Abstract:
A flexible anchor for coupling a suture to a bone is provided. The anchor is composed of non-woven electrospun fibers and has an elongate tubular body that extends from a first end to a second end. The anchor is configured to receive a suture that enters the anchor through a first aperture and exits the anchor through a second aperture. When free ends of the suture are pulled, the anchor transitions from a first configuration to a second anchoring configuration

Description:
FIELD 
       [0001]    The present disclosure relates generally to an apparatus for anchoring a suture to a bone. 
       BACKGROUND 
       [0002]    This section provides background information related to the present disclosure which is not necessarily prior art. 
         [0003]    It is commonplace in arthroscopic procedures to employ sutures and anchors to secure soft tissues to bone. Various commercially available “soft” anchors include a coreless sleeve of woven (braided) polyester, such as polyethylene terephthalate (PET). Such polyester sleeves serve as an anchor by bunching up against cortical bone when a suture threaded through the sleeve is pulled tight through a hole drilled into the bone. 
         [0004]    While woven or braided polyester sleeves provide mechanical anchoring strength in the immediate time following surgery, they generally do not invite biological fixation to further stabilize the soft anchor inside of the bone. Woven or braided polyester sleeves do not encourage tissue infiltration and integration because, PEP, as with polymers in general, is hydrophobic, which does not enable cellular or tissue attachment. Additionally, the size of polyester filaments is much larger than the size of cells, which causes the filaments to be viewed as foreign bodies by cells and by the immune system. Accordingly, there remains a need to develop anchors that encourage cellular ingrowth and biological fixation to bone. 
       SUMMARY 
       [0005]    This section provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features. 
         [0006]    The present technology provides an anchor for coupling a suture to a bone. The anchor is composed of a non-woven material and includes an elongate tubular body that extends from a first end to a second end. The anchor is configured to receive a suture that enters the anchor through a first aperture and exits the anchor through a second aperture. Pulling free ends of the suture sets the anchor in an anchoring configuration when the anchor is inserted in a bore in a bone. The non-woven material includes electrospun fibers. 
         [0007]    The present technology also provides an anchor for coupling a suture to a bone. The anchor has a solid or hollow elongate tubular body extending from a first end to a second end. The anchor is composed of non-woven electrospun fibers. The non-woven electrospun fibers include at least one modifying agent, at least one biological agent, or at least one antimicrobial agent. The tubular body can be hollow, such that it defines an internal passage, or the tubular body can be solid. 
         [0008]    Additionally, the present technology provides a suture assembly that includes a flexible anchor and a suture that has a first free end and a second free end. The flexible anchor has an elongate tubular body that extends from a first end to a second end. The flexible anchor is of non-woven electrospun fibers. The suture is passed into the flexible anchor through a first opening and is passed out of the flexible anchor through a second opening, such that the first and second free ends of the suture are external to the flexible anchor. The suture assembly is configured to switch from a first configuration to a second locking configuration when the anchor is inserted into a bore prepared in a bone and the free ends are pulled in a direction that is generally coaxial with and away from bore. 
         [0009]    Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. 
     
    
     
       DRAWINGS 
         [0010]    The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure. 
           [0011]      FIG. 1  is a schematic illustration of a suture assembly according to the present technology; 
           [0012]      FIG. 1A  is an exploded view of a portion of the suture assembly shown in  FIG. 1 ; 
           [0013]      FIG. 2  is a schematic illustration of the suture assembly placed in a bore prepared in a bone, wherein the suture assembly is in a first configuration; and 
           [0014]      FIG. 3  is a schematic illustration of the suture assembly placed in a bore prepared in a bone, wherein the suture assembly is in a second configuration. 
       
    
    
       [0015]    Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings. 
       DETAILED DESCRIPTION 
       [0016]    Example embodiments will now be described more fully with reference to the accompanying drawings. 
         [0017]    The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms “comprises,” “comprising,” “including,” and “having,” are inclusive and therefore specify the presence of stated features, elements, compositions, steps, integers, operations, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. Although the open-ended term “comprising,” is to be understood as a non-restrictive term used to describe and claim various embodiments set forth herein, in certain aspects, the term may alternatively be understood to instead be a more limiting and restrictive term, such as “consisting of” or “consisting essentially of.” Thus, for any given embodiment reciting compositions, materials, components, elements, features, integers, operations, and/or process steps, the present disclosure also specifically includes embodiments consisting of, or consisting essentially of, such recited compositions, materials, components, elements, features, integers, operations, and/or process steps. In the case of “consisting of,” the alternative embodiment excludes any additional compositions, materials, components, elements, features, integers, operations, and/or process steps, while in the case of “consisting essentially of,” any additional compositions, materials, components, elements, features, integers, operations, and/or process steps that materially affect the basic and novel characteristics are excluded from such an embodiment, but any compositions, materials, components, elements, features, integers, operations, and/or process steps that do not materially affect the basic and novel characteristics can be included in the embodiment. 
         [0018]    Throughout this disclosure, the numerical values represent approximate measures or limits to ranges to encompass minor deviations from the given values and embodiments having about the value mentioned as well as those having exactly the value mentioned. Other than in the working examples provided at the end of the detailed description, all numerical values of parameters (e.g., of quantities or conditions) in this specification, including the appended claims, are to be understood as being modified in all instances by the term “about” whether or not “about” actually appears before the numerical value. “About” indicates that the stated numerical value allows some slight imprecision (with some approach to exactness in the value; approximately or reasonably close to the value; nearly). If the imprecision provided by “about” is not otherwise understood in the art with this ordinary meaning, then “about” as used herein indicates at least variations that may arise from ordinary methods of measuring and using such parameters. 
         [0019]    As referred to herein, ranges are, unless specified otherwise, inclusive of endpoints and include disclosure of all distinct values and further divided ranges within the entire range. Thus, for example, a range of “from A to B” or “from about A to about B” is inclusive of A and of B. Disclosure of values and ranges of values for specific parameters (such as temperatures, molecular weights, weight percentages, etc.) are not exclusive of other values and ranges of values useful herein. It is envisioned that two or more specific exemplified values for a given parameter may define endpoints for a range of values that may be claimed for the parameter. For example, if Parameter X is exemplified herein to have value A and also exemplified to have value Z, it is envisioned that Parameter X may have a range of values from about A to about Z. Similarly, it is envisioned that disclosure of two or more ranges of values for a parameter (whether such ranges are nested, overlapping or distinct) subsume all possible combination of ranges for the value that might be claimed using endpoints of the disclosed ranges. For example, if Parameter X is exemplified herein to have values in the range of 1-10, or 2-9, or 3-8, it is also envisioned that Parameter X may have other ranges of values including 1-9, 1-8, 1-3, 1-2, 2-10, 2-8, 2-3, 3-10, and 3-9. 
         [0020]    The present technology generally provides devices for anchoring a suture to a bone. The devices, for example, can be used to attach or secure soft tissue to a bone, to attach or secure bone to bone, or to attach or secure bone to structures. Non-limiting examples of soft tissue include tendons, ligaments, fascia, skin, fibrous tissues, synovial membranes, fat, muscles, nerves, and blood vessels. More particularly, the devices of the present technology include anchors that are composed of non-woven electrospun fibers. The anchors are configured such that they can be switched or transitioned from a first configuration to a second configuration when placed in a bore prepared in a bone. Additionally, the electrospun fibers mimic a physiological collagen matrix, which promotes cell growth and tissue integration, which provides mechanical stabilization to the anchor, and through the anchor, to any material attached or secured to a bone with the use of the anchor. In various embodiments, the electrospun fibers include an adjunct material, such as a modifying agent, biological agent, or antimicrobial agent that, for example, alter the anchor&#39;s response to water, enrich the fibers with cytokines or growth factors, or provide antimicrobial properties to the anchor. 
         [0021]    As used herein, the term “electrospun fibers” refers to fibers generating through electrospinning. Such electrospun fibers have diameters of from about 1 nm to about 50 μm. However, in various embodiments, the electrospun fibers have diameters of from about 0.1 μm to about 10 μm. The electrospun fibers can be generated by any process known in the art. Although many variations may exist, in general electrospun fibers are generated by creating an electric field between a sessile droplet of a polymer solution or polymer melt at the tip of a needle or pipette and a stationary collector plate or a rotating collector spool. The electric field causes a jet to issue from the sessile drop of polymer solution or melt to the collector plate or spool. By using a collector plate, collected electrospun fibers can be molded otherwise formed into a geometric shape that is solid. For example, the fibers can be molded into a porous solid structure, such as a suture anchor, with any cross-sectional geometry. As non-limiting examples, the cross sectional geometry can be a circle, oval, square, diamond, rectangle, pentagon, hexagon, heptagon, octagon, etc. Alternatively, by using a rotating collector spool, collected electrospun fibers can be slid off of the spool to generate a hollow structure, such as a suture anchor, with a cross-section geometry matching the cross-section geometry of the spool. For example, when the spool has a circular cross-sectional geometry, the hollow structure will have a circular cross-sectional geometry. Similarly, when the spool has a triangular cross-sectional geometry, the hollow structure will have a triangular cross-sectional geometry. However, hollow structures with other cross-sectional shapes can be generated by altering the shape of the rotating spool. 
         [0022]    The electrospun fibers can be generated from any polymer known in the art, such as natural degradable polymers, synthetic degradable polymers, and nondegradable polymers. Non-limiting examples of suitable natural degradable polymers include fibrin, collagen, laminin, fibronectin, elastin, chitosan, gelatin, hyaluronan, albumin, dextran, pectin, starch and combinations thereof. Non-limiting examples of suitable synthetic degradable polymers include polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL, including ε caprolactone), polydioxanone (PDO), polyhdryoxybutyrate (PHB), poly(an hydrides), poly(tri methylene carbonate) (PTC), polyphophazenes, poly amino acids, such as, for example, poly(L-lysine), epsilon poly-lysine, poly(L-ornithine) (PLO) and poly(L-glutamic acid-4-co-L-tyrosine) (PLEY), and mixtures thereof. Non-limiting examples of suitable nondegradable polymers include polyesters, polycarbonate urethanes, polypropylene (PP), nylon, polyurethane (PU), polyester urethanes, polyetherurethanes, polyvinylchloride (PVC), polyethylene (PE), poly(tetrafluroethylene (PTFE), poly(methyl acrylate) (PMA), poly(methyl methacrylate (PMMA), ethylene-co-vinylacetate (EVA), poly(dimethylsiloxane) (PDMS), poly(ethylene terephthalate) (PET), poly(sulphone) (PS), poly(ethyleneoxide) (PEO), poly(ethyleneoxide-co-prpyleneoxide) (PEO-PPO), poly(vinylalcohol) (PVA), and mixtures thereof. Whether degradable or nondegradable, in various embodiments, the polymers are polyanionic, polycationic, hydrophilic, hydrophobic, amphipathic, cross-linked, or non-cross-linked. Additionally, the electrospun fibers themselves may be hollow or solid. 
         [0023]    Various properties can be imparted into the electrospun fibers by including an adjunct material, such as a modifying agent, biological agent, antimicrobial agent, or combination thereof to the polymer during the electrospinning process. Therefore, the adjunct material can be directly incorporated into the electrospun fibers. Alternatively, the adjunct material can be indirectly incorporated into the electrospun fibers by dipping, soaking, or spraying after the electrospun fibers are generated. 
         [0024]    With reference to  FIG. 1 , the present technology provides a flexible anchor  100 . The flexible anchor  100 , for example, can be used to couple a suture to a bone. By anchoring a suture to a bone, the anchor  100  can be used to attach or secure a soft tissue to the bone. 
         [0025]    The anchor  100  comprises a tubular body  102  that extends from a first end  104  to a second end  106 . The tubular body is composed of a non-woven, non-braided material. In particular, and as shown in  FIG. 1A , the non-woven, non-braided material includes one or a plurality of fibers, such as electrospun fibers  116  generated from the polymers described above. Accordingly, the electrospun fibers  116  interact with each other to form a network of electrospun fibers  118 . In various embodiments, the anchor  100  comprises a single electrospun fiber  116  that is randomly wrapped, spun, coiled, or twisted about itself to generate the network  118 . In other embodiments, the anchor  100  comprises a plurality of electrospun fibers  116  that are randomly wrapped, spun, coiled, or twisted about each other to generate the network  118 . Accordingly, the anchor  100  comprises at least one electrospun fiber  116  that forms an electrospun fiber network  118 . In  FIG. 1 , the anchor  100  is hollow and comprises an internal passage  108  that extends through and along the tubular body  102  from the first end  104  to the second end  106 . When the anchor  100  is hollow, the tubular body  102  includes a cylindrical wall that defines the internal passage  108 . The cylindrical wall has a diameter or thickness of from about 0.1 mm to about 10 mm, or from about 0.5 mm to about 2 mm, or from about 2 mm or less. However, in other embodiments, not shown, the anchor  100  is not hollow, i.e., it is solid, and does not comprise the internal passage  108 . Examples of methods for generating hollow and solid anchors with the electrospun fibers  116  are provided above. 
         [0026]    The flexible anchor  100  can have any properties that allow the flexible anchor  100  to change shape. In this regard, the flexible anchor  100  can be, for example, compliant, flexible, foldable, squashable, squeezable, deformable, limp, flaccid, elastic, low-modulus, soft, spongy or perforated, or have any other characteristic property that allows it to change shape. In some embodiments, the flexible anchor  100  includes an adjunct material or modifying agent. 
         [0027]    The electrospun fibers  116  have a size that is much smaller than the size of filaments of typical yarns used to braid sutures. As such, the electrospun fibers  116  in the flexible anchor  100  have a diameter of from about 1 nm to about 50 μm. In some embodiments, the electrospun fibers  116  have a diameter that is near the size of mammalian tissues, such as collagen fibrils or collagen fiber bundles. Such electrospun fibers  116  have a diameter of from about 0.1 μm to about 10 μm and are mimetic of normal extracellular matrix components in terms of size and shape, which encourages cellular attachment and tissue ingrowth when positioned within a bore prepared in a bone (see  FIGS. 2 and 3 ). Over time, cellular attachment and tissue ingrowth increases the mechanical strength and stability of the anchor  100 . Additionally, the wrapping, spinning, coiling, and/or twisting of the electrospun fibers  116  defines void volumes or pores between individual electrospun fibers  116  or between folds of a single electrospun fiber  116 . Accordingly, the network of electrospun fibers  118  includes void volumes or pores. 
         [0028]    As discussed above, in various embodiments the electrospun fibers  116  in the flexible anchor  100  include an adjunct material, such as a modifying agent, biological agent, or antimicrobial agent. Modifying agents include agents that alter, change, or enhance a property of the polymer included in the fibers  116 . Such modifying agents may, for example, promote cellular attachment to the flexible anchor  100 . In particular, hydrophilic agents can be used to impart hydrophilic properties upon hydrophobic polymers, or to enhance hydrophilic properties of hydrophilic polymers. Non-limiting examples of hydrophilic modifying agents that promote cellular attachment to the anchor  100  by way of the electrospun fibers  116  include chitosan, gelatin, collagen, silk fibroin, polyethylene glycol, poly-L-lysine, epsilon poly-lysine, blood serum albumin, elastin, fibronectin, hydrophilic biocompatible proteins or combinations thereof. Additionally, modifying agents include agents that provide osteoconductive and/or osteogenic properties to the electrospun fibers  116 , such as, for example, ceramic materials selected from the group consisting of tricalcium phosphate, hydroxyapatite, bioglass, and combinations thereof. 
         [0029]    In some embodiments, the electrospun fibers  116  include a biological agent that leaches into surrounding tissues after implantation or that contacts cells or tissues that infiltrate the flexible anchor  100 . Therefore, the flexible anchor can serve as a drug delivery device. The biological agent can be a growth factor, a small molecule drug, or other molecule that stimulates cell infiltration, and/or that encourages differentiation and maturation of repair tissue, stimulates osteoblast activity, decreases osteoclast activity, and/or that decreases inflammation. Non-limiting examples of suitable biological agents include immunomodulatory host defense proteins, immunomodulatory synthetic mimics of host defense proteins, bisphosphonates, parathyroid hormone, teriparatide, recombinant parathyroid hormone derivatives, parathyroid hormone fragments, strontium ranelate, phenamil, naringin, interleukin-1 receptor antagonist (IL-1ra), soluble interleukin-1 receptor II (sIL-1RII), soluble tumor necrosis factor-receptor 1 (sTNF-RI), soluble tumor necrosis factor-receptor 2 (sTNF-RII), fibroblast growth factor (FGF), bone morphogenetic growth factors (BMPs, including BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, and BMP7), insulin-like growth factor (IGF-I), epidermal growth factor EGF), hepatocyte growth factor (HGF), platelet-derived growth factor AB (PDGF-AB), platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor-β1, (TGF-β1), and mixtures thereof. The biological agents that are proteins can be recombinant or non-recombinant, such as, for example, non-recombinant PDGF or recombinant PDGF. 
         [0030]    In some embodiments, the electrospun fibers  116  include an antimicrobial agent that leaches into surrounding tissues after implantation or that contacts unwanted microbes that come into contact with the flexible anchor  100 , such as undesired microbes incorporated during a surgical implantation of the anchor  100 . Undesired microbes include bacteria, viruses, and fungi; therefore, the antimicrobial can be an antibiotic, an antiviral agent, an antifungal agent, or a combination thereof. Antibiotics useful herein include, for example, rifamycins (such as rifampin), tetracylines, fosfomycin, fusidic acid, glycylcyclines, aminoglycosides, quinolones, glycopeptides, bismuth thiols, sulfonamides, trimethoprim, macrolides, oxazolidinones, β-lactams, lincosamides, chloramphenicol, gramicidins, polymyxins, lipodepsipeptides, bacitracins, tetracyclines (such as minocycline), penicillin, ampicillin, cefazolin, clindamycin, erythromycins, levofloxacin, vancomycin, gentamycin, and mixtures thereof. In one embodiment, the antimicrobial agent comprises a mixture of vancomycin and gentamycin. Tetracycline antibiotics refer to a number of antibiotics of either natural, or semi-synthetic origin, derived from a system of four linearly annealed six-membered rings (1,4,4a,5,5a,6,11,12a-octahydronaphthacene) with a characteristic arrangement of double bonds. The tetracycline antibiotic can include one or more tetracyclines, and/or semi-synthetic tetracyclines such as doxycycline, oxytetracycline, demeclocycline, lymecycline, chlortetracycline, tigecycline and minocycline. A preferred tetracycline is minocycline or minocycline hydrochloride. Rifamycin class of antibiotics is a subclass of antibiotics from the ansamycin family of antibiotics. The present antibiotic agent or agents can include one or more rifamycin antibiotics from the group rifamycin B, rifampin or rifampicin, rifabutin, rifapentine and rifaximin. Antiviral agents include acyclovir, adenosine, arabinoside, thiadiazoles interferon and interferon inducing agents. Antifungal agents include amphotericin B, imidazoles, triazoles, thiazoles, allylamines, echinocandins, benzoic acid, hydroxypyridones, and 5-fluorocytosine. Antimicrobial peptides useful herein include, for example, host defense proteins, synthetic mimics of host defense proteins, defensins, magainins, cathetlicidins, protegrins, lantibiotics, nisins, and epsilon poly-lysine. Antiseptics and disinfectants include, for example, chlorhexidine, polyhexanide, triclosan, and iodine-delivering formulas such as betadine or povidone-iodine. Metal ions include various formulations of silver that effectively release silver ions, including silver salts and silver nanoparticles, or copper salts and copper nanoparticles that release copper ions. Other antimicrobial agents useful herein include salicylic acid and its metabolite methyl salicylate, and sugar alcohols and polyols (such as xylitol and erythritol). Such sugar alcohols can have antimicrobial properties by preventing bacterial adhesion or bacterial biofilm formation. Polysaccharides, such as chitosan and alginate, are also useful herein. 
         [0031]    With further reference to  FIG. 1 , and as shown in  FIGS. 2 and 3 , a suture  202  can be passed through a first opening  110  in a wall of the flexible anchor  100 , guided into and along the passage  108 , and passed out of the passage  108  through a second opening  112  in a wall of the flexible anchor  100  to form a suture construct  200  having free ends  204  and  206 . The openings  110 ,  112  can be positioned intermediately between the first and second ends  104 ,  106  of the flexible anchor  100  at a distance of, for example, one-quarter length from ends  104 ,  106 . It will be appreciated that the openings  104 ,  106  can be apertures or voids in flexible anchor  100 . In embodiments where the anchor  100  is solid and does not comprise the internal passage  108 , the suture  202  can be guided through the solid tubular body  102  with a needle. For example, the suture  202  can be coupled to a needle and the needle can pierce the tubular body  102  inward at a first location to generate the first opening  110 , which may be referred to as an “in opening”. The needle then leads and guides the suture  202  through the solid tubular body  102  and pierces the tubular body outward at a second location to generate the second opening  112 , which may be referred to as an “out opening”. Again, the openings  110 ,  112  can be positioned intermediately between the first and second ends  104 ,  106  of the flexible anchor  100  at a distance of, for example, one-quarter length from ends  104 ,  106 . In any embodiment, portions of the flexible anchor  100  between the first and second ends  104 ,  106  and the corresponding first and second openings  110 ,  112 , can define anchoring leg or tail portions  114  that can provide additional resistance for securing the flexible anchor  100  relative to a bone, as will be discussed in greater detail herein. In one exemplary configuration, suture  202  can pass only through openings  110 ,  112  and a portion of the tubular body  102  extending therebetween to form a loop that does not extend through tail portions  114 . 
         [0032]    The anchor  100  is configured to be positioned in a prepared bore  300 , as shown in  FIGS. 2 and 3 . The flexible anchor  100  can include a first profile or shape  120  that allows for insertion into the prepared bore  300 . In other words, the first anchor  100  has the first profile while being carried into the bore  300 . During axial translation, the tail portions  114  can facilitate frictional engagement with sidewalls  302  of the bore  300 . Therefore, with the flexible anchor  100  fully seated in bore  300 , the free ends  204 ,  206  of suture construct  200  can be pulled in a direction that is generally coaxial with and away from bore  300  to thereby set the flexible anchor  100  in an anchoring configuration relative to a cortical bone layer  304  of a bone  306 , such as, for example, a glenoid. In one exemplary configuration, during setting of flexible anchor  100 , portions of the anchor  100 , including tail portions  114 , can bunch together, collapse, expand and/or change shape to a second shape, configuration or locking profile  130  to form an anchoring mass  140 . The anchoring mass  140  can then be set or seated against an inner face of cortical bone layer  304  surrounding bore  300 . In an exemplary configuration, second shape or profile  130  can include a width that is greater than that of first profile  120  and that of the initially formed bore  300  such that portions of flexible anchor  100  can expand into a cancellous bone layer  308  and extend transversely beyond the width or diameter of the bore  300  beneath the cortical bone  304 . For example, the anchoring mass  140  can include a width in a direction perpendicular to a longitudinal axis of the bore  300  greater than the width of first profile  120  and the width of initially formed bore  300 . In an exemplary configuration, the flexible anchor  100  can lock against a ledge  310  of the cortical bone layer  304 , as shown in  FIG. 3 . In various embodiments, the anchor  100  and suture construct  200  is inserted into the bore  300  with a device described in U.S. Pat. No. 8,562,647, issued to Kaiser et al on Oct. 22, 2013, which is incorporated herein by reference in its entirety. The free ends  204 ,  206  of the suture  202  are configured, for example, to secure a soft tissue to the bone  306  after the suture assembly  200  is switched to the second locking configuration  130 . 
         [0033]    The foregoing description of the embodiments has been provided for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosure. Individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but, where applicable, are interchangeable and can be used in a selected embodiment, even if not specifically shown or described. The same may also be varied in many ways. Such variations are not to be regarded as a departure from the disclosure, and all such modifications are intended to be included within the scope of the disclosure.