[go: up one dir, main page]

US20190135696A1 - Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects - Google Patents

Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects Download PDF

Info

Publication number
US20190135696A1
US20190135696A1 US16/125,199 US201816125199A US2019135696A1 US 20190135696 A1 US20190135696 A1 US 20190135696A1 US 201816125199 A US201816125199 A US 201816125199A US 2019135696 A1 US2019135696 A1 US 2019135696A1
Authority
US
United States
Prior art keywords
calcium sulfate
graft material
bone graft
bone
compressive strength
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US16/125,199
Inventor
Jantzen A. Cole
Michael E. Carroll
Jon P. Moseley
Kelly C. Richelsoph
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wright Medical Technology Inc
Original Assignee
Wright Medical Technology Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wright Medical Technology Inc filed Critical Wright Medical Technology Inc
Priority to US16/125,199 priority Critical patent/US20190135696A1/en
Publication of US20190135696A1 publication Critical patent/US20190135696A1/en
Assigned to WRIGHT MEDICAL TECHNOLOGY, INC. reassignment WRIGHT MEDICAL TECHNOLOGY, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MOSELEY, JON P., COLE, JANTZEN A., CARROLL, MICHAEL E., RICHELSOPH, KELLY C.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/14—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing calcium sulfate cements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/10—Ceramics or glasses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B2017/00004—(bio)absorbable, (bio)resorbable or resorptive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A61F2002/2835—Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006—Properties of materials and coating materials
    • A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00034—Physico-chemical characteristics of the mixtures
    • C04B2111/00146—Sprayable or pumpable mixtures
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
    • C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications

Definitions

  • the present application pertains to bone graft materials and, more particularly, to resorbable bone graft materials optimized for strength, injection and osteoconductivity and to methods of strengthening bones using injectable, resorbable bone graft materials.
  • Minimally invasive surgical procedures have become very popular in the orthopedic field; and accordingly, it has become desirable to be able to inject invasive surgical procedures have become very popular in the orthopedic field; and accordingly, it has become desirable to be able to inject bone graft materials in a minimally invasive manner, such as via a syringe. Since it is desirable for some bone graft materials set or cure in the body, time constraints are an issue in that the bone graft materials must maintain sufficiently low viscosity to allow injection without requiring substantial ejection force but, after injection, should, desirably, cure quickly to provide compression strength as soon as possible. Additionally, it is preferred that bone graft materials be resorbable (bioabsorbable), as opposed to bone cement which is not, and osteoconductive.
  • the MIIG® 115 injectable bone graft material described in US Published Patent Application 2003/0185903 and marketed by Wright Medical Technology, Inc., the assignee of the present invention, is an effective injectable resorbable bone graft material made from calcium sulfate hemihydrate; however, improvements are desirable relating to working time (the time period available in which the bone graft material can be implanted in the body), injectability (the relative force required to easily inject the bone graft material through associated instrumentation using hand and/or thumb force), the set or cure time relative to compressive strength, the compressive strength achieved one hour after injection and the compressive strength achieved 24 hours after injection.
  • working time the time period available in which the bone graft material can be implanted in the body
  • injectability the relative force required to easily inject the bone graft material through associated instrumentation using hand and/or thumb force
  • the set or cure time relative to compressive strength the compressive strength achieved one hour after injection and the compressive strength achieved 24 hours after injection.
  • Calcium sulfate hemihydrate for use as bone graft materials have, in the past, been made using hydrothermal processes where calcium sulfate dihydrate is boiled in a reaction vessel under greater than atmospheric pressure and result in a structure which requires an undesirable amount of water for hydration.
  • the present invention provides a high strength, injectable resorbable bone graft material for treating bone defects by implanting or injecting the injectable resorbable bone graft material therein.
  • bone defects as used herein includes, but is not limited to, defects or voids/gaps resulting from compression fractures, benign bone cysts, diseased bone, high energy trauma, peri-articular fractures, cranial-maxillo facial fractures, osteoporotic reinforcement (i.e., screw augmentation), joint arthrodesis, joint arthroplasty and periodontal reconstruction.
  • the injectable resorbable bone graft material of the present invention is particularly useful for minimally invasive insertion in bone defects to provide a temporary support media as well as a resorbable graft, the bone graft material being osteoconductive and replaced by bone.
  • the injectable bone graft material according to the present invention permits injection up to 5 minutes after mixing of calcium sulfate hemihydrate powder, with or without an accelerant, with a diluent to produce a paste, the paste achieving, within 10 minutes after injection, a compressive strength of cancellous bone, within 20 minutes after injection, achieving a compressive strength of at least the upper end of cancellous bone, and, within 24 hours after injection, achieving a compressive strength well above cancellous bone.
  • FIG. 1 is a scanning electron micrograph (SEM) depicting the crystalline structure of the calcium sulfate hemihydrate used in the present invention and in particular how it is formed of thick, stubby rod-like crystals prior to milling.
  • SEM scanning electron micrograph
  • FIG. 2 is a scanning electron micrograph (SEM) depicting the crystalline structure of the calcium sulfate hemihydrate used in the present invention and in particular how it is formed of thick, stubby rod-like crystals after milling.
  • SEM scanning electron micrograph
  • a powder composed of calcium sulfate hemihydrate, in a range from 99.8% to 100% and, if the calcium sulfate hemihydrate is less that 100%, an accelerant (or accelerator), preferably calcium sulfate dihydrate, up to 0.20% may be added.
  • the powder, calcium sulfate hemihydrate or a blend including the accelerant is mixed with a diluent, such as sterile water, prior to insertion (or implant) in bone, the diluent to powder weight ratio range being from 0.19:1 to 0.31:1.
  • the calcium sulfate hemihydrate is made by a known process, as disclosed in U.S. Pat. No.
  • calcium sulfate dihydrate is immersed in a solution of water and an inorganic salt, such as magnesium chloride, calcium chloride, sodium chloride or other biocompatible inorganic salts selected from ammonium chloride, ammonium bromide, ammonium iodide, ammonium nitrate, ammonium sulfate, calcium bromide, calcium iodide, calcium nitrate, magnesium bromide, magnesium iodide, magnesium nitrate, sodium bromide, sodium iodide, sodium nitrate, potassium chloride, potassium bromide, potassium iodide, potassium nitrate, caesium chloride, caesium nitrate, caesium sulfate, zinc chloride, zinc bromide, zinc iodide, zinc nitrate, zinc sulfate, cupric chloride, cupric bromide, cupric nitrate, cupric chloride, cupric bromide, cupric nitrate,
  • the calcium sulfate dihydrate and the solution are heated to substantially the boiling point at atmospheric pressure until a substantial portion of the calcium sulfate dihydrate is converted to calcium sulfate hemihydrate.
  • the resulting calcium sulfate hemihydrate has a different crystalline structure than calcium sulfate hemihydrate produced by hydrothermal processes and has a lower water-carrying capacity after being milled ( FIG. 2 ) according to conventional methods as described in the patent, but for in vivo orthopeadic applications.
  • the crystalline structure of the calcium sulfate hemihydrate used in the present invention is formed of thick, stubby rod-like crystals, as disclosed in U.S. Pat. No. 2,616,789 (FIG. 1).
  • the powder with the diluent forms a paste that is intended to be injected into bone defects, as defined above, that are not intrinsic to the stability of bony structure of the skeletal system (i.e., the extremities, spine, and pelvis) and to cure in situ.
  • the bone defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.
  • the paste provides a bone void filler that resorbs and is replaced with bone during the healing process.
  • the injectable resorbable bone graft material paste cured in situ provides an open void/gap filler that augments provisional hardware (e.g., K-Wires) to help support bone fragments during surgical procedures.
  • the cured paste acts only as a temporary support media and is not intended to provide structural support during the healing process.
  • needles are pre-placed in defects under fluoroscopic guidance.
  • the plunger is removed from a syringe and set aside.
  • the powder and sterile water are placed in a bowl and mixed, preferably in a vacuum mixer.
  • the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg.
  • the bowl should be tapped to keep the paste in the mixing zone.
  • a spatula is used to transfer the paste to the syringe.
  • the plunger is replaced, the syringe is inverted, and the plunger is advanced to remove air.
  • the syringe is then docked to a pre-placed needle, and injection is initiated with steady thumb pressure.
  • the total injection time should be approximately 2.5 minutes.
  • the calcium sulfate hemihydrate has low water-carrying capacity and is formed of thick, stubby rod-like crystals, as disclosed in U.S. Pat. No. 2,616,789.
  • Such calcium sulfate hemihydrate has not been used, prior to the present invention, as a bone graft or substitute material.
  • such calcium sulfate hemihydrate allows optimizing of action times and compressive strength as well as being resorbable, that is absorbable in the body within a time required to permit bone defect healing.
  • a working time of 5 minutes or greater, depending on the amount of diluent or accelerant added, can be achieved to permit the injectable resorbable bone graft paste to be loaded into the syringe and to be injected into the bone, e.g. via the syringe and pre-placed needle.
  • the injectable resorbable bone graft material sets or cures quickly in the body to provide improved compressive strengths from prior art bone graft materials.
  • the accelerant is believed to enhance, e.g., accelerate, the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate.
  • particles of the accelerant act as crystallization nucleation sites for the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate.
  • accelerants include calcium sulfate dihydrate, potassium sulfate and sodium sulfate.
  • Other examples include ionic salts.
  • a preferred accelerant is calcium sulfate dihydrate crystals (available from U.S. Gypsum) coated with sucrose (available from VWR Scientific Products). A process of stabilizing the dihydrate crystals by coating with sucrose is described in U.S. Pat. No. 3,573,947, hereby incorporated by reference in its entirety. Mixtures of two or more accelerants can be used.
  • the diluent is generally selected to provide the composition with a desired consistency and hardening time.
  • diluent include water, e.g., sterile water, solutions containing inorganic salts, or cationic surface active agents including sodium chloride, saline, e.g., phosphate buffered saline, potassium chloride, sodium sulfate, potassium sulfate, EDTA, ammonium sulfate, ammonium acetate, and sodium acetate.
  • saline e.g., phosphate buffered saline
  • potassium chloride sodium sulfate, potassium sulfate, EDTA
  • ammonium sulfate ammonium acetate
  • sodium acetate e.g., sodium sulfate
  • EDTA e.g., sodium sulfate
  • ammonium sulfate ammonium acetate
  • sodium acetate e.g.
  • the diluent can further include, for example, bone marrow aspirate, platelet concentrate, blood, pharmaceutical additives in solution, or combinations of these materials.
  • additives are medicaments or pesticides.
  • medicaments are antibiotics, chemotherapeutic agents, growth factors, and analgesics.
  • antibiotics are tetracycline hydrochloride, vancomycin, cephalosporins, and aminoglygocides such as tobramycin and gentamicin.
  • chemotherapeutic agents are cis-platinum, ifosfamide, methotrexate, and doxorubicin hydrochloride (Adriamycin®).
  • growth factors are transforming growth factors beta (TGF-Beta), bone morphogenic protein (BMP), basic fiberblast growth factor, platelet-derived growth factor, and other polypeptide growth factors.
  • TGF-Beta transforming growth factors beta
  • BMP bone morphogenic protein
  • basic fiberblast growth factor basic fiberblast growth factor
  • platelet-derived growth factor platelet-derived growth factor
  • analgesics are anesthetics such as lidocaine hydrochloride (Xylocaine®), bipvacaine hydrochloride (Marcaine®), and non-steroidal anti-inflammatory drugs such as keterolac tromethamine (Toradol®).
  • the present invention produces an injectable resorbable bone graft material for minimally invasive implant in a bone defect utilizing a powder comprising calcium sulfate hemihydrate mixable with a diluent in a diluent to powder weight ratio from 0.19:1 to 0.31:1 to form an injectable paste and utilizing a powder formed of calcium sulfate hemihydrate and an accelerant, and a diluent mixed with the powder, the calcium sulfate hemihydrate forming, by weight, from 99.8% to 100% of the powder, the accelerant forming, by weight, from 0% to 0.2% of the powder, and the diluent to powder weight ratio being from 0.19:1 to 0.31:1.
  • the accelerant is calcium sulfate dihydrate and the diluent is sterile water, the calcium sulfate hemihydrate forms 99.99% of the powder by weight, the calcium sulfate dihydrate forms 0.01% of the powder by weight and the sterile water to powder weight ratio is 0.25:1.
  • the present invention includes treating bone defects by injecting a resorbable bone graft material in the form of a paste by mixing calcium sulfate hemihydrate having thick stubby rod-like crystals with water.
  • the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg.
  • the resulting paste is placed into a syringe and can be injected through a 6 cm long, 11-gauge needle.
  • cylindrical samples (6 mm in diameter, 12 mm high) can be formed for compressive strength testing.
  • the specimens are allowed to cure at atmospheric pressure (no pressure applied to curing specimens) in air at approximately 21 deg C. for 1 hour and 24 hours then subjected to compression tests. This is known as dry-testing.
  • 35-grams mixture of 99.995% calcium sulfate hemihydrate powder manufactured as described above and placed into a bowl with about 6.65 g of water and the two are mixed (water-to-powder ratio 0.19), preferably in a vacuum mixer.
  • the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg.
  • the resulting paste is placed into a syringe and can be injected through a 6 cm long, 11-gauge needle.
  • cylindrical samples (6 mm in diameter, 12 mm high) can be formed for compressive strength testing. The specimens are allowed to cure at atmospheric pressure (no pressure applied to curing specimens) in air at approximately 21 deg C. for 1 hour and 24 hours then subjected to compression tests. This is the dry-test.
  • 35-grams mixture of 99.995% calcium sulfate hemihydrate powder manufactured as described above and placed into a bowl with about 8.05 g of water and the two are mixed (water-to-powder ratio 0.23), preferably in a vacuum mixer.
  • the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg.
  • the resulting paste is placed into a syringe and can be injected through a 6 cm long, 11-gauge needle.
  • cylindrical samples (6 mm in diameter, 12 mm high) can be formed for compressive strength testing. The specimens are allowed to cure at atmospheric pressure (no pressure applied to curing specimens) in bovine serum at 37° C.
  • wet-testing the results from this mode of testing are believed to be more indicative of the type of results that would result from the actual in vivo use of the material.
  • dry-testing results are correlated to wet-testing results, in the sense that the higher the compressive strength obtained in the dry-test, the higher the compressive strength that can be expected through the wet-test.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Ceramic Engineering (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Structural Engineering (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

An injectable resorbable bone graft material, and methods of using the same, provide increased compressive strength after injection in a bone defect. The bone graft material is made from calcium sulfate hemihydrate having a thick stubby rod-like crystalline structure and low water-carrying capacity.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • The present application is a continuation application of U.S. application Ser. No. 10/772,108, filed Feb. 4, 2004, which claims the benefit of U.S. Provisional Application No. 60/444,690, filed Feb. 4, 2003; the contents of which are herein incorporated by reference in their entirety.
    • BACKGROUND OF THE INVENTION Field of the Invention
  • The present application pertains to bone graft materials and, more particularly, to resorbable bone graft materials optimized for strength, injection and osteoconductivity and to methods of strengthening bones using injectable, resorbable bone graft materials.
    • Brief Discussion of the Related Art
  • Minimally invasive surgical procedures have become very popular in the orthopedic field; and accordingly, it has become desirable to be able to inject invasive surgical procedures have become very popular in the orthopedic field; and accordingly, it has become desirable to be able to inject bone graft materials in a minimally invasive manner, such as via a syringe. Since it is desirable for some bone graft materials set or cure in the body, time constraints are an issue in that the bone graft materials must maintain sufficiently low viscosity to allow injection without requiring substantial ejection force but, after injection, should, desirably, cure quickly to provide compression strength as soon as possible. Additionally, it is preferred that bone graft materials be resorbable (bioabsorbable), as opposed to bone cement which is not, and osteoconductive. The MIIG® 115 injectable bone graft material, described in US Published Patent Application 2003/0185903 and marketed by Wright Medical Technology, Inc., the assignee of the present invention, is an effective injectable resorbable bone graft material made from calcium sulfate hemihydrate; however, improvements are desirable relating to working time (the time period available in which the bone graft material can be implanted in the body), injectability (the relative force required to easily inject the bone graft material through associated instrumentation using hand and/or thumb force), the set or cure time relative to compressive strength, the compressive strength achieved one hour after injection and the compressive strength achieved 24 hours after injection. Calcium sulfate hemihydrate for use as bone graft materials have, in the past, been made using hydrothermal processes where calcium sulfate dihydrate is boiled in a reaction vessel under greater than atmospheric pressure and result in a structure which requires an undesirable amount of water for hydration.
    • SUMMARY OF THE INVENTION
  • The present invention provides a high strength, injectable resorbable bone graft material for treating bone defects by implanting or injecting the injectable resorbable bone graft material therein. The term “bone defects” as used herein includes, but is not limited to, defects or voids/gaps resulting from compression fractures, benign bone cysts, diseased bone, high energy trauma, peri-articular fractures, cranial-maxillo facial fractures, osteoporotic reinforcement (i.e., screw augmentation), joint arthrodesis, joint arthroplasty and periodontal reconstruction.
  • The injectable resorbable bone graft material of the present invention is particularly useful for minimally invasive insertion in bone defects to provide a temporary support media as well as a resorbable graft, the bone graft material being osteoconductive and replaced by bone.
  • The injectable bone graft material according to the present invention permits injection up to 5 minutes after mixing of calcium sulfate hemihydrate powder, with or without an accelerant, with a diluent to produce a paste, the paste achieving, within 10 minutes after injection, a compressive strength of cancellous bone, within 20 minutes after injection, achieving a compressive strength of at least the upper end of cancellous bone, and, within 24 hours after injection, achieving a compressive strength well above cancellous bone.
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a scanning electron micrograph (SEM) depicting the crystalline structure of the calcium sulfate hemihydrate used in the present invention and in particular how it is formed of thick, stubby rod-like crystals prior to milling.
  • FIG. 2 is a scanning electron micrograph (SEM) depicting the crystalline structure of the calcium sulfate hemihydrate used in the present invention and in particular how it is formed of thick, stubby rod-like crystals after milling.
    •  DESCRIPTION OF THE PREFERRED EMBODIMENT
  • In accordance with the present invention, a powder is provided composed of calcium sulfate hemihydrate, in a range from 99.8% to 100% and, if the calcium sulfate hemihydrate is less that 100%, an accelerant (or accelerator), preferably calcium sulfate dihydrate, up to 0.20% may be added. The powder, calcium sulfate hemihydrate or a blend including the accelerant, is mixed with a diluent, such as sterile water, prior to insertion (or implant) in bone, the diluent to powder weight ratio range being from 0.19:1 to 0.31:1. The calcium sulfate hemihydrate is made by a known process, as disclosed in U.S. Pat. No. 2,616,789, whose contents are incorporated entirely herein by reference, where calcium sulfate dihydrate is immersed in a solution of water and an inorganic salt, such as magnesium chloride, calcium chloride, sodium chloride or other biocompatible inorganic salts selected from ammonium chloride, ammonium bromide, ammonium iodide, ammonium nitrate, ammonium sulfate, calcium bromide, calcium iodide, calcium nitrate, magnesium bromide, magnesium iodide, magnesium nitrate, sodium bromide, sodium iodide, sodium nitrate, potassium chloride, potassium bromide, potassium iodide, potassium nitrate, caesium chloride, caesium nitrate, caesium sulfate, zinc chloride, zinc bromide, zinc iodide, zinc nitrate, zinc sulfate, cupric chloride, cupric bromide, cupric nitrate, cupric sulfate alone or together. The calcium sulfate dihydrate and the solution are heated to substantially the boiling point at atmospheric pressure until a substantial portion of the calcium sulfate dihydrate is converted to calcium sulfate hemihydrate. The resulting calcium sulfate hemihydrate has a different crystalline structure than calcium sulfate hemihydrate produced by hydrothermal processes and has a lower water-carrying capacity after being milled (FIG. 2) according to conventional methods as described in the patent, but for in vivo orthopeadic applications. In particular, the crystalline structure of the calcium sulfate hemihydrate used in the present invention is formed of thick, stubby rod-like crystals, as disclosed in U.S. Pat. No. 2,616,789 (FIG. 1).
  • Mixing of the powder with the diluent forms a paste that is intended to be injected into bone defects, as defined above, that are not intrinsic to the stability of bony structure of the skeletal system (i.e., the extremities, spine, and pelvis) and to cure in situ. The bone defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. The paste provides a bone void filler that resorbs and is replaced with bone during the healing process. The injectable resorbable bone graft material paste cured in situ provides an open void/gap filler that augments provisional hardware (e.g., K-Wires) to help support bone fragments during surgical procedures. The cured paste acts only as a temporary support media and is not intended to provide structural support during the healing process. In use, needles are pre-placed in defects under fluoroscopic guidance. The plunger is removed from a syringe and set aside. The powder and sterile water are placed in a bowl and mixed, preferably in a vacuum mixer. Preferably, the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg. While mixing, the bowl should be tapped to keep the paste in the mixing zone. After mixing, a spatula is used to transfer the paste to the syringe. After the plunger is replaced, the syringe is inverted, and the plunger is advanced to remove air. The syringe is then docked to a pre-placed needle, and injection is initiated with steady thumb pressure. The total injection time should be approximately 2.5 minutes.
  • As noted above the calcium sulfate hemihydrate has low water-carrying capacity and is formed of thick, stubby rod-like crystals, as disclosed in U.S. Pat. No. 2,616,789. Such calcium sulfate hemihydrate has not been used, prior to the present invention, as a bone graft or substitute material. Unexpectedly, such calcium sulfate hemihydrate allows optimizing of action times and compressive strength as well as being resorbable, that is absorbable in the body within a time required to permit bone defect healing.
  • In accordance with the present invention, after mixing, a working time of 5 minutes or greater, depending on the amount of diluent or accelerant added, can be achieved to permit the injectable resorbable bone graft paste to be loaded into the syringe and to be injected into the bone, e.g. via the syringe and pre-placed needle. At the same time, the injectable resorbable bone graft material sets or cures quickly in the body to provide improved compressive strengths from prior art bone graft materials.
  • The accelerant is believed to enhance, e.g., accelerate, the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate. In particular, it is believed that particles of the accelerant act as crystallization nucleation sites for the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate. Examples of accelerants include calcium sulfate dihydrate, potassium sulfate and sodium sulfate. Other examples include ionic salts. A preferred accelerant is calcium sulfate dihydrate crystals (available from U.S. Gypsum) coated with sucrose (available from VWR Scientific Products). A process of stabilizing the dihydrate crystals by coating with sucrose is described in U.S. Pat. No. 3,573,947, hereby incorporated by reference in its entirety. Mixtures of two or more accelerants can be used.
  • The diluent is generally selected to provide the composition with a desired consistency and hardening time. Examples of diluent include water, e.g., sterile water, solutions containing inorganic salts, or cationic surface active agents including sodium chloride, saline, e.g., phosphate buffered saline, potassium chloride, sodium sulfate, potassium sulfate, EDTA, ammonium sulfate, ammonium acetate, and sodium acetate. Mixtures of two or more diluents can be used.
  • The diluent can further include, for example, bone marrow aspirate, platelet concentrate, blood, pharmaceutical additives in solution, or combinations of these materials. Examples of additives are medicaments or pesticides. Examples of medicaments are antibiotics, chemotherapeutic agents, growth factors, and analgesics. Examples of antibiotics are tetracycline hydrochloride, vancomycin, cephalosporins, and aminoglygocides such as tobramycin and gentamicin. Examples of chemotherapeutic agents are cis-platinum, ifosfamide, methotrexate, and doxorubicin hydrochloride (Adriamycin®). Examples of growth factors are transforming growth factors beta (TGF-Beta), bone morphogenic protein (BMP), basic fiberblast growth factor, platelet-derived growth factor, and other polypeptide growth factors. Examples of analgesics are anesthetics such as lidocaine hydrochloride (Xylocaine®), bipvacaine hydrochloride (Marcaine®), and non-steroidal anti-inflammatory drugs such as keterolac tromethamine (Toradol®).
  • As will be appreciated from the foregoing, the present invention produces an injectable resorbable bone graft material for minimally invasive implant in a bone defect utilizing a powder comprising calcium sulfate hemihydrate mixable with a diluent in a diluent to powder weight ratio from 0.19:1 to 0.31:1 to form an injectable paste and utilizing a powder formed of calcium sulfate hemihydrate and an accelerant, and a diluent mixed with the powder, the calcium sulfate hemihydrate forming, by weight, from 99.8% to 100% of the powder, the accelerant forming, by weight, from 0% to 0.2% of the powder, and the diluent to powder weight ratio being from 0.19:1 to 0.31:1. In a specific example, the accelerant is calcium sulfate dihydrate and the diluent is sterile water, the calcium sulfate hemihydrate forms 99.99% of the powder by weight, the calcium sulfate dihydrate forms 0.01% of the powder by weight and the sterile water to powder weight ratio is 0.25:1. Additionally the present invention includes treating bone defects by injecting a resorbable bone graft material in the form of a paste by mixing calcium sulfate hemihydrate having thick stubby rod-like crystals with water.
  • The following examples show the efficacy of the inventive materials and methods according to the invention.
    • Example One
  • A 35-gram mixture of powder having 99.995% calcium sulfate hemihydrate manufactured as described above and 0.005% calcium sulfate dihydrate is placed into a bowl with about 8.75 g of water and the two are mixed (water-to-powder ratio=0.25), preferably in a vacuum mixer. Preferably the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg. The resulting paste is placed into a syringe and can be injected through a 6 cm long, 11-gauge needle. Following procedures similar to ASTM-F451, cylindrical samples (6 mm in diameter, 12 mm high) can be formed for compressive strength testing. The specimens are allowed to cure at atmospheric pressure (no pressure applied to curing specimens) in air at approximately 21 deg C. for 1 hour and 24 hours then subjected to compression tests. This is known as dry-testing.
    • Example Two
  • 35-grams mixture of 99.995% calcium sulfate hemihydrate powder manufactured as described above and placed into a bowl with about 6.65 g of water and the two are mixed (water-to-powder ratio=0.19), preferably in a vacuum mixer. Preferably the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg. The resulting paste is placed into a syringe and can be injected through a 6 cm long, 11-gauge needle. Following procedures similar to ASTM-F451, cylindrical samples (6 mm in diameter, 12 mm high) can be formed for compressive strength testing. The specimens are allowed to cure at atmospheric pressure (no pressure applied to curing specimens) in air at approximately 21 deg C. for 1 hour and 24 hours then subjected to compression tests. This is the dry-test.
    • Example Three
  • 35-grams mixture of 99.995% calcium sulfate hemihydrate powder manufactured as described above and placed into a bowl with about 8.05 g of water and the two are mixed (water-to-powder ratio=0.23), preferably in a vacuum mixer. Preferably the calcium sulfate paste is mixed in one direction for 30 seconds at a vacuum of approximately 22-25 mmHg. The resulting paste is placed into a syringe and can be injected through a 6 cm long, 11-gauge needle. Following procedures similar to ASTM-F451, cylindrical samples (6 mm in diameter, 12 mm high) can be formed for compressive strength testing. The specimens are allowed to cure at atmospheric pressure (no pressure applied to curing specimens) in bovine serum at 37° C. for 1 hour and 24 hours then subjected to compression tests. This is known as wet-testing and the results from this mode of testing are believed to be more indicative of the type of results that would result from the actual in vivo use of the material. However, the dry-testing results are correlated to wet-testing results, in the sense that the higher the compressive strength obtained in the dry-test, the higher the compressive strength that can be expected through the wet-test.
    • Results
  • Mean Compressive Maximum Compressive
    Example Set Time Strength (MPa) Strength (MPa)
    One (dry) 1 hour ≈45 ≈50
    One (dry) 24 hours ≈88 ≈98
    Two (dry) 1 hour ≈49 ≈54
    Two (dry) 24 hours ≈98 ≈106
    Three (wet) 1 hour ≈49 ≈52
    Three (wet) 24 hours ≈56 ≈59
  • After initial testing of similar samples using the same protocols, compressive strengths of 15 MPa (@ 1 hour) 35 MPa (@ 24 hours) were reported in U.S. Provisional Patent Application Ser. No. 60/444,690. The current test results exceed those early test results. As testing and mixing protocols improve, it is foreseen that the various compressive strengths produced by the invention will further increase. Accordingly, the disclosed examples are merely exemplary and not meant to be limiting.

Claims (21)

1. A method for treating bone defects comprising the steps of:
mixing a powder comprising calcium sulfate hemihydrate with a diluent to produce a bone graft material in the form of a paste; and
applying the bone graft material to a bone defect, the bone graft material having a compressive strength in excess of 15 MPa within one hour after said applying step.
2. The method of claim 1, wherein the bone graft material has a compressive strength of approximately 45-49 MPa within one hour after said applying step.
3. The method of claim 1, wherein the bone graft material has a compressive strength exceeding approximately 50 MPa within one hour after said applying step.
4. The method of claim 1, wherein the bone graft material has a compressive strength of at least 6 MPa within 20 minutes after said applying step.
5. The method of claim 1, wherein the bone graft material has a compressive strength of at least 35 MPa within 24 hours after said injecting step.
6. The method of claim 5, wherein the bone graft material has a compressive strength of approximately 56 MPa within 24 hours after said injecting step.
7. The method of claim 1, wherein the diluent is water or a solution comprising an inorganic salt or a cationic surface active agent.
8. The method of claim 1, wherein the calcium sulfate hemihydrate is formed by immersing calcium sulfate dihydrate in a solution of water and an inorganic salt to form a mixture, and heating the mixture to substantially its boiling point at atmospheric pressure such that the calcium sulfate dihydrate is converted to calcium sulfate hemihydrate.
9. The method of claim 1, wherein the bone graft material has a working time of at least 5 minutes following mixing.
10. The method of claim 1, wherein the bone graft material further comprises an accelerant.
11. The method of claim 10, wherein the accelerant is selected from the group consisting of calcium sulfate dihydrate, calcium sulfate dihydrate coated with sucrose, potassium sulfate, and sodium sulfate.
12. The method of claim 1, wherein the bone graft material further comprises one or more additives selected from the group consisting of bone marrow aspirate, platelet concentrate, blood, antibiotics, chemotherapeutic agents, growth factors, and analgesics.
13. The method of claim 1, wherein the diluent to powder weight ratio is 0.19:1 to 0.31:1.
14. The method of claim 1, wherein the powder comprises between about 99.8 to 100 percent by weight calcium sulfate hemihydrate.
15. The method of claim 1, wherein the calcium sulfate hemihydrate consists of thick, stubby, rod-like crystals having a low water carrying capacity.
16. The method of claim 1, wherein the applying step comprises injecting the paste into a bone defect.
17. A method for preparing a bone graft material for treating bone defects comprising the step of mixing a powder comprising calcium sulfate hemihydrate with a diluent to produce a bone graft material in the form of a paste, wherein when undergoing dry-testing, the bone graft material has a compressive strength of approximately 88 MPa within 24 hours after said mixing step.
18. The method of claim 17, wherein the bone graft material has a compressive strength exceeding approximately 106 MPa within 24 hours after said mixing step.
19. The method of claim 17, wherein the diluent is water or a solution comprising an inorganic salt or a cationic surface active agent.
20. The method of claim 17, wherein the calcium sulfate hemihydrate is formed by immersing calcium sulfate dihydrate in a solution of water and an inorganic salt to form a mixture, and heating the mixture to substantially its boiling point at atmospheric pressure such that the calcium sulfate dihydrate is converted to calcium sulfate hemihydrate.
21-47. (canceled)
US16/125,199 2003-02-04 2018-09-07 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects Abandoned US20190135696A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US16/125,199 US20190135696A1 (en) 2003-02-04 2018-09-07 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US44469003P 2003-02-04 2003-02-04
US10/772,108 US7507257B2 (en) 2003-02-04 2004-02-04 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects
US12/372,328 US20090149553A1 (en) 2003-02-04 2009-02-17 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects
US16/125,199 US20190135696A1 (en) 2003-02-04 2018-09-07 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US12/372,328 Continuation US20090149553A1 (en) 2003-02-04 2009-02-17 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects

Publications (1)

Publication Number Publication Date
US20190135696A1 true US20190135696A1 (en) 2019-05-09

Family

ID=33313230

Family Applications (3)

Application Number Title Priority Date Filing Date
US10/772,108 Active 2026-05-20 US7507257B2 (en) 2003-02-04 2004-02-04 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects
US12/372,328 Abandoned US20090149553A1 (en) 2003-02-04 2009-02-17 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects
US16/125,199 Abandoned US20190135696A1 (en) 2003-02-04 2018-09-07 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US10/772,108 Active 2026-05-20 US7507257B2 (en) 2003-02-04 2004-02-04 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects
US12/372,328 Abandoned US20090149553A1 (en) 2003-02-04 2009-02-17 Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects

Country Status (1)

Country Link
US (3) US7507257B2 (en)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030228288A1 (en) * 1999-10-15 2003-12-11 Scarborough Nelson L. Volume maintaining osteoinductive/osteoconductive compositions
US9387094B2 (en) 2000-07-19 2016-07-12 Warsaw Orthopedic, Inc. Osteoimplant and method of making same
US7323193B2 (en) 2001-12-14 2008-01-29 Osteotech, Inc. Method of making demineralized bone particles
EP2295088B1 (en) 2001-10-12 2016-12-07 Warsaw Orthopedic, Inc. Improved bone graft
NZ544050A (en) 2003-06-11 2009-03-31 Osteotech Inc Osteoimplants and methods for their manufacture
CA2594733A1 (en) * 2005-01-14 2006-07-20 Osteotech, Inc. Expandable osteoimplant
US7754246B2 (en) 2005-09-09 2010-07-13 Wright Medical Technology, Inc. Composite bone graft substitute cement and articles produced therefrom
US8025903B2 (en) 2005-09-09 2011-09-27 Wright Medical Technology, Inc. Composite bone graft substitute cement and articles produced therefrom
WO2007056671A1 (en) * 2005-11-02 2007-05-18 Osteotech, Inc. Hemostatic bone graft
CN100569300C (en) * 2006-09-20 2009-12-16 叶南辉 Finished product capable of controlling dissolution rate of biomedical orthopedic implant material and manufacturing method
US7767226B2 (en) * 2007-01-30 2010-08-03 The Research Foundation Of State University Of New York Calcium sulfate based nanoparticles
EP2358352B1 (en) 2008-10-24 2018-08-29 Warsaw Orthopedic, Inc. Compositions and methods for promoting bone formation
TWI579007B (en) 2010-07-02 2017-04-21 艾格諾福斯保健公司 Use of bone regenerative material
TWI651103B (en) 2013-12-13 2019-02-21 萊特醫技股份有限公司 Multiphase bone graft replacement material
CN115400272B (en) * 2022-09-21 2023-07-11 松山湖材料实验室 Calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and preparation method thereof
CN115414525B (en) * 2022-09-26 2023-08-18 杭州归领医疗器械有限公司 Medical calcium sulfate artificial bone powder with core-shell structure and preparation method thereof

Family Cites Families (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US514403A (en) * 1894-02-06 James c
US1901051A (en) * 1929-08-08 1933-03-14 United States Gypsum Co High strength calcined gypsum and process of manufacturing same
US2616789A (en) 1951-03-19 1952-11-04 Certain Teed Prod Corp Method of producing gypsum plaster
US3573947A (en) 1968-08-19 1971-04-06 United States Gypsum Co Accelerator for gypsum plaster
US3813312A (en) 1970-10-05 1974-05-28 W Kinkade Process for making gypsum board
US3870538A (en) * 1973-05-07 1975-03-11 Nat Gypsum Co Gypsum set accelerator
US4430760A (en) 1981-12-18 1984-02-14 Collagen Corporation Nonstress-bearing implantable bone prosthesis
US4820306A (en) 1981-06-22 1989-04-11 Sterling Drug Inc. Method for augmentation of the alveolar ridge
US4619655A (en) 1984-01-26 1986-10-28 University Of North Carolina Plaster of Paris as a bioresorbable scaffold in implants for bone repair
US4596574A (en) 1984-05-14 1986-06-24 The Regents Of The University Of California Biodegradable porous ceramic delivery system for bone morphogenetic protein
CH671337A5 (en) 1984-06-19 1989-08-31 Ceskoslovenska Akademie Ved
US4595713A (en) 1985-01-22 1986-06-17 Hexcel Corporation Medical putty for tissue augmentation
US4650665A (en) 1985-02-08 1987-03-17 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
US4568536A (en) 1985-02-08 1986-02-04 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
GB8514055D0 (en) 1985-06-04 1985-07-10 Geistlich Soehne Ag Chemical substance
US4681763A (en) 1985-06-11 1987-07-21 University Of Medicine And Dentistry Of New Jersey Composition for stimulating bone growth
US4693986A (en) * 1985-06-25 1987-09-15 Orthomatrix, Inc. Ceramic process and products
US4778834A (en) * 1987-02-24 1988-10-18 Sterling Drug Inc. Hydroxylapatite-synthetic resin composites
US4892734A (en) 1987-04-06 1990-01-09 Endocon, Inc. Dispensing paste for forming medicinal pellets
GB2205089B (en) * 1987-05-22 1991-03-13 Rhein Westfael Elect Werk Ag Process for production of calcium sulphate alpha-hemihydrate
US4880660A (en) 1987-08-28 1989-11-14 Minnesota Mining And Manufacturing Company Method for priming hard tissue
US5162114A (en) 1989-02-23 1992-11-10 Stryker Corporation Bone collagen matrix for xenogenic implants
US4975526A (en) 1989-02-23 1990-12-04 Creative Biomolecules, Inc. Bone collagen matrix for zenogenic implants
US5047031A (en) * 1988-04-20 1991-09-10 Norian Corporation In situ calcium phosphate minerals method
US4880610A (en) * 1988-04-20 1989-11-14 Norian Corporation In situ calcium phosphate minerals--method and composition
GB8813033D0 (en) 1988-06-02 1988-07-06 Geistlich Soehne Ag Chemical compound
US4994030A (en) 1988-06-28 1991-02-19 Osteotech, Inc. Reconstitution of human bone and tissue
US5573771A (en) 1988-08-19 1996-11-12 Osteomedical Limited Medicinal bone mineral products
US5264214A (en) 1988-11-21 1993-11-23 Collagen Corporation Composition for bone repair
US5147403A (en) 1989-03-15 1992-09-15 United States Gypsum Company Prosthesis implantation method
US5487897A (en) 1989-07-24 1996-01-30 Atrix Laboratories, Inc. Biodegradable implant precursor
US5061286A (en) 1989-08-18 1991-10-29 Osteotech, Inc. Osteoprosthetic implant
US5073373A (en) 1989-09-21 1991-12-17 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US5290558A (en) 1989-09-21 1994-03-01 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US5236456A (en) 1989-11-09 1993-08-17 Osteotech, Inc. Osteogenic composition and implant containing same
US5425769A (en) * 1990-04-23 1995-06-20 Snyders, Jr.; Robert V. Composition of material for osseous repair
DE69111021T2 (en) 1990-10-31 1996-01-04 Gendler El Flexible membrane made from organic bone matrix for repairing and restoring bones.
US5462722A (en) 1991-04-17 1995-10-31 Liu; Sung-Tsuen Calcium phosphate calcium sulfate composite implant material
DE4121043A1 (en) 1991-06-26 1993-01-07 Merck Patent Gmbh BONE REPLACEMENT MATERIAL WITH FGF
US5356629A (en) 1991-07-12 1994-10-18 United States Surgical Corporation Composition for effecting bone repair
US5769897A (en) 1991-12-13 1998-06-23 Haerle; Anton Synthetic bone
US5314476A (en) 1992-02-04 1994-05-24 Osteotech, Inc. Demineralized bone particles and flowable osteogenic composition containing same
US5219897A (en) 1992-02-10 1993-06-15 Murray William M Dental and orthopedic cement method and preforms
US5236971A (en) 1992-02-10 1993-08-17 Murray William M Dental and orthopedic cement method and preforms
US5336699A (en) 1992-02-20 1994-08-09 Orthopaedic Research Institute Bone cement having chemically joined reinforcing fillers
US5366507A (en) 1992-03-06 1994-11-22 Sottosanti John S Method for use in bone tissue regeneration
US5320844A (en) 1992-03-12 1994-06-14 Liu Sung Tsuen Composite materials for hard tissue replacement
US5334626A (en) 1992-07-28 1994-08-02 Zimmer, Inc. Bone cement composition and method of manufacture
FR2705235B1 (en) 1993-05-13 1995-07-13 Inoteb Use of particles of a biocompatible and bioresorbable calcium salt as an active ingredient in the preparation of a medicament for the local treatment of demineralizing bone diseases.
US5531791A (en) 1993-07-23 1996-07-02 Bioscience Consultants Composition for repair of defects in osseous tissues, method of making, and prosthesis
US5385887A (en) 1993-09-10 1995-01-31 Genetics Institute, Inc. Formulations for delivery of osteogenic proteins
US5482551A (en) 1993-09-20 1996-01-09 Armstrong World Industries, Inc. Extruded fire resistant construction and building products
US5681873A (en) 1993-10-14 1997-10-28 Atrix Laboratories, Inc. Biodegradable polymeric composition
US5507813A (en) 1993-12-09 1996-04-16 Osteotech, Inc. Shaped materials derived from elongate bone particles
US5763416A (en) 1994-02-18 1998-06-09 The Regent Of The University Of Michigan Gene transfer into bone cells and tissues
US5626861A (en) * 1994-04-01 1997-05-06 Massachusetts Institute Of Technology Polymeric-hydroxyapatite bone composite
GB9407135D0 (en) 1994-04-11 1994-06-01 Aberdeen University And Plasma Treatment of osteoporosis
US6056670A (en) * 1994-05-25 2000-05-02 Unisen, Inc. Power controlled exercising machine and method for controlling the same
US5578662A (en) 1994-07-22 1996-11-26 United States Surgical Corporation Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom
US5496399A (en) * 1994-08-23 1996-03-05 Norian Corporation Storage stable calcium phosphate cements
US5707962A (en) 1994-09-28 1998-01-13 Gensci Regeneration Sciences Inc. Compositions with enhanced osteogenic potential, method for making the same and therapeutic uses thereof
TW369414B (en) 1994-09-30 1999-09-11 Yamanouchi Pharma Co Ltd Bone formation transplant
US5614206A (en) 1995-03-07 1997-03-25 Wright Medical Technology, Inc. Controlled dissolution pellet containing calcium sulfate
EP0851772A1 (en) 1995-06-06 1998-07-08 Gensci Regeneration Laboratories, Inc. Modified osteogenic materials
US5700289A (en) 1995-10-20 1997-12-23 North Shore University Hospital Research Corporation Tissue-engineered bone repair using cultured periosteal cells
US6048964A (en) 1995-12-12 2000-04-11 Stryker Corporation Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
US5788976A (en) 1996-02-12 1998-08-04 Wbk, Inc. Method for effecting bone repair
US5824078A (en) 1996-03-11 1998-10-20 The Board Of Trustees Of The University Of Arkansas Composite allograft, press, and methods
US6051247A (en) 1996-05-30 2000-04-18 University Of Florida Research Foundation, Inc. Moldable bioactive compositions
US5727945A (en) 1996-08-26 1998-03-17 Dannenbaum; Richard M. Impregnated barrier and method of assisting bone or tissue regeneration
US5676146B1 (en) 1996-09-13 2000-04-18 Osteotech Inc Surgical implant containing a resorbable radiopaque marker and method of locating such within a body
US5964805A (en) 1997-02-12 1999-10-12 Stone; Kevin R. Method and paste for articular cartilage transplantation
US6037519A (en) 1997-10-20 2000-03-14 Sdgi Holdings, Inc. Ceramic fusion implants and compositions
US5756127A (en) 1996-10-29 1998-05-26 Wright Medical Technology, Inc. Implantable bioresorbable string of calcium sulfate beads
US5866155A (en) * 1996-11-20 1999-02-02 Allegheny Health, Education And Research Foundation Methods for using microsphere polymers in bone replacement matrices and composition produced thereby
GB9626320D0 (en) * 1996-12-19 1997-02-05 Ecc Int Ltd Cementitious compositions
AU6019898A (en) 1997-01-09 1998-08-03 Cohesion Technologies, Inc. Devices for tissue repair and methods for preparation and use thereof
US20020098222A1 (en) 1997-03-13 2002-07-25 John F. Wironen Bone paste
US5948426A (en) 1997-05-03 1999-09-07 Jefferies; Steven R. Method and article to induce hematopoietic expansion
US5861445A (en) 1997-05-08 1999-01-19 American Dental Association Health Foundation Reinforcement of dental and other composite materials
US5972368A (en) 1997-06-11 1999-10-26 Sdgi Holdings, Inc. Bone graft composites and spacers
US5910315A (en) 1997-07-18 1999-06-08 Stevenson; Sharon Allograft tissue material for filling spinal fusion cages or related surgical spaces
US5899939A (en) 1998-01-21 1999-05-04 Osteotech, Inc. Bone-derived implant for load-supporting applications
US6030635A (en) 1998-02-27 2000-02-29 Musculoskeletal Transplant Foundation Malleable paste for filling bone defects
US6056970A (en) 1998-05-07 2000-05-02 Genzyme Corporation Compositions comprising hemostatic compounds and bioabsorbable polymers
US6224635B1 (en) 1998-11-06 2001-05-01 Hospital For Joint Diseases Implantation of surgical implants with calcium sulfate
DE60017363T2 (en) 1999-02-02 2006-03-02 Wright Medical Technology Inc., Arlington CONTROLLED RELEASE OF A COMPOSITE MATERIAL
US7371408B1 (en) 1999-06-07 2008-05-13 Wright Medical Technology, Inc. Bone graft substitute composition
US6340477B1 (en) 2000-04-27 2002-01-22 Lifenet Bone matrix composition and methods for making and using same
US6375935B1 (en) * 2000-04-28 2002-04-23 Brent R. Constantz Calcium phosphate cements prepared from silicate solutions
SE517168C2 (en) * 2000-07-17 2002-04-23 Bone Support Ab A composition for an injectable bone mineral replacement material
US6770695B2 (en) 2000-08-07 2004-08-03 John L. Ricci Time release calcium sulfate matrix for bone augmentation
US6652825B2 (en) * 2001-05-01 2003-11-25 National Gypsum Properties Llc Method of producing calcium sulfate alpha-hemihydrate
US7371409B2 (en) 2001-09-06 2008-05-13 Wright Medical Technology, Inc. Bone graft substitute composition
DE60335248D1 (en) 2002-03-29 2011-01-20 Wright Medical Tech Inc BONE GRAFT SUBSTITUTE COMPOSITION
US6652887B1 (en) 2002-06-24 2003-11-25 Wright Medical Technology, Inc. Bone graft substitute composition
US7291179B2 (en) 2002-06-24 2007-11-06 Wright Medical Technology, Inc. Bone graft substitute composition
US7250550B2 (en) * 2004-10-22 2007-07-31 Wright Medical Technology, Inc. Synthetic bone substitute material

Also Published As

Publication number Publication date
US20040220681A1 (en) 2004-11-04
US20090149553A1 (en) 2009-06-11
US7507257B2 (en) 2009-03-24

Similar Documents

Publication Publication Date Title
US20190135696A1 (en) Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects
US7658768B2 (en) Bone graft substitute composition
CN1229146C (en) Bone cement that is bioactive and treats osteoporosis
US8968465B2 (en) Bone graft substitute composition
US20070233213A1 (en) Method of therapeutic treatment using a biocompatible ceramic composition
WO2004000334A1 (en) Bone graft substitute composition
EP3166651B1 (en) Injectable bone substitutes for augmenting implant fixation
US9351812B2 (en) Calcium aluminate based paste for stabilizing dental implants and restoring tissue attachment after surgery and methods therefor
CN100531805C (en) Injectable self-cured calcium phosphate bone-rehabilitating material and its preparing process
EP3228334A1 (en) Phosphocalcic cement composition comprising blood
US12343444B2 (en) Structural implant to prevent bone defects
US20250319233A1 (en) Fiber-Reinforced Bio-Material Composition and Methods of Use
US20250049985A1 (en) Bone adhesive composition
EP4096730B1 (en) Improved bone graft substitute formulation
KR100435418B1 (en) Composition for stimulating bone-forming and bone-consolidation
WO2024133602A1 (en) Bioadhesive composition
JP2023528411A (en) Biomaterial compositions and methods of use thereof in craniomaxillofacial surgery
WO2017011448A1 (en) Bio-material composition and methods of use

Legal Events

Date Code Title Description
STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

AS Assignment

Owner name: WRIGHT MEDICAL TECHNOLOGY, INC., TENNESSEE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:COLE, JANTZEN A.;CARROLL, MICHAEL E.;MOSELEY, JON P.;AND OTHERS;SIGNING DATES FROM 20040524 TO 20040607;REEL/FRAME:049644/0828

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: FINAL REJECTION MAILED

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION