WO2008073628A2 - Compositions and methods for arthrodetic procedures - Google Patents

Compositions and methods for arthrodetic procedures Download PDF

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Publication number
WO2008073628A2
WO2008073628A2 PCT/US2007/083638 US2007083638W WO2008073628A2 WO 2008073628 A2 WO2008073628 A2 WO 2008073628A2 US 2007083638 W US2007083638 W US 2007083638W WO 2008073628 A2 WO2008073628 A2 WO 2008073628A2
Authority
WO
WIPO (PCT)
Prior art keywords
pdgf
biocompatible matrix
bone
biocompatible
solution
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.)
Ceased
Application number
PCT/US2007/083638
Other languages
English (en)
French (fr)
Other versions
WO2008073628A3 (en
Inventor
Charles E. Hart
Samuel E. Lynch
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.)
Biomimetic Therapeutics LLC
Original Assignee
Biomimetic Therapeutics LLC
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
Priority to CA2668189A priority Critical patent/CA2668189C/en
Priority to AU2007333425A priority patent/AU2007333425B2/en
Priority to US12/513,491 priority patent/US8106008B2/en
Priority to JP2009535493A priority patent/JP5552315B2/ja
Priority to HK10101413.5A priority patent/HK1137670B/en
Priority to EP07871368.2A priority patent/EP2086598B1/en
Application filed by Biomimetic Therapeutics LLC filed Critical Biomimetic Therapeutics LLC
Priority to EP16196737.7A priority patent/EP3181157B1/en
Publication of WO2008073628A2 publication Critical patent/WO2008073628A2/en
Anticipated expiration legal-status Critical
Publication of WO2008073628A3 publication Critical patent/WO2008073628A3/en
Priority to US13/349,413 priority patent/US8399409B2/en
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61F2002/2817—Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • 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
    • A61F2002/30621—Features concerning the anatomical functioning or articulation of the prosthetic joint
    • A61F2002/30622—Implant for fusing a joint or bone 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
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005—The prosthesis being constructed from a particular material
    • A61F2310/00179—Ceramics or ceramic-like structures
    • A61F2310/00293—Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • 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

Definitions

  • the present invention relates to compositions and methods useful for arthrodetic procedures and for promoting fusion of bones in a joint.
  • arthrodetic procedures are used to treat musculoskeletal problems associated with various joints of patients.
  • Arthrodetic procedures and arthrodesis refer to the surgical immobilization of a joint resulting from fusion of bones of the joint.
  • Arthrodesis of the foot and ankle is a commonly utilized procedure for the treatment of multiple etiologies of foot and ankle pathology, including post-traumatic arthritis, inflammatory arthropathy, seronegative arthropathy, significant joint instability, suboptimal alignment and/or pain.
  • PDGF is present in the solution in a concentration ranging from about 0.01 mg/ml to about 10 mg/ml, from about 0.05 mg/ml to about 5 mg/ml, from about 0.1 mg/ml to about 1.0 mg/ml or from about 0.2 mg/ml to about 0.4 mg/ml.
  • concentration of PDGF within the solution may be within any of the concentration ranges stated above.
  • PDGF comprises PDGF homodimers and heterodimers, including PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, PDGF-DD, and mixtures and derivatives thereof.
  • PDGF comprises PDGF-BB.
  • PDGF comprises a recombinant human (rh) PDGF such as rhPDGF-BB.
  • Exemplary bone substituting agents include, e.g., a calcium phosphate (e.g., tricalcium phosphate (e.g., ⁇ -TCP), hydroxyapatite, poorly crystalline hydroxyapatite, amorphous calcium phosphate, calcium metaphosphate, dicalcium phosphate dihydrate, heptacalcium phosphate, calcium pyrophosphate dihydrate, calcium pyrophosphate, and octacalcium phosphate), calcium sulfate, or demineralized bone (e.g., demineralized freeze-dried cortical or cancellous bone)).
  • the PDGF solution may have any concentration of PDGF as described herein.
  • the present invention provides a kit for use in arthrodetic procedures comprising a biocompatible matrix in a first package and a solution comprising PDGF in a second package.
  • the solution comprises a predetermined concentration of PDGF.
  • concentration of the PDGF can be predetermined according to requirements of the arthrodetic procedure(s) being performed.
  • the biocompatible matrix can be present in the kit in a predetermined amount.
  • the biocompatible matrix in the kit comprises a bone scaffolding material, a bone scaffolding material and a biocompatible binder, and/or bone allograft such as DFDBA or particulate DBM.
  • an arthrodetic procedure comprises subtalar arthrodesis. In other embodiments, an arthrodetic procedure comprises talonavicular arthrodesis. In another embodiment, an arthrodetic procedure comprises triple arthrodesis. In some embodiments, an arthrodetic procedure comprises a calcaneocuboid arthrodesis. In a further embodiment, an arthrodetic procedure comprises an ankle arthrodesis.
  • compositions of the present invention comprise a solution comprising PDGF.
  • PDGF can be partially purified.
  • Partially purified PDGF comprises compositions having PDGF in the context of platelet rich plasma (PRP), fresh frozen plasma (FFP), or any other blood product that requires collection and separation to produce PDGF.
  • PRP platelet rich plasma
  • FFP fresh frozen plasma
  • Embodiments of the present invention contemplate that any of the PDGF isoforms provided herein, including homodimers and heterodimers, can be purified or partially purified.
  • Compositions of the present invention containing PDGF mixtures may contain PDGF isoforms or PDGF fragments in partially purified proportions.
  • Partially purified and purified PDGF in some embodiments, can be prepared as described in U.S. Patent Application Serial No. 11/159,533 (Publication No: 20060084602).
  • the PDGF solution preferably has a pH from about 3.0 to about 7.0 or from about 4.0 to about 6.0.
  • the biological activity of PDGF can be optimized in a solution having a neutral pH range. Therefore, in a further embodiment, the present invention comprises a neutral pH formulation of a PDGF solution.
  • the PDGF solution has a pH from about 5.0 to about 8.0, from about 5.5 to about 7.0, or from about 5.5 to about 6.5.
  • an acidic PDGF solution is reformulated to a neutral pH composition, wherein such composition is then used to fuse bones in a joint.
  • the PDGF utilized in the solutions is rh-PDGF- BB.
  • the pH of the PDGF containing solution can be altered to optimize the binding kinetics of PDGF to a biocompatible matrix.
  • a biocompatible matrix comprises a bone scaffolding material. It is to be understood that the terms bone scaffolding material and bone substituting agent are used interchangeably in this patent application.
  • the bone scaffolding material provides the framework or scaffold for new bone and tissue growth to occur.
  • a bone substituting agent is one that can be used to permanently or temporarily replace bone. Following implantation, the bone substituting agent can be retained by the body or it can be resorbed by the body and replaced with bone.
  • a bone scaffolding material comprises a plurality of particles.
  • a bone scaffolding material for example, can comprise a plurality of calcium phosphate particles.
  • Particles of a bone scaffolding material in some embodiments, can individually demonstrate any of the pore diameters and porosities provided herein for the bone scaffolding.
  • particles of a bone scaffolding material can form an association to produce a matrix having any of the pore diameters or porosities provided herein for the bone scaffolding material.
  • Bone scaffolding particles may be mm, ⁇ m or submicron (nm) in size. Bone scaffolding particles, in one embodiment, have an average diameter ranging from about 1 ⁇ m to about 5 mm.
  • a biocompatible matrix comprising a bone scaffolding material and a biocompatible binder can be flowable, moldable, and/or extrudable.
  • a biocompatible matrix can be in the form of a paste or putty.
  • a biocompatible matrix in the form of a paste or putty in one embodiment, can comprise particles of a bone scaffolding material adhered to one another by a biocompatible binder.
  • a collagen binder in some embodiments, can comprise any type of collagen, including Type I, Type II, and Type III collagens.
  • a collagen binder comprises a mixture of collagens, such as a mixture of Type I and Type II collagen.
  • a collagen binder is soluble under physiological conditions.
  • Other types of collagen present in bone or musculoskeletal tissues may be employed. Recombinant, synthetic and naturally occurring forms of collagen may be used in the present invention.
  • a biocompatible matrix can comprise a plurality of ⁇ -
  • a biocompatible matrix comprising ⁇ -TCP particles and a collagen binder can comprise pores having diameters ranging from about 1 ⁇ m to about 1 mm.
  • a biocompatible matrix comprising ⁇ -TCP particles and a collagen binder can comprise macropores having diameters ranging from about 100 ⁇ m to about 1 mm, mesopores having diameters ranging from about 10 ⁇ m to 100 ⁇ m, and micropores having diameters less than about 10 ⁇ m.
  • a biocompatible matrix comprising ⁇ -TCP particles and a collagen binder can have a porosity greater than about 25% or greater than 40%.
  • the biocompatible matrix can have a porosity greater than about 50%, greater than about 60%, greater than about
  • a biocompatible matrix in paste or putty form comprising ⁇ -TCP particles and a collagen binder can retain a flowable and moldable form when implanted.
  • the paste or putty can harden subsequent to implantation, thereby reducing matrix flowability and moldability.
  • Non-limiting examples of biologically active compounds that can be incorporated into compositions of the present invention including, e.g., anti-cancer agents, antibiotics, analgesics, anti-inflammatory agents, immunosuppressants, enzyme inhibitors, antihistamines, hormones, muscle relaxants, prostaglandins, trophic factors, osteoinductive proteins, growth factors, and vaccines, are disclosed in U.S. Patent Application Serial No. 11/159,533 (Publication No: 20060084602).
  • biologically active compounds that can be incorporated into compositions of the present invention include osteoinductive factors such as insulin-like growth factors, fibroblast growth factors, or other PDGFs.
  • a composition for promoting bone fusion in arthrodetic procedures can further comprise the addition of other bone grafting materials with PDGF including autologous bone marrow, autologous platelet extracts, and synthetic bone matrix materials.
  • arthrodetic procedures comprise arthrodesis of the foot and ankle including subtalar arthrodesis, talonavicular arthrodesis, triple arthrodesis, and ankle arthrodesis.
  • Example 3 describes a study designed to demonstrate the efficacy of compositions and methods of the present invention for promoting bone fusion in arthrodetic procedures of the foot and ankle.
  • a ratio of about 3 ml of rhPDGF-BB solution to about 1 g dry weight of the ⁇ -TCP biocompatible matrix was used to produce the composition.
  • the rhPDGF-BB solution was expelled on the ⁇ -TCP particles of the biocompatible matrix with a syringe, and the resulting composition was blended and molded in preparation for application at a site of bone fusion in a joint.
  • a composition of the present invention comprising a PDGF solution disposed in a ⁇ -TCP matrix was prepared or ABG was harvested, locally or from the iliac crest, based upon the randomization schedule. Subjects consented to harvesting of local or iliac crest bone graft prior to the surgical procedure, as the subject was blinded to the randomization assignment. For subjects randomized to receive ABG, the harvest site and amount of bone graft was documented on the case report form. Autograft was harvested according to standard bone grafting procedures. The graft material ( ⁇ -TCP-PDGF or ABG) was packed into the fusion site at the time of fixation such that the graft material was in contact with the entire surface area of the joint to be fused.
  • compositions comprising a solution comprising 0.3 mg/ml PDGF disposed in a ⁇ -TCP matrix with or without a collagen binder compared to autologous bone graft in partial arthrodesis of the carpus in dogs.
  • the clinical significance of comparing a composition of the present invention to autograft provides for a predictable synthetic alternative to autograft, thus eliminating the morbidity and increased surgical time associated with an additional procedure for harvesting autogenous bone graft which is only available in limited quantities.
  • Standard anteroposterior (AP) x-rays were taken at weekly intervals of each animal to assess fixation and to assess new bone formation and fusion of bones bridging the treated joints.
  • Specimen limbs from each group were immersed in 10% formalin for one week, rinsed in water for 24 hours, and subsequently immersed in 70% ethanol. Dehydration was accomplished with an ascending series of alcohols starting from 80% and progressing serially to 90%, 95%, and 100%. Alcohol was cleared with 100% acetone. Each specimen was embedded in Spurrs plastic for calcified histology.
  • joints treated with compositions comprising rhPDGF-BB displayed enhanced osseous bridging and fusion.
  • ⁇ -TCP compositions comprising rhPDGF-BB demonstrated osseous bridging and joint fusion results comparable to autograft compositions, thereby precluding the necessity to harvest autograft for arthrodetic procedures. Eliminating autograft harvesting from arthrodetic procedures reduces patient pain and discomfort while facilitating the joint fusion process.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
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  • Materials For Medical Uses (AREA)
PCT/US2007/083638 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures Ceased WO2008073628A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU2007333425A AU2007333425B2 (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures
US12/513,491 US8106008B2 (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures
JP2009535493A JP5552315B2 (ja) 2006-11-03 2007-11-05 アースロデティック術のための組成物および方法
HK10101413.5A HK1137670B (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures
EP07871368.2A EP2086598B1 (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures
CA2668189A CA2668189C (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures comprising a solution of platelet derived growth factor (pdgf) incorporated in a biocompatible matrix
EP16196737.7A EP3181157B1 (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures
US13/349,413 US8399409B2 (en) 2006-11-03 2012-01-12 Compositions and methods for arthrodetic procedures

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US85658806P 2006-11-03 2006-11-03
US60/856,588 2006-11-03

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/513,491 A-371-Of-International US8106008B2 (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures
US13/349,413 Continuation US8399409B2 (en) 2006-11-03 2012-01-12 Compositions and methods for arthrodetic procedures

Publications (2)

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WO2008073628A2 true WO2008073628A2 (en) 2008-06-19
WO2008073628A3 WO2008073628A3 (en) 2009-07-02

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PCT/US2007/083638 Ceased WO2008073628A2 (en) 2006-11-03 2007-11-05 Compositions and methods for arthrodetic procedures

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US (2) US8106008B2 (cg-RX-API-DMAC7.html)
EP (3) EP2086598B1 (cg-RX-API-DMAC7.html)
JP (4) JP5552315B2 (cg-RX-API-DMAC7.html)
AU (1) AU2007333425B2 (cg-RX-API-DMAC7.html)
CA (1) CA2668189C (cg-RX-API-DMAC7.html)
WO (1) WO2008073628A2 (cg-RX-API-DMAC7.html)

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US20100129415A1 (en) * 2008-11-25 2010-05-27 Warsaw Orthopedic, Inc. Bone regeneration device
WO2010102266A1 (en) * 2009-03-05 2010-09-10 Biomimetic Therapeutics, Inc. Platelet-derived growth factor compositions and methods for the treatment of osteochondral defects
US7943573B2 (en) 2008-02-07 2011-05-17 Biomimetic Therapeutics, Inc. Methods for treatment of distraction osteogenesis using PDGF
US8106008B2 (en) 2006-11-03 2012-01-31 Biomimetic Therapeutics, Inc. Compositions and methods for arthrodetic procedures
US8114841B2 (en) 2004-10-14 2012-02-14 Biomimetic Therapeutics, Inc. Maxillofacial bone augmentation using rhPDGF-BB and a biocompatible matrix
CN103491888A (zh) * 2010-12-13 2014-01-01 生物模拟治疗有限责任公司 用于脊柱融合手术的组合物和方法
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
US9545377B2 (en) 2004-10-14 2017-01-17 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods of use thereof
US9642891B2 (en) 2006-06-30 2017-05-09 Biomimetic Therapeutics, Llc Compositions and methods for treating rotator cuff injuries
US10071182B2 (en) 2014-10-14 2018-09-11 Samuel E. Lynch Methods for treating wounds
US10258566B2 (en) 2004-10-14 2019-04-16 Biomimetic Therapeutics, Llc Compositions and methods for treating bone
US10531957B2 (en) 2015-05-21 2020-01-14 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
EP3938000A4 (en) * 2019-03-14 2022-11-16 BioMimetic Therapeutics, LLC PLATELET DERIVED GROWTH FACTOR FORMULATIONS TO IMPROVE BONE FUSION

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CA2623106C (en) * 2005-09-19 2013-12-24 Histogenics Corporation Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof
US20100151025A1 (en) * 2007-02-20 2010-06-17 Biomimetic Therapeutics, Inc. Prevention and treatment for osteonecrosis and osteoradionecrosis of the jaw
CN110075069A (zh) * 2009-05-06 2019-08-02 实验室护肤股份有限公司 包含活性剂-磷酸钙颗粒复合物的皮肤递送组合物及其应用
EP2622062A4 (en) * 2010-10-01 2014-05-14 Univ Columbia PDGF-INDUCED CELL HOMING
AU2012207203B2 (en) 2011-01-19 2017-08-03 Laboratory Skin Care, Inc. Topical minocycline compositions and methods of using the same
US9248164B2 (en) 2011-05-13 2016-02-02 School Juridical Person Kitasato Institute Growth factor anchoring type bone graft material, method for producing growth factor anchoring type bone graft material, kit for producing growth factor anchoring type bone graft material, and method for forming bone
US10207027B2 (en) 2012-06-11 2019-02-19 Globus Medical, Inc. Bioactive bone graft substitutes
JP2016514696A (ja) 2013-03-15 2016-05-23 ラボラトリー スキン ケア インコーポレイテッド 微細乾燥粒子状レスベラトロール活性剤組成物およびそれを含む局所製剤
US9486483B2 (en) 2013-10-18 2016-11-08 Globus Medical, Inc. Bone grafts including osteogenic stem cells, and methods relating to the same
US9539286B2 (en) 2013-10-18 2017-01-10 Globus Medical, Inc. Bone grafts including osteogenic stem cells, and methods relating to the same
US9579421B2 (en) 2014-02-07 2017-02-28 Globus Medical Inc. Bone grafts and methods of making and using bone grafts
US9463264B2 (en) 2014-02-11 2016-10-11 Globus Medical, Inc. Bone grafts and methods of making and using bone grafts
US10016529B2 (en) 2015-06-10 2018-07-10 Globus Medical, Inc. Biomaterial compositions, implants, and methods of making the same
US11426489B2 (en) 2015-06-10 2022-08-30 Globus Medical, Inc. Biomaterial compositions, implants, and methods of making the same
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