WO2009102776A2 - Tissue-fastening articles and devices, and related methods - Google Patents

Abstract

Suitable tissue-fastening articles and devices that can incorporate and/or be encapsulated by one or more potyphosphazenes are provided, including various surgical fastening devices ('SFD'), sutures, surgical staples, screws, and other equivalent tissue-fastening devices, which exhibit exceilent mechanical and physical tolerance properties, in order to improve the biocompatibiiity of such sheathed implanted devices, and to prevent or diminish various secondary injuries following a treatment or an implantation. The poiyphosphazenes coating of various tissue-fastening articles and devices imparts substantial advantages to such articles and devices, including the prevention or minimization of uncontroilεd cellular growth, and reduction in various inflammatory reactions following the implantation of a foreign material into a patient's body, and thereby, reducing the amount of antibiotics necessary to treat infections attendant with such implantation and subsequent inflammatory reactions.

Description

TISSUE-FASTENING ARTICLES AND DEVICES, AND RELATED METHODS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C §119(e) of U.S. Provisional Patent Application No. 61/027,522, filed February 1 1, 2008, incorporated herein by reference in its entirety.

TECHNICAL FIELD

[0002] This disclosure relates to various implantable articles/devices, incorporating and/or encapsulated by polymers, that can facilitate tissue enclosure and can promote tissue healing.

BACKGROUND

[0003] Various articles and devices have been developed to mediate tissue enclosure, either temporarily during surgical procedures, or intended to be permanently implanted within patients pursuant to surgery. The integrity of such tissue-enclosing articles and devices can be compromised by the application of physical stress, or by incurring significant tissue damage resulting from the activation of certain deleterious biological responses to implantation of such devices. Improved products that can be employed as tissue-fastening articles and devices exhibiting superior biocompatibility are highly desirable.

BRIEF SUMMARY

[0004] Various tissue-fastening articles and devices that can incorporate and/or be encapsulated by various phosphazenes of general formula (I) are disclosed. Suitable tissue-fastening articles and devices include surgical fastening devices ("SFD"), sutures, wires, surgical staples, brackets, pins, bolts, tacks, sσews, support meshes, and other equivalents.

DESCRIPTION OF THE DRAWINGS [0005] FIG. 1 is an exemplary σoss-sectional perspective of a single fiberoptic structural fiber, as one embodiment of the present disclosure.

[0006] FIG. 2 is a longitudinal perspective of an exemplary suture that can terminate in a fiberoptic connector, as one embodiment of the present disclosure. [0007] FIG. 3 is a longitudinal perspective of an alternate exemplary suture that may terminate in a fiberoptic connector, as another embodiment of the present disclosure.

[0008] FIG. 4A is a longitudinal perspective of an exemplary surgical screw, as one embodiment of the present disclosure. [0009] FIG. 4B is a cross-sectional perspective through the shaft of the surgical sσew at the level of A-A' of FIG. 4A, as one embodiment of the present disclosure.

[0010] FIG. 4C is a schematic showing an exemplary screwdriver bit for use with the surgical screw of FIG. 4A, as one embodiment of the present disclosure.

[0011] FIG. 5A is a schematic showing an exemplary surgical staple, as one embodiment of the present disclosure.

[0012] FIG. 5B is a schematic showing an alternate exemplary surgical staple, as one embodiment of the present disclosure. [0013] FIG. 5C is a schematic showing an exemplary surgical stapling device for use with the surgical staple of FIGS. 5A-B, as one embodiment of the present disclosure.

[0014] FIG, 6A is a schematic showing an exemplary vascular clip, as one embodiment of the present disclosure. [0015] FIG. 6B is a cross-sectional perspective of the exemplary vascular clip at the plane of line of A-A' through the jaws of FIG. 6A, as one embodiment of the present disclosure.

[0016] FIG. 6C is a schematic showing an exemplary clip applicator for use with the vascular clip of FIG. 6A-B, as one embodiment of the present disclosure.

[0017] FIG. 7A is a schematic showing an exemplary fixation plate, as one embodiment of the present disclosure.

[0018] FIG. 7B is a cross-sectional perspective of the exemplary fixation plate of at plane of line A-A' FIG. 7A, as one embodiment of the present disclosure.

DETAILED DESCRIPTION OF EMBODIMENTS

Definitions [0019] In addition to the definition of terms provided below, the terms "a" or "an" mean one or more of the referenced subject matter. [0020] The term "tissue-fastening" refers to any articles and/or devices that can be employed for stabilizing, supporting, holding, pulling, and/or buttressing injured tissues and organs. [0021] The term "encapsulation" and "coating" can be used interchangeably to refer to an enclosure of a structural element or a member or a feature or a component of an item ("substrate"), in part or in its entirety, including any surfaces thereof, by employing various polymers of general formula (I). Suitable substrates for coating include various surgical fastening devices ("SFD"), sutures, wires, surgical staples, brackets, pins, bolts, tacks, screws, support meshes, and other equivalents.

[0022] The term "incorporation" refers to the structural integration of polymers of general formula (I) into a suitable tissue-fastening articles and/or devices, such as sutures and support meshes, in which the polyphosphazene polymers can be incorporated as components of fibers that can be formed as sutures and support meshes.

[0023] The terms "bioresorbable" and "bioabsorbable" can be used interchangeably to mean capabie of degradation in vivo, by dissolution and/or assimilation, that do not require mechanical removal.

Incorporation and/or Encapsulation of Tissue-Fastening Articles and Devices by Polvphosphazenes of Formula (X)

[0024] Various embodiments are directed to various tissue-fastening articles and devices comprising polymers of general formula (I). Suitable tissue-fastening articles and devices that can incorporate and/or be encapsulated by one or more polyphosphazenes of Formula (I) include: surgical fastening devices ("SFD"), sutures, surgical staples, screws, and other equivalent tissue-fastening devices, which exhibit excellent mechanical and physical tolerance properties, in order to improve the biocompatibility of such sheathed implanted devices, and to prevent or diminish various secondary injuries following a treatment or an implantation. The coating of various tissue-fastening articles and devices with polymers of general formula (I) imparts substantial advantages to such articles and devices, including the prevention or minimization of uncontrolled cellular growth, and reduction in various inflammatory reactions following the implantation of a foreign material into a patient's body, and thereby, reducing the amount of antibiotics necessary to treat infections attendant with such implantation and subsequent inflammatory reactions.

[0025] U.S. Patent 7,021,808, incorporated in its entirety, discloses polyphosphazene polymers of formula (I) that can exhibit excellent anti- thrombogenic effect as a bulk material (cf. Tur, Untersuchungen zur Thrombenresistenz von Poly[bis(trifluoroethoxy)phosphazen] und Hollemann - Wiberg, "StickstoffVerbindungen des Phosphors", Lehrbuch der anorganischen Chemie 666-669, 91st 100th Edition, Walter de Gruyter Verlag 1985; also Tur, Vinogradova, et al., "Entwicklungstendenzen bei polymeranalogen Umsetzungen von Polyphosphazenen," Acta Polymerica 39: 424-429, (8), 1988). Patent Specification DE 196 13 048 disclosed polyphosphazenes as a suitable coating for artificial implants.

[0026] Various embodiments are directed to various tissue- enclosing/tissue-fastening articles and/or devices comprising a polymeric compound poly[bis(trifluoroethoxy) polyphosphazene] and/or derivatives thereof.

[0027] Various embodiments are directed to tissue-fastening articles and devices comprising a supportive member and at least one polymer component having the general formula (I):

in which the n value is an integer from 2 to oo; R¹ to R⁶ are independently selected from: a substituted or unsubstituted alkyl, alkoxy, aryl, aryloxy, silyl, silyloxy, alkylsulfonyl, alkyl amino, dialkyl amino, ureido, carboxylic acid ester, alkylmonoamidine, alkylbisamidine, alkoxymonoamidine, or alkoxybisamidine; or an amino; a heterocyclic alkyl group with at least one nitrogen, phosphorus, oxygen, sulfur, or selenium as a heteroatom; a heteroaryl group with at least one nitrogen, phosphorus, oxygen, sulfur, or selenium as the heteroatom; a nucleotide or a nucleotide residue; a biomacromolecule; or a pyrimidine or a purine base. C0028] Suitable sυbstituents for R¹ to R⁶ can be independently selected from: halide substituents, such as fluorine, chlorine bromine, or iodine; pseυdohalide sυbstituents, such as cyano (-CN), isocyano (-NC), thiocyano (- SCN), isothiocyano (-NCS), cyanato (-OCN), isocyanato (-NCO), azido (-N₃) groups; substituents such as nitro- (-NO2) and nitrito (-NO) groups; partially substituted afkyl groups, such as haloalkyf; heteroaryl such as imidazoyl, oxazolyl, thiazolyl, pyrazolyl derivatives; or purine and pyrimidine bases such as guanidines, amidines and other ureido derivatives of the base structure.

[0029] As used herein, alkyl (R), alkoxy (-OR), alkylsulfonyl (-SO2R), alkyl amino (-NHR), dialkyl amino (-NR2), carboxylic acid ester (-

(alkadiyl)C(O)OR or -alkadiyl)OC(O)R)), ureido (-NHC(O)NH2, -NRC(O)NH2, -

NHC(O)NHR, -NRC(O)NHR, -NHC(O)NR2, -NRC(O)NR2, and their alkadiyl- linked analogs), alkylmonoamidine (including -N=C(NR2)R, -(alkadiyl)N=C-

(NR2)R, -C(NR2)=NR, and -(alkadiyl)C(NR2)=NR), alkylbisamidine (including - N=C(NR2)2, -(alkadiyl)N=C(NR2)2, -NRC(NR2)=NR, and

(alkadiyl)NRC(NR2)=NR), alkoxymonoamidine (-O(alkadiyl)N=C(NR2)R, - 0C(NR2)=NR, and -O(alkadiyl)C(NR2)=NR)), and alkoxybisamidine (- O(alkadiyl)N=C(NR2)2, -O(alkadiyl)NRC(NR2)=NR, and

O(alkadiyl)NRC(NR2)=NR) moieties are defined by the corresponding formula shown, in which R can be selected independently from a linear, branched, and/or cyclic ("cycloalkyl") hydrocarbyl moieties, including alkyl (saturated hydrocarbons) as well as alkenyJ and alkynyl moieties, having from 1 to 20 (for example, from 1 to 12, or 1 to 6) carbon atoms.

[0030] The inclusion of alkenyl and alkynyl moieties provides, among other things, the capability to cross-link the polyphosphazene moieties to any extent desired. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, t-butyJ, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4- trimethylpentyl, nonyl, decyl, undecyl and dodecyl. Cydoalkyl moieties may be monocyclic or multScyclic, and examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl. Additional examples of alkyl moieties have linear, branched and/or cyclic portions (e.g., l-ethyl-4-methyl- cyclohexyl).

[0031] According to this definition and usage (supra), specific examples of R (alkyl) groups include unsubstituted alkyl, substituted alkyl such as halo- substituted alkyl (haloalkyl), unsubstituted alkenyl, substituted aikenyl such as halo-substituted alkenyl, and unsubstituted alkynyl, and substituted alkynyl such as halo-substituted alkynyl.

[0032] Furthermore, these examples of R (alkyl) provide that the alkoxy (OR) substituents can be unsubstituted alkoxy ("alkyloxy"), substituted alkoxy such as halo-substituted alkoxy (haloalkoxy), unsubstituted alkenyloxy, substituted alkenyloxy such as halo-substituted alkenyloxy, unsubstituted alkynyJoxy, and substituted alkynyloxy such as halo-substituted alkynyloxy. In this aspect, vinyloxy and allyloxy can be useful.

[0033] A silyl group is a -SiR3 group and a silyloxy group is an -0SiR3 group, where each R moiety is selected independently from the R groups defined supra. That is, R in each occurrence is selected independently from a linear, branched, and/or cyclic ("cycloalkyl") hydrocarbyl moieties, including alkyl (saturated hydrocarbons) as well as alkenyi and alkynyl moieties, having from 1 to 20 (for example, from 1 to 12, or 1 to 6) carbon atoms. [0034] Unless otherwise specified, any R group can be unsubstituted or substituted independently with at least one substituent selected from a halogen (fluorine, chlorine, bromine, or iodine), an alkyl, an alkylsulfonyl, an amino, an alkylamino, a dialkylamino, an amidino (-N=C(NH2)2), an alkoxide, or an aryloxide, any of which can have up to 6 carbon atoms, if applicable. Thus, the term substituted "alkyl" and moieties which encompass substituted alkyl, such as "alkoxy", include haloalkyl and haloalkoxy, respectively, including any fluorine-, chlorine-, bromine-, and iodine-substituted alkyl and aikoxy. Thus, terms haloalkyl and haloalkoxy refers to alkyl and alkoxy groups substituted with one or more halogen atoms, namely fluorine, chlorine, bromine, or iodine, including any combination thereof. [0035] Unless otherwise indicated, the term "aryl" means an aromatic ring or an aromatic or partially aromatic ring system composed of carbon and hydrogen atoms, which may be a single ring moiety, or may contain multiple rings bound or fused together. Examples of aryl moieties include, but are not limited to, phenyl, anthracenyl, azulenyl, biphenyl, fluorenyl, indan, indenyl, naphthyl, phenanthrenyl, 1,2,3,4-tetrahydro-naphthalene, toiyl, and the like, any of which having up to 20 carbon atoms. An aryloxy group refers to an -O(aryl) moiety.

[0036] The terms haloaryl and haloaryloxy refer to aryl and aryloxy groups, respectively, substituted with one or more halogen atoms, namely fluorine, chlorine, bromine, or iodine, including any combination thereof.

[0037] A heterocyclic alky! group with at least one nitrogen as a heteroatom refers to a non-aromatic heterocycle and includes a cycloalkyl or a cydoalkenyl moiety in which one or more of the atoms in the ring structure is nitrogen rather than carbon, and which may be monocyclic or multicyclic, and may include exo-carbonyl moieties and the like. Examples of heterocyclic alky! group with nitrogen as a heteroatom include, but are not limited to, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydropyrimidinyl, morpholinyl, aziridinyl, imidazolidinyi, 1-pyrroline, 2-pyrroline, or 3-pyrroline, pyrrolidinonyl, piperazinonyl, hydantoinyl, piperidin-2-one, pyrrolidin-2-one, azetidin-2-one, and the like. Thus, these groups include heterocyclic exocyclic ketones as well.

[0038] A heteroaryl group with at least one nitrogen as the heteroatom refers to an aryl moiety in which one or more of the atoms in the ring structure is nitrogen rather than carbon, and which may be monocyclic or multicyclic. Examples of heterocyclic alkyl group with nitrogen as a heteroatom include, but are not limited to, acridinyl, benzimidazolyl, quinazolinyl, benzoquinazolinyl, imidazolyl, indolyl, isothiazolyl, isoxazolyl, oxazolyl or oxadiazolyl, phthalazinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolinyl, tetrazolyl, thiazolyl, triazinyl, and the like. In this aspect, this disclosure includes or encompasses chemical moieties found as sυbuntts in a wide range of pharmaceutical agents, natural moieties, natural biomolecules, and biomacromolecules. For example, this disclosure encompasses a number of pharmaceutical agents available with the tetrazole group (for example, losartan, candesartan, irbesartan, and other Angiotensin receptor antagonists); the triazole group (for example, fluconazole, isavuconazote, itraconazole, voriconazole, pramiconazole, posaconazole, and other antifungal agents); diazoles (for example, fungicides such as Miconazole,, Ketoconazole, Clotrimazole , Econazole, Bifonazote, Butoconazole, Fenticonazole, Isoconazole, Oxiconazole, Sertaconazole, Sulconazole, Tioconazole, and the like); and imidazoles (histidine, histamine, and the like). Thus in one aspect, some of the Rl to R6 moieties in the formula I can encompass chemical moieties found as subunits in a wide range of pharmaceutical agents, natural moieties, natural biomolecules, and biomacromolecules. [0039] A heterocyclic alky! group with at least one phosphorus, oxygen, sulfur, or selenium as a heteroatom refers to a non-aromatic heterocycle and includes a cycloalkyl or a cycloalkenyl moiety in which one or more of the atoms in the ring structure is phosphorus, oxygen, sulfur, or selenium rather than carbon, and which may be monocyclic or multicyclic, and may include exo-carbonyl moieties and the like. Similarly, a heteroaryl group with at least one phosphorus, oxygen, sulfur, or selenium as the heteroatom refers to an aryJ moiety in which one or more of the atoms in the ring structure is phosphorus, oxygen, sulfur, or selenium rather than carbon, and which may be monocyclic or multicyclic. Examples of heterocyclic alkyl groups or heteroaryls with phosphorus, oxygen, sulfur, or selenium as a heteroatom include, but are not limited to, substituted or unsubstituted ethylene oxide (epoxides, oxiranes), oxirene, oxetane, tetrahydrofuran (oxolane), dihydrofuran, furan, pyran, tetrahydropyran, dioxane, dioxin, thiirane (episulfides), thietane, tetrahydrothiophene (thiolane) dihydrothiophene, thiophene, thiane, thiine (thiapyrane), oxazine, thiazine, dithiane, dithietane, and the like. Thus, these groups include all isomers, including regioisomers of the recited compounds. For example, these groups include 1,2- and 1,3- oxazoles, thiazoles, selenazoles, phosphazoles, and the like, which include different heteroatoms from the group 15 or group 16 elements.

[0040] As used herein, a nucleotide refers to an organic compound containing a nitrogenous base, a sugar moiety, and one or more phosphate groups. The most common nucleotides contain either a purine or pyrimidine nitrogenous base (for example, guanine, adenine, thymine, cytosine and uracil), typically bonded to a pentose (5-carbon) sugar such as a ribose or a deoxyribose sugar, which itself is bonded to one or more phosphate groups. The term nucleotide is also used to include those materials commonly known for use as monomers for nucleic acids (such as RNA and DNA) as well as cofactors, moieties, derivatives, and portions thereof, including, for example Coenzyme A (CoA), FAD (flavin adenine dinucleotide), NAD (nicotinamide adenine dinudeotide), NADP (nicotinamide adenine dinucleotide phosphate), other dinucleotides, and the like. Similarly, as used herein, a nucleotide residue includes nucleosides, deoxynucleosides, and similar materials, examples of which include but are not limited to, adenosine, guanosine, 5- methyluridine, uridine, cytidine, deoxyadenosine, deoxyguanosine, deoxythymidine, deoxyuridine, and deoxycytidine, and the like.

[0041] As used herein, the term biomacromolecule is used in its usual manner to describe a naturally-occurring substance of large molecular weight

By way of example, biomaσomolecules include, but are not limited to, substances such as proteins, peptides, polypeptides, sugars, aminoglycans, hormones, peptides and proteins of biological or synthetic origin embedded into or attached to or diffused into the surface of the matrix material, for example, cell signaling factors, growth factors, hormones, RDG ceil signaling peptide sequences, such as integrin or disintegrin complexes, cell differentiation agents, cell apoptosis signaling factors, ceil proliferation signaling factors, extracellular and intracellular matrix proteins, nucleotide sequences, such as mRNA, μRNA, SIRNA, RNA, DNA, and the like. Integrins can be particularly useful as they can aid with integration and vessel wall healing when used in conjunction with this disclosure. [0042] As used herein, a purine base is a class of heterocyclic aromatic compounds containing a pyridimine ring fused to an imidazole ring, and including substituted purines and their taυtomers. Examples of purines include, but are not limited to, purine, adenine, guanine, hypoxanthine, xanthine, theobromine, caffeine, uric acid, isoguanine, and the like. Examples of a pyrimidine base include, but are not limited to, pyrimidine, uracil, thymine, and cytosine.

[0043] In various embodiments directed to the polyphosphazenes of formula (I), Rl to R6 are all trifluoroethoxy (OCH2CF3) groups, and whereinthe n value may vary from at least about 40 to about 100,000 Daltons. Alternatively, one may use derivatives of polymer of formula (I). The term "derivative" or "derivatives" is meant to refer to polymers made up of monomers having the structure of formula (I), wherein one or more of the Rl to R6 functional group(s) is replaced by a different functional group(s), such as an unsubstituted alkoxide, a halogenated alkoxide, a fluorinated alkoxide, or any combination thereof, or where one or more of the Rl to R6 is replaced by any of the other functional group(s) disclosed herein, but where the biological inertness of the polymer is not substantially altered.

[0044] In various embodiments directed to the polyphosphazenes of formula (I), for example, at least one of the substituents R¹ to R⁶ can be an unsubstituted alkoxy substituent, such as methoxy (OCH₃), ethoxy

(OCH₂CH₃) or n-propoxy (OCH₂CH₂CH₃)- In another aspect, for example, at least one of the substituents R¹ to R⁶ is an alkoxy group substituted with at least one fluorine atom. Examples of useful fluorine-substituted alkoxy groups R¹ to R⁶ include, but are not limited to OCF₃, OCH₂CF₃,

OCH₂CH₂CF₃, OCH₂CF₂CF₃, OCH(CF₃)₂, OCCH₃(CF₃)₂, OCH₂CF₂CF₂CF₃,

OCH₂(CF₂)_SCF₃, OCH₂(CF₂)₄CF₃, OCH₂(CF₂)_SCF₃, OCH₂(CF₂)₆CF₃,

OCH₂(CFz)₇CF₃, OCH₂CF₂CHF₂, OCH₂CF₂CF₂CHF₂, OCH₂(CF₂)₃CHF₂,

OCH₂(CF₂)₄CHF₂, OCH₂(CF₂)sCHF₂, OCH₂(CF₂)₆CHF₂, OCH₂(CF₂)₇CHF₂, and the like. Thus, while trifluoroethoxy (OCH₂CF₃) groups are preferred, these further exemplary functional groups also may be used alone, in combination with trifluoroethoxy, or in combination with each other. In one aspect, examples of especially useful fluorinated alkoxide functional groups that may be used include, but are not limited to, 2,2,3,3,3- pentafluoropropyloxy (OCH₂CF₂CF₃), 2,2,2,2',2',2'-hexarluorøisopropyloxy (OCH(CFs)₂), 2,2,3,3,4,4,4-heptafluorobutyloxy (OCH₂CF₂CF₂CF₃), 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctylOxy (OCH₂(CF₂)TCF₃), 2,2,3,3,- tetrafluoropropyloxy (OCH₂CF₂CHF₂), 2,2,3,3,4,4-hexafluorobutyloxy (OCH₂CF₂CF₂CHF₂), 3,3,4,4,5,5,6,6,7,7,8,8-dodecafluorooctyloxy

(OCH₂(CF₂)7CHF₂), and the like, including combinations thereof.

[0045] Furthermore, in alternative embodiments, 1% or less of the R¹ to R⁶ groups may be alkenoxy groups, a feature that can promote crosslinking to produce a phosphazene polymer exhibiting more elastomeric properties. In this aspect, alkenoxy groups include, but are not limited to, OCH₂CH=CH₂, OCH₂CH₂CH=CH₂, allylphenoxy groups, and the like, including combinations thereof. Also in formula (I), the residues R¹ to R^δ are each independently variable, and therefore can be the same or different

[0046] By indicating that the n value can be as large as 00 in formula (I), wherein Rl through R6 are all trifluoroethoxy (OCH₂CF₃) groups, the polymers of formula (I) include polyphosphazene polymers that can have an average molecular weight of up to about 75 million Daltons.

[0047] In various embodiments, consistent with n values, the polymers of formula (I) include polyphosphazene polymers having an average molecular weight ranging from about 40 to about 100,000 Daltons. In another embodiment, the polymers of formula (I) include polyphosphazene polymers having an average molecular weight ranging from about 1,000 to about 70,000 Daltons; from about 4,000 to about 50,000 Daltons; from about 7,000 to about 40,000 Daltons; or from about 13,000 to about 30,000 Daltons, In various embodiments, the degree of polymerization (n) of the biocompatible polymer according to Formula (I) is typically in a range from about 20 to about 200,000 Daftons, and generally from about 40 to about 100,000 Daltons. The terms "about" and "approximately" have the same meaning in this disclosure, and can be used interchangeably. [0048] In various embodiments, the polyphosphazene used to prepare the disclosed particles can have a molecular weight based on the above formula, which can be a molecular weight of at least about 70,000 g/mol, a molecular weight of at least about 1,000,000 g/mol, or a molecular weight from at least about 3xlO⁶ g/mol to about 2OxIO⁶ g/mol. In another embodiment, the polyphosphazenes have a molecular weight of at least about 10,000,000 g/mol. In each of these examples in which a typical lower limit of molecular weight is disclosed, the typical molecular weights can range up to about 25,000,000 g/mol, up to about 20,000,000 g/mol, or up to about 15,000,000 g/mol.

[0049] Furthermore, the polymers described by the general formula (I), useful for incorporation and/or encapsulation of a structural element for producing various tissue-fastening articles and/or devices, have at least the following requirements:

[0050] At least one of the groups R¹ to R⁶ in the polymer is preferably an alkoxy group substituted with at least one fluorine atom.

[0051] The alkyl group in the alkoxy, alkylsulfonyl and dialkyl amino groups include straight or branched chain alkyl groups with 1 to 20 carbon atoms, wherein the alkyl groups may be substituted with at least one halogen atom, such as a fluorine atom. [0052] Examples of alkoxy groups include methoxy, ethoxy, propoxy and butoxy groups, which preferably can be substituted with at least one fluorine atom. Particularly preferred is the 2,2,2-triftuoroethoxy group. Examples of alkylsulfonyl groups are methyl, ethyl, propyl and butylsulfonyl groups. Examples of dialkyl amino groups are the dimethyl, diethyl, dipropyl, and dibutylamino groups. [0053] The aryl group in the aryloxy group is, for example, a compound with one or more aromatic ring systems, wherein the aryl group can be substituted with at least one of the previously defined alkyl groups, for example. Examples of aryloxy groups are phenoxy and naphthoxy groups and derivatives thereof.

[0054] The heterocyclic alkyl group is for example a 3 or 7 membered ring system wherein at least one ring atom is a nitrogen atom. The heterocyclic alkyl group can, for example, be substituted by at least one of the previously defined alkyl groups. Examples of heterocyclic alkyl groups include piperidinyl, piperazϊnyl, pyrrolidinyl and morpholinyl groups and derivatives thereof. The heteroaryl group can be a compound with one or more aromatic ring systems, wherein at least one ring atom is a nitrogen atom. The heteroaryl group can be substituted with at least one of the previously defined alkyl groups, for example. Examples of heteroaryl groups include pyrrolyj, pyridinyJ, pyridinoyl, isoqulnoJinyl, and quinolinyl groups and derivatives thereof.

[0055] In various embodiments, the specific polyphophazene polymers having the general formula (I) can be employed for encapsulating a structural element as a coating layer, and/or for incorporating into a tissue-fastening article or device as a structural element or a component to provide mechanical support and/or tissue approximation that can promote healing and can minimize cell proliferation. Examples of tissue-fastening articles and devices include various surgical fastener devices ("SFD") known to persons skilled in the art, and refers to any mechanical tissue-fastening devices such as, but not limited to, sutures, surgical staples, suture needles, surgical wires, surgical screws, surgical pins, surgical plates, or other surgical fastening or closure devices.

[0056] In various embodiments, such surgical fastener devices can be provided as a structural element or a substrate material, suitable for encapsulation by polymers of general formula (I), in part or in whole, to confer a biocompatible coating to the surgical fastener devices. Examples of structural element or substrate material suitable for encapsulation by polymers of general formula (I), in part or in whole, include any conventional sutures and surgical fastener articles and devices known to persons skilled in the art, including but not limited to, silk, Nylon, gut, chromic gut, polyglycolic acid (Dexon®), polyglyconates (Maxon®), polydioxanes (glycoles or lactides), polyesthers (Vycril®), polycaprolactones, polyhydroxybutyrates, poly(amino acids), glycomer 631 (Biosyn®), coated braided lactomer, other polymeric materials, stainless steel, other metals and metal alloys, ceramics, and combinations thereof. [0057] In various embodiments, the thickness of a biocompatible coating layer comprising polymers of formula (I) for encapsulating exemplary surgical fastener devices ranges from about i μm to about 100 urn, from about i um to about 50 um, and from about i um to about 10 um.

[0058] In various embodiments, a surgical fastener device comprises a layer containing a sealant agent provided between the surface of a substrate and a biocompatible coating comprising polyphosphazene derivatives of formula (I). In various embodiments, a surgical fastener device comprises a structural member containing a sealant agent provided within the structure of the SFD in the form of a fiber, a film, a column, or other form suitable to provide such sealant agent in the desired proximity to the SFD and tissues at such time as the sealant action is desired.

[0059] In various embodiments, exemplary surgical fastener devices, films, and/or substrates can be encapsulated with a biocompatible coating layer comprising polymers of formula (I) by any suitable coating process known to persons skilled in the art, including various solvent ffuidized bed techniques and/or various spraying techniques. However, preferred results may be achieved by utilizing fluidized bed techniques in which the surface of interest can be passed through an air stream and can be coated by spraying during spinning within an air stream. The poly[bis(trifluorøethoxy)phosphazene or derivative polymers can be provided as a diluted solution suitable for spraying. [0060] In various embodiments, exemplary fibers or solid structural elements can be encapsulated with a biocompatible coating layer comprising polymers of formula (I) by various methods known to persons skilled in the art, including electrospinning, spinning, drawing, extrusion, or any other form of fiber production. In various embodiments, exemplary fibers polymers of formula (I) may be spun or braided with other structural fibers, including but not limited to, silk, Nylon, gut, chromic gut, polyglycolic acid (Dexon®), polyglyconates (Maxon®), polydioxanes (glycoles or lactides), polyesthers (Vycril®), polycaprolactones, polyhydroxybutyrates, poly(amino acids), glycomer 631 (Biosyn®), coated braided lactomer, other polymeric materials, stainless steel, other metals and metal alloys, ceramics, and combinations thereof.

[0061] In various embodiments, exemplary sealant agent layer or member preferably comprises a polar end-group. Examples include hydroxy, carboxy, carboxyl, amino, or nitro groups. However, type O-ED end groups can be employed, wherein O-ED stands for an alkoxy, alkylsulfonyl, dialkyl amino, or aryloxy group, or a heterocycloalkyl or heteroaryl group with nitrogen as the heteroatom, and can be varyingly substituted, e.g., by halogen atoms, especially fluorine. [0062] In various embodiments, exemplary sealant agent layer or member may include an adhesion promoter such as an organosilicon compound, preferably an amino-terminated silane, or based on aminosilane, amino-terminated alkenes, nitro-terminated alkenes, and silanes, or an alkylphosphonic acid. Aminopropyl trimethoxy silane is an exemplary preferred adhesion promoter in SFDs as described here.

[0063] In various embodiments, exemplary adhesion promoter improves adhesion of the SFD polymeric coating to the surface of the SFD material by coupling the adhesion promoter to the surface of the implant material, e.g., via ionic and/or covalent bonds, and by further coupling the adhesion promoter to reactive components, especially to polymers of general formula (I), for example via ionic and/or covalent bonds. [0064] In various embodiments, exemplary substrates of SFD can be coated by any coating method known to persons skilled in the art. Such coatings may be achieved by spin coating, spray coating, meniscus coating, roller curtain and extrusion coating techniques, in addition to plasma deposition and electrophoretic photoresistance methods.

[0065] Coatings may also be applied as a film. In general, a polyphosphazene polymeric film according to this disclosure and the wrapping are manufactured as follows:

[0066] A solution containing at least one compound of general formula (I) in a concentration of 0.1% to 99%, in a solvent, wherein this solvent is organic and polar. For example, ethyl acetate, acetone, THF, toluene, or xylenes can be used here. Mixtures of these solvents can also be used, or supplemented with other solvents. This solution is applied to a substrate that exhibits little or no adhesion to the polymer, e.g., glass, silicon, various ceramics or other appropriate materials, like polymers (PDMS, Teflon, PMMA, polycarbonate or silicones). The surfaces of the specified substrates surfaces can also be chemically modified, e.g., by introducing specific functional groups (--NH₂, -OH, -COOH, -COH, -COOMe, -CF₃, etc.).

[0067] Although the solvent can be evaporated without any additional measures, the solvent vapor concentration over the substrate is optimally set in a controlled manner, as is also the pressure and the temperature. At the start of the initial drying phase, the atmosphere over the coated substrate is to be saturated with solvent vapor, and the solvent vapor concentration is then slowly reduced over a period of several hours. The temperature can vary from -30° C. up to +90° C. The pressure during the initial drying phase can range from normal pressure to water jet pressure (20 Torr). After the initial drying phase, the coated substrate is dried further for a fixed time in an oil- pump vacuum (0.1 Torr),

[0068] The polymer of formula (I) dried on the substrate can then be peeled off the substrate as a film. Depending on the concentration of the polymer solution of formula (I) and the particular conditions during me first drying phase, this yields films of varying layer thickness ranging from 0.1 μm to 300 μm or more, preferably ranging from 0.5 μm to 30 μm, and especially preferred measuring around 5 μm,

[0069] In various embodiments, exemplary films or wrapping can also be microstructured on the surface prior to encapsulation. The structure of the substrate is carried over 1:1 to the structure of the film of the used polymer. One is not limited by the structural size of the substrate. Therefore, structures on the order of nanometers, microns or even larger or smaller can be manufactured. In addition, the embodiment used in structuring is subject to no limitation. This makes it possible to manufacture and use all structures that can be generated via photolithography, electron beams or ion beams, or lasers or other techniques. In particular, structures having an especially favorable flow profile can be generated. These include lotus structures or structures resembling the "shark skin" known from aircraft construction. The special advantage to these structures and their use in manufacturing films and wrappings lies in the reduction of so-called contact activation of the coagulation system. Polymers of formula (I) dried on the substrate can then be peeled off the substrate as a structured film and further processed. Depending on the concentration of the polymer solution of formula (I) and the discussed conditions during the first drying phase, this yields films of varying layer thickness ranging from 0.1 μm to 300 μm or more, preferably ranging from 0.5 μm to 30 μm, and especially preferred measuring around 5 μm. The film microstructure can also be obtained by directly "writing" on the already present film itself by means of laser, electron, or X-rays, or through "melt structuring", wherein a thin wire is brought to the melting point of the polymer, and then melts the desired structure into the film via direct contact.

[0070] In various embodiments, exemplary SFDs coated by polymers of formula (I) can retain excellent mechanical properties of the surgical fastener device's base material. This not only improves the biocompatibility of such SFDs as artificial implants, but also reduces uncontrolled cell growth, which, for example, may lead to excessive scarring. Moreover, using a microstructured film according to this disclosure makes it possible to virtually forestall the contact activation of the coagulation system. Suitable anti- scarring agents include: Dipyridamole, Amoxapine, Paroxetine, Prednisolone, Dipyridamole, Dexamethasone, Econazole, Diflorasone, Alprostadil, Amoxapine, Ibudilast, Nortriptyline, Loratadine, Albendazole, Pentamidine, Itraconazole, tovastatin, Terbinafine, manganese sulfate, a tricyclic compound, and other steroids known to persons skilled in the art.

[0071] in various embodiments, it may be desirable to amalgamate or otherwise fix the polymeric coated or other members of SFDs as described here once they have been delivered in satisfactory quantity and configuration to the desired targeted tissue. This is particularly desirable in cosmetic applications, where post-implantation structural failure or dislocation of SFD members might distort or compromise the initial result of tissue augmentation. In such settings, tissue adhesives or sealants such as fibrin, cyanoacrylate tissue adhesives, fibrinogen sealants, or other tissue adhesives including any tissue-compatible matrix within which the active component is retained, suitable for topical or other application to the locus of treatment It may therefore be a gel-like substance comprising pores within which the agent is held. It may be proteinaceous, and it may be biodegradable. Tissue adhesives or sealants as described here may also be provided in a film or coating, or may be provided in a fibrous form that may be integrated into the structure of SFDs as described here as disclosed herein. [0072] In various embodiments, exemplary tissue adhesives or sealants include crosslinkable macromolecular compounds of natural or synthetic origin such as such as oxidized starch or a polyaldehyde. An albumin- giutaraidehyde tissue adhesive can be employed. Suitable tissue adhesives or sealants include use of biocompatible compounds or compositions as an adhesive to affix the specific polyphosphazene polymeric coatings of SFDs. Suitable compounds or compositions that can achieve such tissue:tissue and t«ssue:polymer adhesion/interaction include compounds that can promote physical, chemical or ionic crosslinking of the polyphosphazene polymer's hydrogel core or a layered material, such as all polymeric compounds of synthetic or natural origin exhibiting a positive net charge such as polyethyleneimines, polyallylamines, DADMAC, PCPP, PVP, and other suitable compounds which may be co-injected during / or after SFD placement in this disclosure. Such crosslinking compounds or compositions can be provided in a gel type form in some embodiments as described here, interacting via net charge by means of electrostatic interaction/affinity towards the negatively charged hydrogel component of the SFDs' specific polyphosphazene polymer. [0073] In various embodiments, suitable tissue adhesives or sealants include of calcium alginates, chitosanes, hyalυronates, or any other ionically crosslinkable gels, which can transfer some of their multivalent ion content onto their surrounding environment, including the hydrogel component of the SFDs' specific polyphosphazene polymer, which can be crosslinked via the multivalent cation's presence, and thereby attached to the injected gel in-sitυ. Such compounds and compositions may be injected in a liquid form and then crosslinked (gelled) post-injection through addition of multivalent ions such as calcium.

[0074] In various embodiments, exemplary methods to create cross- linking of polymeric SFD members after their delivery to a target tissue include incorporating a photoinitiator agent in the structure of the SFDs, and photoactivating the photoinitiator agent with electromagnetic radiation after the SFDs have been suitable placed in the desired site and configuration, As used herein, photoactivation is the process by which energy in the form of electromagnetic radiation (e.g., light) is absorbed by a compound, e.g., a photoinitiator, thus "exciting" the compound, converting the energy to another form of energy, preferably chemical energy. As used herein, a "photoinitiator" is a chemical compound that produces a biological effect upon photoactivation or a biological precursor of a compound that produces a biological effect upon photoactivation. Without being bound by theory, the chemical energy, e.g., a reactive oxygen species, produced by photoactivation of the photoinitiator agent in contact with adjacent SFD members can bind and cause structural changes in the amino acids of the proteins of tissues, resulting in the formation of covalent bonds, polymerization, or cross-links between amino acids of the tissue, thus creating a proteinaceous framework that can serve to amalgamate or interconnect the plurality of SFD members delivered to the targeted tissue site. The photoinitiator agent, e.g., RB, R-5-P, MB, or N-HTP, can be dissolved in a biocompatible buffer or solution, eg., saline solution, and used at a concentration of from about 0.1 mM to 10 mM, preferably from about 0.5 mM to 5 mM, more preferably from about 1 mM to 3 mM.

[0075] As described above, the photoinitiator may be incorporated into the surface coating or shell of the SFD members prior to their delivery to the targeted tissue site. Alternately, the photoinitiator agent may be administered to the targeted tissue site after SFD delivery, e.g., by post- implantation injection into the site. An amount of photoinitiator sufficient to stain, e.g., to cover the surfaces of the SFDs implanted, may be applied. For example, at least 10 μl of photoinitiator solution, preferably 50 μi, 100 μi, 250 μi, 500 μl, or 1 ml, or more, of photoinitiator solution may be applied to the accumulated SFD members.

[0076] The electromagnetic radiation, e.g., light, is applied to the tissue at an appropriate wavelength, energy, and duration, to cause the photoinitiator to undergo a reaction to affect the structure of the polymeric shell of the SFD members to cause cross-linking and thereby cause amalgamation of the accumulated SFDs. The wavelength of light may be chosen so that it corresponds to or encompasses the absorption of the photoinitiator, and reaches the area of the tissue that has been contacted with the photoinitiator, e.g., penetrates into the region where the photoinitiator is injected. The electromagnetic radiation, e.g., light, used to achieve photoactivation of the photoinitiator agent can have a wavelength from about 350 nm to about 800 nm, preferably from about 400 to 700 nm and can be within the visible, infra red or near ultra violet spectra. The energy can be delivered at an irradiance of about between 0.5 and 5 W/cm², preferably between about 1 and 3 W/ cm². The duration of irradiation may be sufficient to allow cross linking of the polymeric shells of one or more microspheres. For example, in an exemplary embodiment, the duration of irradiation can be from about 30 seconds to 30 minutes, preferably from about 1 to 5 minutes. The duration of irradiation can be substantially longer in a tissue where the light has to penetrate a scattering layer to reach the wound, e.g., skin. For example, the duration of irradiation to deliver the required dose to a subcutaneous or intradermal site through the skin can be at least between one minute and two hours, preferably between 30 minutes to one hour.

[0077] All publications and patents mentioned in this disclosure are incorporated herein by reference in their entireties, for the purpose of describing and disclosing, for example, the constructs and methodologies that are described in the publications, which might be used in connection with the presently described methods, compositions, articles, and processes. The publications discussed throughout the text are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention. Should the usage or terminology used in any reference that is incorporated by reference conflict with the usage or terminology used in this disclosure, the usage and terminology of this disclosure controls. The Abstract of the disclosure is provided to satisfy the requirements of 37 C.F.R. § 1.72 and the purpose stated in 37 CF.R. § 1.72(b) "to enable the United States Patent and Trademark Office and the public generally to determine quickly from a cursory inspection the nature and gist of the technical disclosure." The Abstract is not intended to be used to construe the scope of the appended claims or to limit the scope of the subject matter disclosed herein. Moreover, any headings are not intended to be used to construe the scope of tie appended claims or to limit the scope of the subject matter disclosed herein. Any use of the past tense to describe an example otherwise indicated as constructive or prophetic is not intended to reflect that the constructive or prophetic example has actually been carried out. [0078] Also unless indicated otherwise, when a range of any type is disclosed or claimed, for example a range of molecular weights, layer thicknesses, concentrations, temperatures, and the like, it is intended to disclose or claim individually each possible number that such a range could reasonably encompass, including any sub-ranges encompassed therein. For example, when the Applicants disclose or claim a chemical moiety having a certain number of atoms, for example carbon atoms, Applicants' intent is to disclose or claim individually every possible number that such a range could encompass, consistent with the disclosure herein. Thus, by the disclosure that an alkyl substituent or group can have from i to 20 carbon atoms, Applicants intent is to recite that the alkyl group have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, including any range or sub-range encompassed therein. Accordingly, Applicants reserve the right to proviso out or exclude any individual members of such a group, including any sub-ranges or combinations of sub-ranges within the group, that can be claimed according to a range or in any similar manner, if for any reason Applicants choose to claim less than the full measure of the disclosure, for example, to account for a reference that Applicants are unaware of at the time of the filing of the application, EXAMPLES

EXAMPLE 1

[0079] FIG. 1 is an exemplary cross-sectional perspective of a single fiberoptic structural fiber, as one embodiment of the present disclosure. In FIG. 1, an exemplary single fiberoptic structural fiber or fiber bundle forms the core 3 of a suture 1 with an intermediate sealant agent layer 4, and an outer polymeric coating 5. The outer polymeric coating 5, may be in either permanent or bioresorbable form. Once the fiberoptic structural fiber suture 1 has been placed in tissue in the usual manner, an electromagnetic radiation source can be located in continuity witii the fiberoptic structural fiber or fiber bundle 3. This radiation exposure initiates the release and activation of the sealant agent in the intermediate sealant agent layer 4, which reacts and bonds with the suture 1 and adjacent tissues.

EXAMPLE 2

[0080] FIG. 2 is a longitudinal perspective of an exemplary suture that can terminate in a fiberoptic connector, as one embodiment of the present disclosure. In FIG. 2, a suture 10 comprises one or more fiberoptic structural fibers 14 braided with one or more sealant agent containing fibers 12. The sealant agent containing fibers 12 have an outer polymeric coating 4. The outer polymeric coating 4, for both the fiberoptic structural fibers and the sealant agent, 14 and 12, can be either permanent or bioresorbable. The suture 10 can terminate in a fiberoptic connector 6, connecting one or more fiberoptic structural fibers 14 to an electromagnetic radiation source [not shown in FIG. 2] capable of transmitting light or other electromagnetic radiation through the fiberoptic fibers. This radiation exposure initiates the release and activation of the sealant agent in the at least one sealant agent containing fiber 12, which reacts and bonds with the suture 10 and adjacent tissues. The suture 10 can terminate in at least one fiberopric connector 6 located the proximal and/or distal end of the suture.

EXAMPLE 3 [0081] FIG. 3 is a longitudinal perspective of an exemplary suture that may terminate in a fiberoptic connector, as another embodiment of the present disclosure. In FIG. 3, the suture is 10 composed of one or more fiberoptic fibers 14 braided with one or more sealant agent containing fibers 12, and at least one nonoptical structural fiber 8, all fibers are composed of either a permanent or bioresorbable polymeric coating 4. The fiberoptic structural fibers 14 can terminate at the proximal and/or distal end of the suture to a fiberoptic connector 6. The fiberoptic connector is able to connect the fiberoptic structural fibers 14 to an electromagnetic radiation source [not shown in Fig. 3] capable of transmitting light or other electromagnetic radiation through the fiberoptic fibers. This radiation exposure initiates the release and activation of the sealant agent in the at least one sealant agent containing fiber 12, which reacts and bonds with the suture 10 and adjacent tissues.

EXAMPLE 4

[0082] FIG. 4A is a longitudinal perspective of an exemplary surgical screw, as one embodiment of the present disclosure. In FIG, 4A, a surgical screw 20 has a shaft 24 with a helical thread 23 extending from a head 25 and a distal tip 22. The head of the surgical screw 20 has a driver engagement site 26 for the purpose of engaging a screwdriver bit [not shown in FIG. 4A]. [0083] FIG. 4B is a cross-sectional perspective through the shaft of the surgical screw at the level of A-A' of FIG. 4A, as one embodiment of the present disclosure. In FIG. 4B, at least one fiberoptic fiber 14 and at least one sealant agent containing fiber 12 are provided in at least one groove 18 surrounding the core 16, within the shaft 24 of the screw. The screw 20 has with an overall outer polymeric coating 4 as described here. Although, the fiberoptic fiber and sealant agent containing fiber, 14 and 12, are show in a linear arrangement, the fibers can be arranged in a non-linear, convoluted pattern, if desired.

[0084] FIG. 4C is a schematic showing an exemplary screwdriver bit for use with the surgical screw of FIG. 4A, as one embodiment of the present disclosure, In FIG. 4C, the screwdriver bit 40 comprises a shaft 42 extending from a screw engager 44 at a distal end of shaft to a proximal end that may engage a handle or power screwdriver mechanism [not shown in Fig 4C]. The screw engager 44 may be of any shape on cross-section, provided such shape is capable of securely engaging a driver engagement site 46 of the surgical screw of FIG. 4A. At least one fiberoptic fiber 45 extends the length of the shaft 42 from the distal tip of the screw engager 44 to a connection with an electromagnetic radiation source [not shown in FIG. 4A-C] capable of transmitting light or other electromagnetic radiation through the fiberoptic fiber, allowing irradiation of an implanted screw at the time of tightening.

This radiation exposure initiates the release and activation of the sealant agent in the sealant agent containing fiber 48, which reacts and bonds with the surgical screw of FIG. 4A and adjacent tissues.

EXAMPLE 5

[0085] FIG. 5A is a schematic showing an exemplary surgical staple, as one embodiment of the present disclosure. In FIG. SA, the surgical staple 500 is shown, in which at least one fiberoptic fiber 525 is provided in a groove 515 within the body 505 and legs 510 of the staple 500. A port 520, located on the face 535 of the body of the staple allows for exposure of at least one fiberoptic fiber 525 to an externally applied electromagnetic radiation source [not shown in FIG. 5A], capable of illuminating the fiberoptic fiber(s) 525. The surfaces of the staple 500 are provided with either a permanent or bioresorbable polymeric coating as described here, and at least the inner surface 540 is provided with a sealant agent coating.

[0086] FIG. 5B is a schematic showing an alternate exemplary surgical staple, as one embodiment of the present disclosure. In FIG. 5B, the staple 500 is composed of at least one fiberoptic fiber 525 and at least one sealant agent containing fiber 530 that are provided in a groove 515 within the underside of the body 505 and legs 510 of the staple 500. A port 520, located on the face 535 of the staple 500 allows exposure of at least one fiberoptic fiber 525 to an externally applied electromagnetic radiation source [not shown in FIG. 5B], such that can illuminate the fiberoptic fiber(s) 525. The surfaces of the staple 500 in Fig. 5B, are provided with a polymeric coating as described here, and at least the inner surface 540 is provided with a sealant agent coating. [0087] FIG. 5C is a schematic showing an exemplary surgical stapling device for use with the surgical staple of FIGS. 5A-B, as one embodiment of the present disclosure. In FIG. 5C, the surgical stapling device 550 comprises a shaft 555 extending from an operator handle 560 to delivery jaws 565 provided to permit an operator to drive a stable into tissue and crimp it in place. The staples in FIGS. 5A-B can be provided for individual delivery, or can be provided in clips for delivery of multiple staples, either sequentially or grouped. The jaws 565 of the surgical stapling device 550 are provided with fiberoptic fibers 575 extending within the shaft 555 an in continuity with a fiber optic cable 580. The surgical stapling device can be connected to an operable radiation source such as an electromagnetic radiation source [not shown in FIG. 5C] to allow irradiation of implanted staples at the time of staple delivery. This radiation exposure initiates the release and activation of the sealant agent coating, which reacts and bonds with the staples of FIGS 5A-B and adjacent tissues.

EXAMPLE 6 [0088] FIG. 6A is a schematic showing an exemplary vascular clip, as one embodiment of the present disclosure. In FIG. 6A, the vascular clip 600 has parallel jaws 605 held in proximity at rest by action of a spring 615, but are capable of opening by operator compression of the release members 610. [0089] FIG. 6B is a cross-sectional perspective of the exemplary vascular clip at the plane of line of A-A' through the jaws of FIG. 6A, as one embodiment of the present disclosure. In FIG. 6B, the jaws are composed of a structural core 602 with an intermediate polymeric coating 604, and outer sealant agent layer 606, The vascular clip from FIG. 6A has a structural core that can be constructed of ferrous or nonferrous metals, metal alloys, plastics, polymers such as L-lactide/giycolide copolymer, poly(lactide-co-giycolide) polymers, other polymers, or combinations thereof.

[0090] FIG. 6C is a schematic showing an exemplary clip applicator for use with the vascular clip of FIG. 6A-B, as one embodiment of the present disclosure. In FIG. 6C, the surgical clip applicator 620 can deliver individual clips, or can deliver multiple dips in a sequential individual manner or in an array of multiple clips simultaneously. The body 650 of the clip applicator can have an operable handle 665 and triggers, 655 and 660. The surgical dip 600 from FIG. 6A-B, can be located within jaws 625 that may attached to a tube 640 operated by either a trigger or handle of the dip applicator. Also, the clip applicator houses fiberoptic fibers 630 in continuity with a fiberoptic cable 670. The fiber optic cable can be connected to a radiation source, such as an electromagnetic radiation source [not shown in FIG. 6C], to allow irradiation of an implanted surgical clip at the time of crimping. This radiation exposure initiates the release and activation of the sealant agent in intermediate sealant agent layer of FIG. 6B, which reacts and bonds with the surgical clip in FIGS. 6A-B and adjacent tissues.

EXAMPLE 7

[0091] FIG. 7A is a schematic showing an exemplary fixation plate, as one embodiment of the present disclosure, In FIG. 7A, a surgical fixation plate 700 is composed of a flattened body 705 perforated by a plurality of countersunk bores 710 to receive fixation screws [not shown in FIG. 7A].

[0092] FIG. 7B is a cross-sectional perspective of the exemplary fixation plate of at plane of line A-A' FIG. 7A, as one embodiment of the present disclosure. In FIG. 7B, a fiberoptic mesh 725, is provided on the surface of the surgical fixation plate of FIG. 7A, with an intermediate sealant agent coating layer 720, and an innermost polymeric coating 715 that covers the plate body 705. The polymeric coating layers may cover all surfaces of the plate body 70S, including the inner surfaces of the countersunk bores 710. After application, an operable radiation source can be used to irradiate all surfaces of the surgical fixation plate 700, via the mesh of fiberoptic fiber (s) 725. This radiation exposure initiates the release and activation of the sealant agent in intermediate sealant agent layer 720, which reacts and bonds with the surgical fixation plate of FIG. 7A and adjacent tissues.

[0093] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention.

However, it will be apparent to one skilled in the art that the specific details are not required in order to practice the invention. The foregoing descriptions of specific embodiments of the present invention are presented for purpose of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Obviously many modifications and variations are possible in view of the above teachings. The embodiments are shown and described in order to best explain the principles of the invention and its practical applications, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the following claims and their equivalent

Claims

We claim:

1. A tissue-fastening article, comprising: a structural member, incorporating and/or encapsulated, partly or entirely, by at least one high molecular weight polyphosphazene polymer of formula (I),

wherein: n is an integer from about 40 to about 100,000; R¹ to R⁶ are independently selected from: a) a substituted or υnsubstituted aflcyl, alkoxy, arγl, aryloxy, silyl, silyloxy, alkylsulfonyl, alkyl amino, dialkyl amino, ureido, carboxylic acid ester, alkyimonoamidine, alkylbisamidine, alkoxymonoamidine, or alkoxybisamidine; or an amino; b) a heterocyclic alkyl group with at least one nitrogen, phosphorus, oxygen, sulfur, or selenium as a heteroatom; c) a heteroaryl group with at least one nitrogen, phosphorus, oxygen, sulfur, or selenium as the heterøatom; d) a nucleotide or a nucleotide residue; e) a biomacromolecule; or f) a pyrimidine or a purine base.

2. The tissue-fastening article of Claim 1 selected from the group consisting of: a surgical fastening device, a suture, a surgical screw, a surgical staple, a vascular clip, a pin, a metal mesh, a bolt, a tack, a hook, a coil, a bracket, a wire, an external fixation device, a suture-anchoring screw, a scaffold, a wound dressing, a rod, and a fixation plate.

3. The tissue-fastening article of Claim i, wherein at least one R¹ to R⁶ sυbstituent is an alkoxy group substituted with at least one fluorine atom.

4. The tissue-fastening article of Claim 1, wherein at least one R¹ to R⁶ substituent is selected from the group consisting of: OCH₃, OCH₂CH₃,

0(Ob)₂CH₃, 0(CH₂)₃CH₃, O(CH₂)₄CH₃, O(CH₂)₅CH₃, OCF₃, OCH₂CF₃, OCH₂CH₂CF₃, OCH₂CF₂CF₃, OCH(CfS)₂, OCCH₃(CF₃)₂, OCH₂CF₂CF₂CF₃, OCH₂(CF₂KF₃, OCH₂(CFa)₄CF₃, OCH₂(CF₂)SCF₃, OCH₂(CF₂)₆CF₃, OCH₂(CFz)₇CF₃, OCH₂CF₂CHF₂, OCH₂CF₂CF₂CHF₂, OCH₂(CF₂)₃CHF₂, OCH₂(CF₂)₄CHF₂, OCH₂(CF₂)₅CHF₂, OCH₂(CF₂)₆CHF₂, and OCH₂(CF₂)τCHF₂.

5. The tissue-fastening article of Claim 1, wherein the R¹ to R⁶ substituent is 1% or less of an alkenoxy group.

6. The tissue-fastening article of Claim i, wherein the polyphosphazene polymer of formula (I) has a molecular weight of at least 2,000,000 g/mol.

7. The tissue-fastening article of Claim 1, wherein the polyphosphazene polymer of formula (I) forms a coating and/or incorporates as component of the structural member.

8. The tissue-fastening article of Claim 1, wherein the polyphosphazene polymer of formula (I) forms a coating over the surface of the structural member.

9. The tissue-fastening article of Claim 1, wherein the structural member is selected from the group consisting of: a conventional suture, a silk, a Nylon, a gut, polyglycolic acid, polyglyconates, polydioxanes (glycoles or lactides), polyesthers, polycaprolactones, polyhydroxybutyrates, po!y(amino acids), glycomer 631, coated braided lactomer, other polymeric materials, stainless steel, other metals and metal alloys, plastics, ceramics, and polymers,

10. The tissue-fastening article of Claim 1 , wherein structural member comprises at least one fiberoptic structural fiber.

11. The tissue-fastening article of Claim 1, wherein the structural member is bioresorbable.

12. The tissue-fastening article of Claim 8 further comprising a sealant agent

13. The tissue-fastening article of Claim 12, wherein the sealant agent is provided as a layer between the structural member and the coating.

14. The tissue-fastening article of Claim 12, wherein the sealant agent is provided as a component of the structural member.

15. The tissue-fastening article of Claim 12, wherein the sealant agent further comprises an adhesion promoter.

16. A method of making the tissue-fastening article of Claim 1, the method comprising: providing a structural member; and applying, to the structural member, one or more high molecular weight polyphosphazene polymer of formula (I) of Claim 1.