Collagen-containing molding blocks

Abstract

The present invention is directed to a dental implant abutment comprising a molded block, an implant, an abutment and a molded block, wherein the molded block comprises a dried collagen matrix, and a method for preparing the same. [Selected Figure] Figure 1

Description

[Technical Field]

[0001] The present invention is directed to a dental implant abutment comprising a molded block, an implant, an abutment and a molded block, wherein the molded block comprises a dry collagen matrix, and a method for preparing the same. [Background technology]

[0002] Gingivitis around dental implants (peri-implant mucositis) often leads to irreversible bone loss (peri-implantitis) and, if not treated properly, can lead to implant loss. It is estimated to affect approximately 30% of all dental implants and is a major concern for patients and physicians.

[0003] One of the many potential etiologies for the development of peri-implantitis is bacterial colonization within the biological width, the minimum distance between the implant margin and the alveolar bone crest. It is often associated with inadequate soft tissue thickness, which has been shown to increase bone resorption after implant-abutment connection. Another widely studied factor is the soft tissue seal around the implant abutment, which is often characterized by the attachment of fibroblasts and epithelial cells to titanium or zirconia. Repeated abutment removal and attachment during the restoration phase of the implant can result in the loss of this important attachment.

[0004] The need to augment and strengthen soft tissue attachment and thickness around dental implants has given rise to several surgical techniques, most of which are based on harvesting dense autologous connective tissue and implanting it next to the implant in the at-risk or esthetic zone. Limited surgical skills restrict these procedures to highly skilled surgeons. Therefore, a solution is needed that involves the use of an effective and easy-to-use medical device. This device must support soft tissue augmentation and allow for the creation and maintenance of biological width.

[0005] The present invention provides a molded block comprising a dry collagen matrix, which can be molded into a variety of shapes, such as an O-ring, and has been shown to form and reinforce a connective tissue seal around a dental implant abutment. Summary of the Invention [Means for solving the problem]

[0006] In one embodiment, the present invention is directed to a shaped block comprising a dry cross-linked collagen matrix. In another embodiment, the dry cross-linked collagen matrix further comprises hydroxyapatite, titanium, a pharmaceutically active agent, or any combination thereof.

[0007] In one embodiment, the present invention is directed to a shaped block for use as an add-on device for a medical device, implant, device attachment, or any combination thereof, wherein the shaped block comprises a dry cross-linked collagen matrix. In another embodiment, the dry cross-linked collagen matrix further comprises hydroxyapatite, titanium, a pharmaceutically active agent, or any combination thereof.

[0008] In one embodiment, the present invention is directed to a dental implant abutment comprising an implant, an abutment, and a molded block comprising a dry cross-linked collagen matrix, the molded block being positioned between the abutment and the implant such that the molded block is in at least partial direct contact with the implant and / or abutment. In another embodiment, the positioning of the molded block within the dental implant abutment allows a foundation for soft / hard tissue ingrowth. In another embodiment, the sliding movement of the molded block between the implant and the abutment bridges the abutment and implant with the molded block, allowing for supported tissue ingrowth to occur.

[0009] In one embodiment, the present invention is directed to a dental implant abutment for use in stimulating bone or soft tissue growth, the dental implant abutment comprising an implant, the abutment, and a shaped block comprising a dry cross-linked collagen matrix, the shaped block being positioned between the abutment and the implant so as to be in at least partial direct contact with the implant, the shaped block of the dental implant abutment being in partial and / or complete contact with the bone and / or soft tissue surrounding said dental implant abutment, and the dental implant abutment of the present invention providing a space and environment for cellular ingrowth.

[0010] In another embodiment, the shaped block is shaped as an O-ring, sleeve, or tube (FIG. 2A).

[0011] In one embodiment, the present invention is directed to a method for preparing a shaped block comprising a dry cross-linked collagen matrix, the method comprising: a. providing a dry cross-linked collagen matrix of the present invention; b. Cutting shaped blocks from the dried matrix.

[0012] In one embodiment, the present invention is directed to a method of preparing a molded block of a dental implant abutment as described herein, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, a molded block of the dental implant abutment described above is obtained.

[0013] In one embodiment, the present invention is directed to a method of preparing a molded block of a dental implant abutment as described herein, the method comprising: (i) providing an acidic solution of collagen and a crosslinker, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, a molded block of the dental implant abutment described above is obtained.

[0014] In one embodiment, the present invention is directed to a method of preparing a molded block of a dental implant abutment as described herein, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a cross-linking agent and a first solvent; (v) optionally adding a pharmaceutically active agent to the incubated composition of step (iv) and washing the resulting solution with a second solvent; (vi) lyophilizing the washed composition of step (v); Thereby, a molded block of the dental implant abutment described above is obtained. [Brief explanation of the drawings]

[0015] The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of this specification. However, the invention, both as to organization and method of operation, together with its objects, features, and advantages, may best be understood by reference to the following detailed description when read in connection with the accompanying drawings.

[0016] [Figure 1] 1 shows a dental implant abutment of the present invention, including an implant, an abutment and a molding block indicated by arrows. [Figure 2A] 1 is a diagram of the shape of a molded block of the present invention. [Figure 2B] 1 is a shaped block prepared in accordance with an embodiment of the present invention.

[0017] It will be understood that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. DETAILED DESCRIPTION OF THE INVENTION

[0018] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention.

[0019] Molded blocks and uses thereof

[0020] In one aspect, the invention provides a shaped block comprising a dry collagen matrix. In one embodiment, the dry collagen matrix comprises cross-linked collagen. In one embodiment, the invention provides a shaped block comprising a dry cross-linked collagen matrix. In another embodiment, the dry cross-linked collagen matrix further comprises hydroxyapatite, titanium, a pharmaceutically active agent, or any combination thereof.

[0021] In another embodiment, the present invention provides a shaped block for use as an add-on element / unit for a medical device, implant, device attachment, or any combination thereof, wherein the shaped block comprises a dry cross-linked collagen matrix.

[0022] In another embodiment, the molded block is used as an add-on element / unit for a medical device. In another embodiment, the molded block is used as an add-on element / unit for an implant. In another embodiment, the molded block is used as an add-on element / unit for a device attachment. In another embodiment, any medical device known in the art can be used. In another embodiment, the implant is a dental implant body. In another embodiment, any dental implant body known in the art can be used. In another embodiment, non-limiting examples of device attachments include prostheses, molded screws, molded plates, molded wires, or any other attachment for bone / jaw reconstruction. Each possibility represents a separate embodiment of the present invention.

[0023] In some embodiments, the term "add-on element / unit" refers to a shaped physical product that can be added to other known apparatus, devices, or products. In other embodiments, the addition is performed by one skilled in the art of the present invention. In other embodiments, the addition includes the following non-limiting actions: placing the additional element / unit on or adjacent to the other device; chemically manipulating them to provide a solid connection therebetween (e.g., welding, melting and solidifying, dissolving and precipitating); mechanically manipulating them (e.g., screwing, scraping); and any combination thereof. In another embodiment, the additional unit / element is a shaped block of the present invention that is added to a dental implant abutment, wire, plate, screw, or clamp, or any device, apparatus, or product known in the art. Each possibility represents a separate embodiment of the present invention.

[0024] In some embodiments, the term "block" refers to a physical extent of a solid. In other embodiments, the solid is dry and does not contain any solvents or liquids. In other embodiments, the solid comprises at least one single component. In another embodiment, non-limiting examples of components include compounds, small molecules, metals, alloys, composites, biomaterials, polymers, and organometallic complexes. In another embodiment, the solid comprises two or more components selected from the foregoing list. In another embodiment, the block comprises a biocompatible material or composition. In another embodiment, the block is a biopolymer or protein. In another embodiment, the physical attributes of the block allow it to be designed, molded, cut, or engineered into a desired shape as known in the art. In another embodiment, non-limiting examples of block attributes include the following properties: dense, porous or non-porous, viscous, rigid, soft, or moldable. In another embodiment, the block has a porosity of 10-90%. In another embodiment, the block has a porosity of 10-20%. In another embodiment, the block has a porosity of 20-30%. In another embodiment, the block has a porosity of 30-40%. In another embodiment, the block has a porosity of 40-50%. In another embodiment, the block has a porosity of 50-60%. In another embodiment, the block has a porosity of 60-70%. In another embodiment, the block has a porosity of 70-80%. In another embodiment, the block has a porosity of 80-90%. In another embodiment, the block has a porosity of 10-30%. In another embodiment, the block has a porosity of 30-50%. In another embodiment, the block has a porosity of 50-70%. In another embodiment, the block has a porosity of 70-90%. Each possibility represents a separate embodiment of the present invention.

[0025] In some embodiments, the term "shaped block" refers to a block that is provided in any shape or form, i.e., that is designed, engineered, manufactured, or prepared as known in the art to provide the two- or three-dimensional structure of such block. In other embodiments, non-limiting examples of two- or three-dimensional structures include squares, circles, triangles, O-rings, sleeves, tubes, pyramids, boxes, cuboids, cylinders, cones, prisms, and any other structure that includes a hole therein. In other embodiments, any possible design, engineering, manufacturing, or preparation process can be applied to provide the shaped block.

[0026] In some embodiments, the term "collagen" refers to a biological macromolecule organized in a fibrous network or other non-fibrillar superstructure, which is the major component of connective tissue in the human or many animal body. Many types of collagen are known and found in nature. A non-limiting example includes type IV. In some embodiments, collagen has a fibrillar (such as type I) or non-fibrillar structure. Each possibility represents a separate embodiment of the present invention.

[0027] In one embodiment, the collagen used in the methods, uses, and shaped blocks of the present invention includes native collagen, fibrillar collagen, fibrillar atelopeptide collagen, lyophilized collagen, collagen obtained from animal sources, human collagen, recombinant collagen, pepsinized collagen, reconstituted collagen, and any combination thereof. In another embodiment, the collagen includes fibrillar collagen reconstituted from monomolecular atelopeptide collagen. In another embodiment, the collagen is atelopeptide fibrillar collagen obtained by reconstituting monomolecular atelopeptide collagen obtained by proteolysis of native collagen. Each possibility represents a separate embodiment of the present invention.

[0028] In some embodiments, the term "crosslinked collagen" refers to a covalent network comprising biopolymer chains of collagen covalently and intermolecularly bonded with a crosslinking agent.

[0029] In some embodiments, the term "crosslinker" refers to a small molecule or polymer that contains at least two termini that are capable of covalently linking polymeric / oligomeric chains, thereby crosslinking those chains.

[0030] In some embodiments, the collagen is cross-linked by a sugar. In other embodiments, the sugar is selected from the group consisting of glycerol (glyceraldehyde), threose, erythrose, lyxose, xylose, arabinose, ribose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, and any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0031] In another embodiment, the sugar is a disaccharide.Each possibility represents a separate embodiment of the present invention.

[0032] In another embodiment, the disaccharide is selected from the group consisting of maltose, lactose, sucrose, cellobiose, gentiobiose, melibiose, turanose, trehalose, and any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0033] In another aspect, the present invention provides a dental implant abutment (FIG. 1) comprising an implant, an abutment, and a molded block as described herein. In one embodiment, the present invention provides a dental implant abutment comprising an implant, an abutment, and a molded block comprising a dry cross-linked collagen matrix, the molded block being positioned between the abutment and the implant such that the molded block is in at least partial contact with the implant and / or abutment. In another embodiment, the positioning of the molded block within the dental implant abutment allows a foundation for soft / hard tissue ingrowth. In another embodiment, the sliding movement of the molded block between the implant and abutment bridges the abutment and implant with the molded block, allowing supported tissue ingrowth to occur. In another embodiment, the molded block of the dental implant abutment is in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment.

[0034] In another embodiment, the implant is in partial contact with the molded block. In another embodiment, the implant is completely covered by the molded block. In one embodiment, the implant of any of the dental implant abutments of the present invention can be utilized, provided, or fabricated in any manner known in the art. In another embodiment, the implant is made from a material including a polymer, a ceramic, a metal (e.g., Ti, Zr), or an alloy, or any combination thereof. In another embodiment, the shape / size of the implant includes a cone, a cylinder, a plate, a wire thread, a shape including holes, or any combination thereof. In one embodiment, the abutment of any of the dental implant abutments of the present invention can be utilized, provided, or fabricated in any manner known in the art. In another embodiment, the abutment is made from a material including a polymer, a ceramic, a metal (e.g., Ti, Zr), or an alloy, or any combination thereof. In another embodiment, the shape / size of the abutment includes a cylinder, a cone, a cube, or any combination thereof. In some embodiments, non-limiting examples of polymers for the abutment and / or implant include polyurethane, polymethyl methacrylate, polysiloxane, polylactic acid, polyacrylamide, any combination thereof, and any other biocompatible polymer. In some embodiments, non-limiting examples of ceramics for the abutment and / or implant include zirconia, alumina, titania, calcium phosphate, any combination thereof, and any other biocompatible ceramic. In some embodiments, non-limiting examples of metals or alloys for the abutment and / or implant include Ti, Zr, Ni, NiTi, any combination thereof, and any other biocompatible metal or alloy. Each possibility represents a separate embodiment of the present invention.

[0035] In yet another aspect, the dental implant abutment of the present invention is used to stimulate bone or soft tissue growth. In one embodiment, the dental implant abutment of the present invention provides a space and environment for cellular ingrowth. The soft yet conformable nature of the material allows for a tight fit between the abutment and the implant surface, and the surrounding soft and bony tissue. This proximity, combined with the conductive properties of bone and soft tissue, allows for the abutment to be quickly and effectively incorporated.

[0036] In another embodiment, the shaped block further comprises hydroxyapatite, titanium, a pharmaceutically active agent, or any combination thereof.

[0037] In other embodiments, non-limiting examples of pharmaceutically active agents include antibacterial agents, antifungal agents, antiseptics, anti-inflammatory agents, antibiotics, vitamins, or any combination thereof. In another embodiment, any agent within the foregoing list known in the art can be utilized. Each possibility represents a separate embodiment of the present invention.

[0038] In other embodiments, non-limiting examples of active agents include antibacterial agents, antifungal agents, antiseptics, anti-inflammatory agents, antibiotics, vitamins and vitamers, and any combination thereof. In another embodiment, any agent within the foregoing list known in the art can be utilized. Each possibility represents a separate embodiment of the present invention.

[0039] In another embodiment, non-limiting examples of antibacterial agents include amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, arbekacin, plazomycin, streptomycin, apramycin, geldanamycin, herbimycin, loracarbef, faropenem, ertapenem, doripenem, imipenem, meropenem, cefazolin, cephacetrile, cefadroxil, cephalexin, cephaloglycin, cephalonium, cephaloridine, cephalothin, cephapirin, cefatrizine, cefazed. cefazaflur, cephradine, cefroxadine, cefazole, cefaclor, cefamandole, cefminox, cefonicid, ceforanide, cefotiam, cefprozil, cefbuperazone, cefuroxime, cefuzonam, cephamycin, cefoxitin, cefotetan, cefmetazole, carbacephem, cefixime, ceftazidime, ceftriaxone, cefcapene, cefdaloxime, cefdinir, cefditoren, cefetamet, cefmenoxime, cefodizime, cefperazone, cefotaxime, cefpimizole, cefpiramide, cefpo Doxime, cefsulodin, cefteram, ceftibuten, ceftiolene, ceftizoxime, oxacephem, cefepime, cefozofur, cefpirome, cefquinome, ceftiofur, cefquinome, cefovecin, CXA-101, ceftaroline, ceftobiprole, clindamycin, lincomycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, spectinomycin, solithromycin, aztreonam, furazolidone, nitrofurantoin, amoxicillin Cillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, temocillin, ticarcillin, iprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidizic acid, levonadifloxacin, norfloxacin, ofloxacin, trovafloxacin, grepafloxacin, sparfloxacin, temafloxacin, delafloxacin,These include mafenide, sulfonamide chrysoidine, sulfacetamide, sulfadiazine, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfisoxazole, trimethoprim, emeclocycline, doxycycline, minocycline, oxytetracycline, tetracycline, tigecycline, tedizolid, linezolid, lambezolid, torezolid, radezolid, any combination thereof, and any pharmaceutically acceptable salt thereof. Each possibility represents a separate embodiment of the present invention.

[0040] In another embodiment, non-limiting examples of antifungal agents include terbinafine, naftifine, amphotericin B, butenafine, chloroxylenol, ciclopirox, flucytosine, caspofungin, griseofulvin, clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, oxiconazole, nystatin, undecylenic acid, any combination thereof, and any pharmaceutically acceptable salt thereof. Each possibility represents a separate embodiment of the present invention.

[0041] In another embodiment, non-limiting examples of preservatives include naftifine, tolnaftate, mediocidin, candicidin, trichomycin, hamycin, aurefungin, ascosin, aifatin, azacortin, trichomycin, levorin, heptamycin, candimycin, griseofulvin, pradimicin, benanomicin, ambisome, nikkomycin Z, flucytosine, perimycin, any combination thereof, and a pharmaceutically acceptable salt of any of these. Each possibility represents a separate embodiment of the present invention.

[0042] In another embodiment, non-limiting examples of anti-inflammatory agents include aspirin, ibuprofen, naproxen, celecoxib, diclofenac, ketoprofen, ketorolac, oxaprozin, salsalate, sulindac, any combination thereof, and pharmaceutically acceptable salts of any of these. Each possibility represents a separate embodiment of the present invention.

[0043] In another embodiment, non-limiting examples of antibiotics include penicillin, cephalosporin, ciprofloxacin, erythromycin, any combination thereof, and pharmaceutically acceptable salts of any of these. Each possibility represents a separate embodiment of the present invention.

[0044] In another embodiment, non-limiting examples of vitamins include vitamin A, retinol, retinal, carotenoids, vitamin B1, thiamine, vitamin B2, riboflavin, vitamin B3, niacin, niacinamide, nicotinamide, riboside, vitamin B5, pantothenic acid, vitamin B6, pyridoxine, pyridoxamine, pyridoxal, vitamin B7, biotin, vitamin B9, folic acid, vitamin B12, cyanocobalamin, hydrocobalamin, methylcobalamin, adenosylcobalamin, vitamin C, ascorbic acid, vitamin D, cholecalciferol (D3), ergocalciferol (D2), vitamin E, tocopherol, tocotrienol, vitamin K, phylloquinone, menaquinone, any combination thereof, and pharmaceutically acceptable salts of any of these. Each possibility represents a separate embodiment of the present invention.

[0045] In some embodiments, the term "hydroxyapatite" refers to Ca(PO)(OH) or Ca 10 Hydroxyapatite refers to a naturally occurring calcium mineral having the formula (PO4)6(OH)2. In other embodiments, hydroxyapatite can be prepared or obtained using any method known in the art. In another embodiment, bulk or nanoparticulate hydroxyapatite is utilized and / or prepared. Each possibility represents a separate embodiment of the present invention.

[0046] In some embodiments, the term "titanium" refers to titanium metal or alloys. In other embodiments, the titanium is alloyed with non-limiting examples of Zr and / or Ni. In another embodiment, the titanium is biocompatible. In another embodiment, the titanium is a biocompatible titanium alloy. In another embodiment, the titanium metal is in any shape or form known in the art. In another embodiment, the titanium or alloyed titanium can have shape memory capabilities. In another embodiment, the shape or form of the titanium metal includes bulk metal, its surface, or nanoparticles. In another embodiment, the bulk metal is formed into a rod, plate, cube, or any other physical shape known in the art. Each possibility represents a separate embodiment of the present invention.

[0047] In some embodiments, the term "nanoparticulate material" (e.g., hydroxyapatite or titanium) refers to a material having at least one physical nanometer dimension. In other embodiments, the nanoparticulate material is shaped as a nanoparticle, nanosphere, nanocube, nanoplate, nanoribbon, nanowire, nanorod, or any other nanometric shape, as known in the art.

[0048] Methods for preparing shaped blocks of the present invention

[0049] In a further aspect, the present invention is directed to a method for preparing a shaped block comprising the dry cross-linked collagen matrix of the present invention, the method comprising: a. providing a dry cross-linked collagen matrix of the present invention; b. Cutting shaped blocks from the dried matrix.

[0050] In another embodiment, the dry cross-linked collagen matrix comprises hydroxyapatite. In another embodiment, the dry cross-linked collagen matrix comprises titanium. In another embodiment, the cross-linked collagen matrix comprises a pharmaceutically active agent. In another embodiment, the dry cross-linked collagen matrix comprises hydroxyapatite, titanium, a pharmaceutically active agent, or any combination thereof.

[0051] In one embodiment, the present invention is directed to a method for preparing a dry cross-linked collagen matrix, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i); (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition; (iv) incubating the composition with a cross-linking agent and a first solvent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, the dry cross-linked collagen matrix of the present invention is obtained.

[0052] In one embodiment, the present invention is directed to a method of preparing a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, and optionally hydroxyapatite, titanium, a pharmaceutically active agent, or any combination thereof, the method comprising: (i) providing an acidic solution of collagen followed by neutralizing the solution, the neutralized solution optionally comprising hydroxyapatite; (ii) concentrating the solution of step (i) and optionally adding titanium; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition; (iv) incubating the composition with a crosslinker, a first solvent, and optionally adding a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, the dry cross-linked collagen matrix of the present invention is obtained.

[0053] In one embodiment, the present invention relates to a method for preparing a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen and hydroxyapatite, the method comprising: (i) providing an acidic solution of collagen followed by neutralizing the solution, the neutralized solution comprising hydroxyapatite; (ii) concentrating the solution of step (i); (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition; (iv) incubating the composition with a cross-linking agent and a first solvent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, the dry cross-linked collagen matrix of the present invention is obtained.

[0054] In one embodiment, the present invention relates to a method for preparing a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen and a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i); (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition; (iv) incubating the composition with a crosslinker, a first solvent, and a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, the dry cross-linked collagen matrix of the present invention is obtained.

[0055] In one embodiment, the present invention relates to a method for preparing a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, titanium, and a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and adding titanium; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition; (iv) incubating the composition with a crosslinker, a first solvent, and a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, the dry cross-linked collagen matrix of the present invention is obtained.

[0056] In another embodiment, in addition to or instead of the freeze-drying step, a compression step (applying mechanical pressure using specialized equipment) is applied.

[0057] In some embodiments, cutting is performed by any method known in the art. In another embodiment, cutting in the method of the present invention is performed by a CNC (computer numerical control) machine, a laser cutting machine, a water jet High pressure This can be done by a jet cutter, a punch, or a grinding device, with each possibility representing a separate embodiment of the present invention.

[0058] In some embodiments, the shaped blocks of the present invention are provided in a variety of shapes. In some embodiments, the blocks are shaped to allow for easy attachment of the blocks onto a dental abutment and to at least partially cover the dental implant when the abutment is placed on the implant. In other embodiments, the blocks are shaped as O-rings, sleeves, or tubes. Each possibility represents a separate embodiment of the present invention.

[0059] Method for preparing molded blocks of the present invention using a mold

[0060] In a further aspect, the present invention is directed to a method for preparing a shaped block comprising a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, optionally hydroxyapatite, and optionally a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, a shaped block of the invention is obtained.In another embodiment, the neutralization solution of step (i) optionally comprises hydroxyapatite.

[0061] In one embodiment, the present invention is directed to a method of preparing a shaped block comprising a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, optionally hydroxyapatite, and optionally a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen and a crosslinker, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, a shaped block of the invention is obtained.In another embodiment, the neutralization solution of step (i) optionally comprises hydroxyapatite.

[0062] In one embodiment, the present invention is directed to a method of preparing a shaped block comprising a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, optionally hydroxyapatite, and optionally a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen, followed by neutralizing the solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a cross-linking agent and a first solvent; (v) optionally adding a pharmaceutically active agent to the incubated composition of step (iv) and washing the resulting solution with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, a shaped block of the invention is obtained.In another embodiment, the neutralization solution of step (i) optionally comprises hydroxyapatite.

[0063] In one embodiment, the present invention is directed to a method of preparing a shaped block comprising a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, optionally hydroxyapatite, optionally titanium, and optionally a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen followed by neutralizing the solution, the neutralized solution optionally comprising hydroxyapatite; (ii) concentrating the solution of step (i), optionally adding titanium, and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), Thereby, the molded block of the present invention is obtained.

[0064] In another embodiment, in addition to or instead of the freeze-drying step, a compression step (applying mechanical pressure using specialized equipment) is applied.

[0065] In another embodiment, the mold is cooled to a freezing temperature of between -10°C and -190°C prior to the freeze-drying step (iii). In another embodiment, the mold is cooled to a freezing temperature of between -10°C and -80°C for 0.5 to 24 hours, followed by the freeze-drying step (iii). In another embodiment, cooling is carried out for 0.5 to 24 hours. In another embodiment, cooling is carried out for 0.5 to 1 hour. In another embodiment, cooling is carried out for 1 to 2 hours. In another embodiment, cooling is carried out for 2 to 5 hours. In another embodiment, cooling is carried out for 5 to 10 hours. In another embodiment, cooling is carried out for 10 to 24 hours. Each possibility represents a separate embodiment of the present invention.

[0066] In another embodiment, the desired block shape is formed using methods including molding, 3D printing, cast molding, or any combination thereof, with each possibility representing a separate embodiment of the present invention.

[0067] Method for preparing the molded block of the present invention using the granulated material

[0068] In one embodiment, the present invention is directed to a method of preparing a shaped block comprising a dry cross-linked collagen matrix, the matrix comprising cross-linked collagen, optionally hydroxyapatite, optionally titanium, and optionally a pharmaceutically active agent, the method comprising: (i) providing an acidic solution of collagen followed by neutralizing the solution, the neutralized solution optionally comprising hydroxyapatite; (ii) concentrating the solution of step (i) and optionally adding titanium; (iii) incubating the composition with a crosslinker, a first solvent, and optionally adding a pharmaceutically active agent; (iv) washing the incubated composition of step (iv) with a second solvent; (v) homogenizing, casting, and milling the composition to obtain a granulation of cross-linked collagen; (vi) wetting the granulation of step (v) with the first or second solvent and cutting to obtain the shaped blocks of the present invention.

[0069] In some embodiments, the molded blocks and / or dried cross-linked collagen matrices produced using the methods of the present invention as described above are used in and / or are part of the dental implant abutments of the present invention as also described above.

[0070] In some embodiments, the shaped block or blocks obtained by the methods of the present invention are milled to form a granulation, which is then wetted with a first or second solvent and cut to obtain a shaped block comprising a crosslinked collagen matrix. In another embodiment, the size of the granulation is between 1 and 2000 microns.

[0071] In some embodiments, the collagen used in the methods of the invention in the solution of step "(i)" is selected from the following non-limiting examples, including native collagen, fibrillar collagen, fibrillar atelopeptide collagen, lyophilized collagen, collagen obtained from an animal source, human collagen, recombinant collagen, pepsinized collagen, reconstituted collagen, and any combination thereof. In another embodiment, the collagen comprises fibrillar collagen reconstituted from monomolecular atelopeptide collagen. In another embodiment, the collagen is atelopeptide fibrillar collagen obtained by reconstituting monomolecular atelopeptide collagen obtained by proteolysis of native collagen. Each possibility represents a separate embodiment of the invention.

[0072] In another embodiment, the neutralization solution comprises a base or buffer. In another embodiment, the neutralization solution further comprises hydroxyapatite. In another embodiment, the buffer is selected from phosphate buffered saline, NaHCO3 / Na2CO3 buffer, Tris or Tricine buffer, or any other buffer that maintains a neutral pH. In another embodiment, the acidic solution comprises HCl, acetic acid, nitric acid, citric acid, sulfuric acid, phosphoric acid, or any other acid known in the art. In another embodiment, the basic solution comprises NaOH, KOH, NaHCO3, Na2CO 3、 Na2HPO4 or any other base known in the art.

[0073] In some embodiments, the term "neutral pH" refers to a pH range similar to physiological pH in an organism and / or system, and is defined as between 6.5 and 7.5. In some other embodiments, a neutral pH is between 6.5 and 6.7. In some other embodiments, a neutral pH is between 6.7 and 6.9. In some other embodiments, a neutral pH is between 6.9 and 7.1. In some other embodiments, a neutral pH is between 7.1 and 7.3. In some other embodiments, a neutral pH is between 7.3 and 7.5. In some other embodiments, a neutral pH is between 7.1 and 7.2. In some other embodiments, a neutral pH is between 7.2 and 7.3. In some other embodiments, a neutral pH is between 7.3 and 7.4. In some other embodiments, a neutral pH is between 7.4 and 7.5.

[0074] In one embodiment, the concentration step is carried out by centrifugation. In another embodiment, the centrifugation is carried out at a speed of 50 to 20,000 RPM (revolutions per minute). In another embodiment, the centrifugation is carried out at a speed of between 50 and 100 RPM. In another embodiment, the centrifugation is carried out at a speed of between 100 and 1,000 RPM. In another embodiment, the centrifugation is carried out at a speed of between 1,000 and 5,000 RPM. In another embodiment, the centrifugation is carried out at a speed of between 5,000 and 10,000 RPM. In another embodiment, the centrifugation is carried out at a speed of between 10,000 and 20,000 RPM. In another embodiment, the centrifugation is carried out for 1 to 120 minutes. In another embodiment, the centrifugation is carried out for 1 to 5 minutes. In another embodiment, the centrifugation is carried out for 5 to 10 minutes. In another embodiment, the centrifugation is carried out for 10 to 20 minutes. In another embodiment, the centrifugation is carried out for 20 to 50 minutes. In another embodiment, the centrifugation is carried out for 50 to 100 minutes. In another embodiment, centrifugation is performed for 100-120 minutes. Each possibility represents a separate embodiment of the present invention.

[0075] In another embodiment, the lyophilization in step (iii) is carried out for 1 to 48 hours. In another embodiment, the lyophilization in step (iii) is carried out for 1 to 2 hours. In another embodiment, the lyophilization in step (iii) is carried out for 2 to 5 hours. In another embodiment, the lyophilization in step (iii) is carried out for 5 to 10 hours. In another embodiment, the lyophilization in step (iii) is carried out for 10 to 24 hours. In another embodiment, the lyophilization in step (iii) is carried out for 24 to 48 hours. Each possibility represents a separate embodiment of the present invention.

[0076] After freeze-drying, the dry collagen composition of the present invention is obtained. The dried composition is incubated with a cross-linking agent, a first solvent, and optionally a pharmaceutically active agent. The incubated composition is further washed with a second solvent and freeze-dried to obtain a block collagen composition.

[0077] In another embodiment, the first and second solvents are the same or different and are selected from any solvent known in the art, hi another embodiment, the solvent is selected from the group including water, ethanol, saline, methanol, phosphate buffered saline, or any combination thereof.

[0078] In another embodiment, the cross-linking agent can be any cross-linking agent known in the art. In another embodiment, the cross-linking agent is a sugar. In another embodiment, the sugar is a compound represented by at least one of the following chemical formulas (I) or (II):

[0079] [ka]

[0080] During the ceremony, R 1 is H or alkyl or alkenyl, an amino acid moiety, a peptide moiety, a saccharide moiety, a purine or pyrimidine moiety, a phosphorylated purine or pyrimidine moiety, n is an integer from 2 to 9, p and q are each independently an integer of 0 to 8, and the sum of p and q is at least 2 and 8 or less.

[0081] In another embodiment, the term "alkyl" refers to a saturated aliphatic hydrocarbon, including straight or branched chains. In one embodiment, an alkyl group is straight or branched chain. In another embodiment, an alkyl is optionally substituted straight or branched chain. In one embodiment, an alkyl group has 1 to 20 carbons. In one embodiment, an alkyl group has 1 to 10 carbons. In one embodiment, an alkyl group has 2 to 10 carbons. In one embodiment, an alkyl group has 1 to 6 carbons. In one embodiment, an alkyl group has 2 to 8 carbons. In another embodiment, non-limiting examples of alkyl groups include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, pentyl, 3-pentyl, hexylheptyl, octyl, and hexadecyl. In another embodiment, an alkyl group is optionally substituted with one or more halogen, hydroxide, alkoxide, carboxylic acid, phosphate, phosphonate, sulfate, sulfonate amidate, cyanate, and nitro groups. Each possibility represents a separate embodiment of the present invention.

[0082] In another embodiment, the term "alkenyl" refers to an alkyl group, as described herein, having at least one carbon-carbon double bond, including straight-chain and branched-chain groups. In one embodiment, the alkene has one double bond. In another embodiment, the alkene has two or more double bonds. In another embodiment, the alkene has two to six double bonds, with each possibility representing a separate embodiment of the present invention. In one embodiment, the alkene has two to twenty carbons. Non-limiting examples include ethylenyl, propylenyl, 2-methylpropyl-1-enyl, and butenyl, with each possibility representing a separate embodiment of the present invention.

[0083] In another embodiment, the term "amino acid" refers to an organic compound containing an amine (-NH2) and a carboxyl (-COOH) functional group, along with a side chain characteristic of each amino acid. In another embodiment, any amino acid known in the art can be utilized. In another embodiment, the amino acid is alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, or valine.

[0084] In another embodiment, the term "peptide" refers to a short chain of amino acids covalently linked through amide (-C(O)-N(H)-) bonds. In another embodiment, a peptide comprises 2-20 amino acids. In another embodiment, a peptide is a dipeptide. In another embodiment, a peptide is a tripeptide. In another embodiment, a peptide is a tetrapeptide. In another embodiment, a peptide is a pentapeptide. In another embodiment, a peptide is a hexapeptide.

[0085] In another embodiment, the term "saccharide" refers to a group that includes sugars, cellulose, and starches, as described herein.

[0086] In another embodiment, the term "purine" refers to a heterocyclic aromatic organic compound consisting of a pyrimidine ring fused to an imidazole ring. Non-limiting examples of purines include purine, adenine, guanine, hypoxanthine, xanthine, theobromine, caffeine, uric acid, and isoguanine.

[0087] In another embodiment, the term "pyrimidine" refers to a heterocyclic aromatic organic compound similar to pyridine, but with an additional nitrogen in the aromatic ring, such that the nitrogen is found at positions 1 and 3 of the ring. Non-limiting examples of purines include cytosine, thymine, and uracil.

[0088] In another embodiment, the term "phosphorylated purine or pyrimidine" refers to a purine or pyrimidine as described herein, wherein the purine or pyrimidine is linked to a phosphoryl group (chemical entity PO3 x- , "x" denotes any possible protonation state).

[0089] In another embodiment, the sugar is a naturally occurring reducing sugar.

[0090] In alternative embodiments, the sugar is a diose, triose, tetrose, pentose, hexose, septose, octose, nanose, or decose. Each possibility represents a separate embodiment of the present invention.

[0091] In another embodiment, the sugar is selected from the group consisting of glycerol (glyceraldehyde), threose, erythrose, lyxose, xylose, arabinose, ribose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, and any combination thereof, with each possibility representing a separate embodiment of the present invention.

[0092] In another embodiment, the sugar is a disaccharide.Each possibility represents a separate embodiment of the present invention.

[0093] In another embodiment, the disaccharide is selected from the group consisting of maltose, lactose, sucrose, cellobiose, gentiobiose, melibiose, turanose, trehalose, and any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0094] Following the crosslinking and washing steps with the first and second solutions, the composition is freeze-dried. In another embodiment, the freeze-drying in step (vi) is carried out for 24 to 72 hours to obtain a block composition. In one embodiment, the block collagen composition is prepared using a mold having a pre-designed shape, thereby obtaining a block-shaped collagen composition. In another embodiment, no mold is used, and a block collagen composition is obtained, which is further cut into the desired block-shaped collagen composition.

[0095] In some other embodiments, the designed mold and cutouts are planned, designed, and / or engineered using computer-aided design (CAD) and / or computer-aided manufacturing (CAM) methods and software known in the art, with each possibility representing a separate embodiment of the present invention.

[0096] In another embodiment, the cutting of the method of the present invention is performed by any method known in the art. In another embodiment, the cutting of the method of the present invention is performed by a CNC (computer numerical control) machine, a laser cutting machine, a water jet High pressure This can be done by a jet cutter, a punch, or a grinding device, with each possibility representing a separate embodiment of the present invention.

[0097] In some embodiments, the shaped blocks of the present invention are provided in a variety of shapes. In some embodiments, the blocks are shaped to allow for easy attachment of the blocks onto a dental abutment and to at least partially cover the dental implant when the abutment is placed on the implant. In other embodiments, the blocks are shaped as O-rings, sleeves, or tubes (FIG. 2A). Each possibility represents a separate embodiment of the present invention.

[0098] The following examples are presented in order to more fully illustrate the preferred embodiments of the invention, but they should in no way be construed as limiting the broad scope of the invention.

[0099] Example

[0100] Example 1

[0101] Collagen cross-linking A solution of molecularly purified pepsinized porcine type I collagen (1–10 mg / milliliter) prepared from porcine tendons (commercially available from Pel-Freez, AR, USA) was dissolved in 0.01 M HCl and maintained at 4 °C. The solution was neutralized to pH 7.2–7.4 with 0.1 M NaOH, poured into a suitable mold, and incubated at temperatures ranging from 20–38 °C for 24 hours. The resulting matrix was then compressed with a piston to remove excess solution. The resulting collagen membrane was then incubated in PBS for 11 days.

[0102] The fibrillated collagen was concentrated by centrifugation at 3000 rpm. All centrifugations (unless otherwise specified) were performed using a model RC5C centrifuge equipped with a SORVALL SS-34 rotor, available from SORVALL® Instruments DUPONT, USA. The fibrillated collagen concentration after centrifugation was approximately 35 mg / mL using 10 mM phosphate buffer (PBS pH 7.36). The mixture was poured into a stainless steel tray. The tray was transferred to a freeze dryer (freeze dryer model FD8, available from Heto Lab Equipment DK-3450 Allerod, Denmark), pre-frozen for 8 hours, and freeze-dried for 24 hours. The condenser temperature was -80°C. The shelf temperature during pre-freezing was -40°C. The shelf temperature during freeze-drying was +35°C, and the vacuum during freeze-drying was approximately 0.01 bar.

[0103] A 200 mL solution containing 120 mL of absolute ethanol (commercially available from Merck, Germany), 80 mL of PBS buffer (10 mM, pH 7.36), and 3 grams of D(-)ribose (commercially available from Sigma, USA, catalog no. R7500) was added to the dried (lyophilized) fibrillated collagen and incubated at 37°C for 11 days to allow ribose cross-linking of the collagen structure. Using the same conditions as above, the ribose-cross-linked collagen product was thoroughly washed with DI water and lyophilized.

[0104] Example 2

[0105] Collagen-hydroxyapatite cross-linking

[0106] The purified collagen solution consisted of atelocollagen monomer [pepsinized type I collagen (~3 mg / mL)] dissolved in 0.05 M acetic acid, maintained at 4 °C, and mixed with a 0.1 M NaOH slurry containing hydroxyapatite (collagen / HA ratio: 95:5 to 70:30) to neutral pH. The solution was then incubated at temperatures ranging from 20 to 37 °C for 24 h with constant stirring. The fibrillated collagen / HA mixture was concentrated by centrifugation at 3000 rpm for 15 min. The fibrillated collagen concentration after centrifugation was approximately 35 mg / mL using 10 mM phosphate buffer (PBS pH 7.36). The mixture was then homogenized for 10 min at 100 rpm using a planetary centrifugal mixer ("THINKY MIXER" ARE-500, THINKY CORPORATION, Japan) poured into a stainless steel tray. The trays were transferred to a freeze dryer (freeze dryer model FD8, commercially available from Heto Lab Equipment DK-3450 Allerod, Denmark), pre-frozen for 8 hours, and freeze-dried for 24 hours. The condenser temperature was -80°C. The shelf temperature during pre-freezing was -40°C. The shelf temperature during freeze-drying was +35°C, and the vacuum during freeze-drying was approximately 0.01 bar.

[0107] A 200 mL solution containing 120 mL of absolute ethanol (commercially available from Merck, Germany), 80 mL of PBS buffer (10 mM, pH 7.36), and 3 grams of DL-glyceraldehyde (commercially available from Biosynth, Switzerland) was added to the dried (lyophilized) fibrillated collagen and incubated at 37°C for 11 days to allow ribose cross-linking of the collagen structure. Using the same conditions as above, the ribose-cross-linked collagen product was thoroughly washed with DI water and lyophilized.

[0108] Example 3

[0109] Collagen block cutting

[0110] Blocks of dried collagen matrix are used to cut out the desired shapes. These shapes can have an O-ring appearance, or they can be sleeve- or tube-like (Figure 2b). These structures fit easily over the abutment and, once the abutment is placed on the implant, they partially or completely cover the implant.

[0111] The flexible yet conforming nature of the material allows for a close fit to the abutment and implant surfaces, and to the surrounding soft and bony tissue. This proximity, combined with the conductive properties of bone and soft tissue, allows for fast and effective integration of the abutment.

[0112] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims

1. 1. A dental implant abutment, comprising: an implant; an abutment; and a molding block, the shaped block consists essentially of a dry cross-linked collagen matrix; the shaped block is positioned between the abutment and the implant so as to be in direct contact at least partially with the implant and / or the abutment; A dental implant abutment, wherein the shape of the molded block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted.

2. 1. A dental implant abutment for use in stimulating bone or soft tissue growth, comprising: The dental implant abutment includes an implant, an abutment, and a molding block; the shaped block consists essentially of a dry cross-linked collagen matrix; the shaped block is positioned between the abutment and the implant so as to be in direct contact at least partially with the implant and / or the abutment; the shape of the shaped block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted; A dental implant abutment, wherein the flexible yet conforming nature of the dry cross-linked collagen matrix provides a tight fit to the surface of the abutment and implant, and to the surrounding soft and bony tissue, allowing the dry cross-linked collagen matrix to interact with the surrounding tissue, thereby providing space and an environment for cellular ingrowth when the dental implant abutment is implanted.

3. 1. A dental implant abutment for use in stimulating bone or soft tissue growth, comprising: The dental implant abutment includes an implant, an abutment, and a molding block; the shaped block essentially comprises a dry cross-linked collagen matrix and hydroxyapatite; the shaped block is positioned between the abutment and the implant so as to be in direct contact at least partially with the implant and / or the abutment; the shape of the shaped block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted; A dental implant abutment, wherein the flexible yet conforming nature of the dry cross-linked collagen matrix provides a tight fit to the surface of the abutment and implant, and to the surrounding soft and bony tissue, allowing the dry cross-linked collagen matrix to interact with the surrounding tissue, thereby providing space and an environment for cellular ingrowth when the dental implant abutment is implanted.

4. 1. A dental implant abutment for use in stimulating bone or soft tissue growth, comprising: The dental implant abutment includes an implant, an abutment, and a molding block; the shaped block essentially comprises a dry cross-linked collagen matrix and titanium; the shaped block is positioned between the abutment and the implant so as to be in direct contact at least partially with the implant and / or the abutment; the shaped block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted; A dental implant abutment, wherein the flexible yet conforming nature of the dry cross-linked collagen matrix provides a tight fit to the surface of the abutment and implant, and to the surrounding soft and bony tissue, allowing the dry cross-linked collagen matrix to interact with the surrounding tissue, thereby providing space and an environment for cellular ingrowth when the dental implant abutment is implanted.

5. The dental implant abutment according to any one of claims 1 to 4, wherein the molded block has an O-ring-like, sleeve-like, or tube-like shape.

6. 1. A dental implant abutment, comprising: an implant; an abutment; and a molding block, said shaped block consisting essentially of a dry cross-linked collagen matrix and a pharmaceutically active agent; the shaped block is positioned between the abutment and the implant so as to be in direct contact at least partially with the implant and / or the abutment; A dental implant abutment, wherein the shape of the molded block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted.

7. The dental implant abutment of claim 6 , wherein the pharmaceutically active agent comprises an antibacterial agent, an antifungal agent, an anti-inflammatory agent, an antibiotic, a vitamin, or any combination thereof.

8. 1. A dental implant abutment, comprising: an implant; an abutment; and a molding block, the shaped block consists essentially of a dry cross-linked collagen matrix; the molded block is positioned to extend circumferentially around the abutment-implant interface so as to be in direct contact with at least a portion of the implant and with the abutment; A dental implant abutment, wherein the shape of the molded block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted.

9. 1. A dental implant abutment for use in stimulating bone or soft tissue growth, comprising: The dental implant abutment includes an implant, an abutment, and a molding block; the shaped block consists essentially of a dry cross-linked collagen matrix; the molding block is positioned to extend circumferentially around the joint between the abutment and the implant so as to be in direct contact at least partially with the implant and with the abutment; the shape of the shaped block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted; A dental implant abutment, wherein the flexible yet conforming nature of the dry cross-linked collagen matrix provides a tight fit to the surface of the abutment and implant, and to the surrounding soft and bony tissue, allowing the dry cross-linked collagen matrix to interact with the surrounding tissue, thereby providing space and an environment for cellular ingrowth when the dental implant abutment is implanted.

10. 1. A dental implant abutment for use in stimulating bone or soft tissue growth, comprising: The dental implant abutment includes an implant, an abutment, and a molding block; the shaped block essentially comprises a dry cross-linked collagen matrix and hydroxyapatite; the molding block is positioned to extend circumferentially around the joint between the abutment and the implant so as to be in direct contact at least in part with the implant and / or the abutment; the shaped block is configured so that when implanted, the dental implant abutment is in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment; A dental implant abutment, wherein the flexible yet conforming nature of the dry cross-linked collagen matrix provides a tight fit to the surface of the abutment and implant, and to the surrounding soft and bony tissue, allowing the dry cross-linked collagen matrix to interact with the surrounding tissue, thereby providing space and an environment for cellular ingrowth when the dental implant abutment is implanted.

11. 1. A dental implant abutment for use in stimulating bone or soft tissue growth, comprising: The dental implant abutment includes an implant, an abutment, and a molding block; the shaped block essentially comprises a dry cross-linked collagen matrix and titanium; the molding block is positioned to extend circumferentially around the joint between the abutment and the implant so as to be in direct contact at least in part with the implant and / or the abutment; the shaped block is configured so that when implanted, the dental implant abutment is in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment; A dental implant abutment, wherein the flexible yet conforming nature of the dry cross-linked collagen matrix provides a tight fit to the surface of the abutment and implant, and to the surrounding soft and bony tissue, allowing the dry cross-linked collagen matrix to interact with the surrounding tissue, thereby providing space and an environment for cellular ingrowth when the dental implant abutment is implanted.

12. The dental implant abutment according to any one of claims 8 to 11, wherein the molded block has an O-ring-like, sleeve-like or tube-like shape.

13. 1. A dental implant abutment, comprising: an implant; an abutment; and a molding block, said shaped block consisting essentially of a dry cross-linked collagen matrix and a pharmaceutically active agent; the molding block is positioned to extend circumferentially around the joint between the abutment and the implant so as to be in direct contact at least in part with the implant and / or the abutment; A dental implant abutment, wherein the shape of the molded block allows the dental implant abutment to be in partial and / or complete contact with the bone and / or soft tissue surrounding the dental implant abutment when implanted.

14. 14. The dental implant abutment of claim 13, wherein the pharmaceutically active agent comprises an antibacterial agent, an antifungal agent, an anti-inflammatory agent, an antibiotic, a vitamin, or any combination thereof.

15. A method for manufacturing a molded block of a dental implant abutment according to any one of claims 1 to 14, comprising the steps of: a. providing the dry cross-linked collagen matrix; b. cutting a shaped block from said dried cross-linked collagen matrix.

16. the dry cross-linked collagen matrix (i) providing an acidic solution of collagen followed by neutralizing said solution; (ii) concentrating the solution of step (i); (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition; (iv) incubating the composition with a cross-linking agent and a first solvent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v); The method of claim 15, whereby a dry cross-linked collagen matrix is ​​obtained.

17. A method for preparing a molded block of a dental implant abutment according to any one of claims 1 to 14, said method comprising: (i) providing an acidic solution of collagen followed by neutralizing said solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition, optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), A method whereby a molded block of a dental implant abutment according to any one of claims 1 to 14 is obtained.

18. A method for preparing a molded block of a dental implant abutment according to any one of claims 1 to 14, said method comprising: (i) providing an acidic solution of collagen followed by neutralizing said solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition, optionally containing hydroxyapatite; (iv) incubating the composition with a crosslinker, a first solvent, and optionally a pharmaceutically active agent; (v) washing the incubated composition of step (iv) with a second solvent; (vi) lyophilizing the washed composition of step (v), A method whereby a molded block of a dental implant abutment according to any one of claims 1 to 14 is obtained.

19. A method for preparing a molded block of a dental implant abutment according to any one of claims 1 to 14, said method comprising: (i) providing an acidic solution of collagen followed by neutralizing said solution; (ii) concentrating the solution of step (i) and pouring it into a mold having a pre-designed block shape; (iii) freeze-drying the concentrated mixture of step (ii), thereby obtaining a dry collagen composition, optionally containing hydroxyapatite; (iv) incubating the composition with a cross-linking agent and a first solvent; (v) optionally adding a pharmaceutically active agent to the incubated composition of step (iv) and washing the resulting solution with a second solvent; (vi) lyophilizing the washed composition of step (v), A method whereby a molded block of a dental implant abutment according to any one of claims 1 to 14 is obtained.

20. The method according to any one of claims 15 to 19, wherein the obtained shaped block has an O-ring-like, sleeve-like or tubular shape.

21. 17. The method of claim 15 or 16, wherein the cutting out is performed by a CNC machine, a laser cutting machine, a water jet high pressure jet cutter, a drilling machine, a grinding device, or by using a mould or a 3D printer during the manufacturing process.

22. 20. The method of any one of claims 17 to 19, wherein the mold is formed using a method comprising 3D printing, cast molding, or any combination thereof.

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