disclosure may
`
`be produced as a nonwoven product
`
`in a 1-step process.
`
`In one preferred
`
`embodiment,
`
`the barrier may be formed as a nonwoven
`
`product
`
`via
`
`electrospinning wherein the major and minor fiber populations are employed to
`
`make a nonwoven "mat" of a desired thickness that may then be cut or otherwise
`
`formed into desired shapes and sizes.
`
`One step manufacturing can be
`
`accomplished by dispensing different
`
`fibers from separate spinnerets onto the
`
`same collector. The produced material can be of any size or shape required to
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`treat a tissue defect.
`
`For
`
`instance, dimensions for a hernia mesh with
`
`dimensions ranging from about 1" x 3" to about 5" x 7" are possible.
`
`In one
`
`embodiment, the strength of the resulting materials would have an initial strength
`
`of about 16 N/cm at between about 18-32% extension for a hernia application
`
`structure.
`
`[0044]
`
`In a further embodiment,
`
`the barrier may exhibit an initial relatively
`
`high modulus/low elasticity as compared to native tissue,
`
`i.e., the tissue in the
`
`region or area where the barrier is to be introduced for use. Over time the
`
`elasticity for the barrier material can be less than 10% with a graded increase in
`
`elasticity over a period of 4 to 128 weeks,
`
`the barrier transitions to a relatively
`
`extensible material as compared to native tissue exhibiting extensibility in the
`
`range of 20% or higher as compared to the surrounding tissue.
`
`[0045]
`
`In a further embodiment,
`
`the structure of
`
`the barrier may be
`
`designed to initially inhibit
`
`tissue ingrowth altogether or provide for low initial
`
`tissue ingrowth.
`
`In a further embodiment, barrier materials exhibit an initial pore
`
`size in the range of 1 to 20 miti
`
`or less for the first
`
`four weeks.
`
`Following
`
`degradation of the absorbable component the pore size increases from 20 miti
`
`to
`
`100 to 300 miti
`
`dependent on ratios of the separate fiber populations.
`
`One way
`
`this may be accomplished is by controlling the porosity of the barrier by varying
`
`the ratio of the fiber populations through the thickness of the material, having a
`
`majority of the absorbable component on one side of the material with minimal
`
`nondegradable fibers and a gradual
`
`increase in nondegradable fibers throughout
`
`the thickness. As the major component degrades, the porosity of the barrier may
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`NANOFIBER 1016
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`increase up to a final porosity level that remains when the major component
`
`is
`
`completely degraded leaving only the minor component and its porosity. The
`
`differences between these porosities may range from 10 to 95%.
`
`[0046]
`
`One embodiment of
`
`the disclosure provides that
`
`the barrier
`
`is
`
`relatively compliant and extensible after first component degrades. Degradation
`
`of the major component may be designed into the barrier based on the amount of
`
`the major component used, type of fiber used as the major component as well as
`
`combinations of
`
`these two factors.
`
`Examples of
`
`the major component can
`
`include the copolymer PGLA and the minor component can include poly(ethylene
`
`terephthalate).
`
`In one embodiment a fast degrading composition may be formed
`
`that
`
`is 90:1 0 PGLA or a slow degrading composition may be used that may be
`
`88:1 2 Poly(lactide-co-TMC) or PLA. Ranges of polymer ratios are also within the
`
`scope of this disclosure such as 95:5, 85:1 5 , 80:20, 75:25, 70:30, 65:35, 60:40,
`
`55:45, and 50:50, as well as measurements within these ranges such as 89:1 1,
`
`87:1 3 , or ranges covering 95:5 to 85:1 5 , etc. Other composition mixtures are
`
`envisioned by this disclosure and may include polymers comprised of glycolide,
`
`lactide, caprolactone,
`
`trimethylene carbonate, para dioxanone and mixtures of
`
`the above. Degradation may be selected to occur over a range of weeks, such
`
`as degrading from two to sixteen weeks. For instance,
`
`in a further embodiment,
`
`different barriers may be designed so that one barrier has a major component
`
`that
`
`is completely degraded within two weeks whereas another formulation may
`
`have a major component
`
`that degrades within sixteen weeks.
`
`The major
`
`co