WO2018144496A1 - Methods and compositions for matrix preparation - Google Patents

Methods and compositions for matrix preparation Download PDF

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Publication number
WO2018144496A1
WO2018144496A1 PCT/US2018/016069 US2018016069W WO2018144496A1 WO 2018144496 A1 WO2018144496 A1 WO 2018144496A1 US 2018016069 W US2018016069 W US 2018016069W WO 2018144496 A1 WO2018144496 A1 WO 2018144496A1
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Prior art keywords
collagen
matrix
clauses
buffer solution
kit
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PCT/US2018/016069
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English (en)
French (fr)
Inventor
Sherry L. Voytik-Harbin
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Geniphys Inc
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Geniphys Inc
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Priority to CA3052266A priority Critical patent/CA3052266A1/en
Priority to EP18747153.7A priority patent/EP3576775B1/en
Priority to ES18747153T priority patent/ES3040675T3/es
Priority to JP2019562223A priority patent/JP7242553B2/ja
Priority to CN201880019401.8A priority patent/CN110446500B/zh
Priority to US16/482,465 priority patent/US12280176B2/en
Publication of WO2018144496A1 publication Critical patent/WO2018144496A1/en
Anticipated expiration legal-status Critical
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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3633—Extracellular matrix [ECM]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
    • 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
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0029—Radiation
    • A61L2/0047—Ultraviolet radiation
    • 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
    • A61L27/24—Collagen
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • This invention relates to methods of preparing matrices, and compositions therefor.
  • the invention relates to methods of preparing collagen matrices, and compositions therefor, including kits and graft compositions.
  • Extracellular matrix plays a crucial role in the function of tissues and organs, such as communication between cells, differentiation during embryogenesis, wound healing, adhesion, and cell migration and proliferation.
  • Extracellular matrix graft constructs obtained from natural sources or made synthetically can be used as tissue graft compositions, in both solid and injectable forms, for remodeling tissues in vivo or for in vitro applications, such as for research purposes.
  • the principal component of the extracellular matrix is collagen.
  • Some solubilized collagen compositions, including purified collagen compositions have matrix- forming capability and can also be used as tissue graft compositions, in both solid and injectable forms, for remodeling tissues in vivo or for in vitro uses.
  • collagen-based matrices have broad spanning research and medical applications, including wound and hemostatic dressings, use as surgical implants, substrates for tissue engineered medical products, delivery vehicles for therapeutic cells or molecules, and as three-dimensional in-vitro tissue systems for basic research, including drug development and toxicity testing.
  • the inventors have developed a robust method with a single mixing step for polymerization of collagen, with reagents that mimic physiologic conditions to support supramolecular self-assembly of collagen as observed in the body.
  • the method and the reagents used in the method described herein are based on physiologic responses such as the viscoelastic properties of self-assembled matrices (for example, shear storage modulus as measured in oscillatory shear and matrix stiffness) as a function of collagen concentration in the polymerization reaction.
  • the methods and compositions described herein produce collagen- based matrices that have properties similar to conventional multi-step polymerization methods involving multiple mixing steps for collagen polymerization including mixing a collagen composition with a buffer solution and then mixing with, for example, with a base such as NaOH to induce polymerization, and then mixing optionally with other reagents.
  • the methods and compositions developed by the inventors have resulted in highly predictable and reproducible in-vitro cell and in-vivo host responses to self-assembled collagen matrices.
  • the inventors have developed methods for sterilizing the collagen, collagen compositions, collagen matrices, collagen solutions, and lyophilized collagen described herein by using ultraviolet radiation, while maintaining polymerization capabilities (e.g., shear storage modulus).
  • the maintenance of polymerization capabilities is contrary to previous studies reporting that ultraviolet radiation negatively affects collagen fibril formation (Mentor et al., Photodermatology, Photoimmunology & Photomedicine, 2001; Miyata et al., Biochem
  • a method for preparing a matrix comprises polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix.
  • a method for preparing a matrix comprises polymerizing collagen by mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix wherein the buffer solution does not contain magnesium ions or manganese ions.
  • a method for preparing a matrix comprises polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, wherein the collagen in the collagen solution polymerizes to form the matrix.
  • a collagen matrix prepared according to any of the preceding methods is provided.
  • a kit comprising a collagen composition and a buffer solution is provided.
  • a kit comprising lyophilized collagen, a hydrochloric acid solution, and a buffer solution is provided.
  • a method for preparing a matrix comprising polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix.
  • composition further comprises an acid.
  • the collagen matrix of clause 35 wherein the medical graft has a use selected from the group consisting of a tissue graft material, an injectable graft material, a wound dressing, a hemostatic dressing, a delivery vehicle for therapeutic cells, and a delivery vehicle for a therapeutic agent.
  • a kit comprising a collagen composition and a buffer solution.
  • kit of any one of clauses 39 to 59 further comprising instructions for use of components of the kit.
  • a method for preparing a matrix comprising polymerizing collagen by mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix wherein the buffer solution does not contain magnesium ions or manganese ions.
  • a collagen matrix prepared according to the method of any one of clauses 61 to 89.
  • the collagen matrix of clause 91 wherein the medical graft has a use selected from the group consisting of a tissue graft material, an injectable graft material, a wound dressing, a hemostatic dressing, a delivery vehicle for therapeutic cells, and a delivery vehicle for a therapeutic agent.
  • a kit comprising lyophilized collagen, a hydrochloric acid solution, and a buffer solution.
  • kit of any one of clauses 95 to 109 further comprising instructions for use of components of the kit.
  • a method for preparing a matrix comprising polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, wherein the collagen in the collagen solution polymerizes to form the matrix.
  • Fig. 1 shows shear storage modulus for collagen-based matrices polymerized at different oligomer concentrations.
  • the polymerization capacity for a single-step assembly is similar to that obtained with a conventional multi-step procedure.
  • Fig, 2 shows that self-assembled matrices prepared with a multi-step and single- step procedures show similar biocompatibility and cellular response.
  • Human adipose-derived stem cells were used to create three-dimensional collagen-fibril tissue constructs using a multi- step (fig. 2a) or single-step (fig. 2b) procedures. After 4 days, constructs were fixed, stained with phalloidin, and visualized using confocal microscopy.
  • Fig. 3 shows a multi-step procedure.
  • Fig. 4 shows a single-step procedure.
  • Fig. 5 shows the formulary supporting user customization of self-assembled collagen matrices using a single- step procedure based on starting collagen oligomer
  • FIG. 6 shows that research-grade and medical-grade formulations of oligomer show similar non-inflammatory tissue regeneration responses following subcutaneous injection in mice.
  • Research-grade oligomer, medical-grade oligomer, and Integra Flowable were subcutaneously injected (200 ul) in mice. After 4 weeks, implant sites were harvested, fixed, and prepared for histopathological analysis. Images show cross-sections of untreated skin (control; A), Integra Flowable (B), research-grade oligomer (C), and medical-grade oligomer (D).
  • Fig. 7 shows the shear storage modulus of collagen matrices polymerized from collagen treated with UVC irradiation at doses of 0 (untreated control), 30 mJ/cm 2 (1 minute of irradiation), and 300 mJ/cm 2 (10 minutes of irradiation).
  • contaminants means removing contaminants including, but not limited to, infectious agents.
  • contaminants e.g., viruses
  • infectious agents can be removed by inactivation, reduction in number or amount, or by inhibition of activity of contaminating agents, whether infectious or not.
  • purified means removing contaminants including, but not limited to, cellular contaminants, nucleotide contaminants, and endotoxins,
  • oligomer or “oligomers” in relation to collagen means collagen monomers (otherwise known as telocollagen) covalently attached to each other (e.g., collagen monomers attached to each other to form dimers, trimers, etc.).
  • a method for preparing a matrix comprises polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix.
  • a method for preparing a matrix comprises polymerizing collagen by mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix wherein the buffer solution does not contain magnesium ions or manganese ions.
  • a method for preparing a matrix comprises polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, wherein the collagen in the collagen solution polymerizes to form the matrix.
  • a collagen matrix prepared according to any of the preceding methods is provided.
  • a kit comprising a collagen composition and a buffer solution is provided.
  • a kit comprising lyophilized collagen, a hydrochloric acid solution, and a buffer solution is provided.
  • a method for preparing a matrix comprising polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix.
  • composition further comprises an acid.
  • the buffer solution further comprises about 0.1 mM to about 4 mM KC1.
  • the collagen matrix of clause 35 wherein the medical graft has a use selected from the group consisting of a tissue graft material, an injectable graft material, a wound dressing, a hemostatic dressing, a delivery vehicle for therapeutic cells, and a delivery vehicle for a therapeutic agent.
  • a kit comprising a collagen composition and a buffer solution.
  • the kit of clause 39 wherein the buffer solution comprises about .002 mM to about .02 mM MgCl 2 . 42. The kit of clause 39 wherein the buffer solution comprises less than about .02 mM MgCl 2 .
  • a method for preparing a matrix comprising polymerizing collagen by mixing a collagen composition with a buffer solution to form a collagen solution, and polymerizing the collagen in the collagen solution to form the matrix wherein the buffer solution does not contain magnesium ions or manganese ions.
  • a collagen matrix prepared according to the method of any one of clauses 61 to 89.
  • the collagen matrix of clause 90 wherein the collagen matrix is a medical graft.
  • the collagen matrix of clause 91 wherein the medical graft has a use selected from the group consisting of a tissue graft material, an injectable graft material, a wound dressing, a hemostatic dressing, a delivery vehicle for therapeutic cells, and a delivery vehicle for a therapeutic agent.
  • a kit comprising lyophilized collagen, a hydrochloric acid solution, and a buffer solution.
  • kit of any one of clauses 95 to 109 further comprising instructions for use of components of the kit.
  • a method for preparing a matrix comprising polymerizing collagen using a single mixing step comprising mixing a collagen composition with a buffer solution to form a collagen solution, wherein the collagen in the collagen solution polymerizes to form the matrix.
  • the collagen composition, the collagen solution, and/or the collagen matrix is sterilized using UVC irradiation.
  • the collagen can be prepared by methods described in Bailey JL, Critser PJ, Whittington C, Kuske JL, Yoder MC, Voytik-Harbin SL; Collagen oligomers modulate physical and biological properties of three- dimensional self-assembled matrices, Biopolymers (2011) 95(2):77-93, Kreger ST, Bell BJ, Bailey J, Stites E, Kuske J, Waisner B, Voytik-Harbin SL; Polymerization and matrix physical properties as important design considerations for soluble collagen formulations, Biopolymers (2010) 93(8):690-707, U.S. Patent Application Publication Number 20080268052, or U.S. Patent Application Publication Number 20120027732, each of which is incorporated herein by reference.
  • the collagen for use in the methods and compositions described herein can be obtained from any suitable source of collagen known in the art.
  • Exemplary collagen sources include submucosa tissues (U.S. Patents Nos. 4,902,508, 5,281,422, and 5,275,826), pericardial tissue, urinary bladder submucosa tissue, stomach submucosa tissue, liver basement membrane tissue, placental tissue, ovarian tissue, animal tail tissue, skin tissue (e.g., Gallop, et al., Preparation and Properties of Soluble Collagens, Meth. Enzymol. 6: 635-641 (1963), incorporated herein by reference), and extracellular matrix tissues generally.
  • compositions described herein can be any suitable type of collagen, including, but not limited to, Type I collagen, Type II collagen, Type III collagen, or Type IV collagen, or combinations thereof.
  • a tissue enriched in collagen oligomers e.g., pig skin tissue
  • the collagen can also be used to obtain the collagen for use in the methods and compositions described herein, or the collagen can be obtained from cells producing collagen oligomers (e.g., cells altered by recombinant techniques to express collagen oligomers), or by chemically
  • the collagen for use in the methods and compositions described herein can comprise oligomers or can consist of oligomers.
  • the collagen can comprise oligomers, and other forms of collagen such as monomers, telocollagen, and/or atelocollagen.
  • the collagen can be soluble collagen or solubilized collagen.
  • the collagen is substantially free of insoluble collagen, but may contain some insoluble collagen.
  • the collagen consists of soluble collagen or solubilized collagen.
  • the collagen, the collagen composition, the collagen matrix, the collagen solution, the lyophilized collagen, and/or the buffer solution can be sterilized using sterilization techniques known in the art, including but not limited to, propylene oxide or ethylene oxide treatment, gas plasma sterilization, gamma radiation (e.g., 1- 4 mrads), ultraviolet radiation (e.g., UVC irradiation), electron beam, viral filtration, sterile filtration (e.g., with a 0.22 ⁇ filter), chloroform exposure, and/or peracetic acid sterilization, and combinations thereof.
  • sterilization techniques known in the art, including but not limited to, propylene oxide or ethylene oxide treatment, gas plasma sterilization, gamma radiation (e.g., 1- 4 mrads), ultraviolet radiation (e.g., UVC irradiation), electron beam, viral filtration, sterile filtration (e.g., with a 0.22 ⁇ filter), chloroform exposure, and/or peracetic acid sterilization, and combinations thereof.
  • the sterilization procedure should not adversely affect the structure of collagen, the polymerization properties of the collagen, or the biological properties of the collagen that is sterilized.
  • the collagen can be sterilized before or after lyophilization (lyophilization procedures are described below).
  • the collagen matrix that results from collagen polymerization can maintain a polymerization property relative to collagen that is not irradiated, a collagen composition this is not irradiated, a collagen matrix that is not irradiated, a collagen solution that is not irradiated, or lyophilized collagen that is not irradiated, respectively.
  • the polymerization property can be selected from shear storage modulus, elastic modulus (Young's modulus), tensile modulus, compressive modulus, fibril architecture, proteolytic degradation, cellular signaling, and combinations thereof.
  • the ultraviolet radiation dose (e.g., UVC irradiation) can range from about 5 mJ/cm 2 to about 800 mJ/cm 2 , about 5 mJ/cm 2 to about 700 mJ/cm 2 , about 5 mJ/cm 2 to about 600 mJ/cm 2 , about 5 mJ/cm 2 to about 500 mJ/cm 2 , about 5
  • the sterilization inactivates viruses.
  • "inactivates viruses” means inactivating all viruses, whether infectious or not, reducing the number of infectious viruses, or inhibiting the activity of viruses, whether infectious or not.
  • the collagen for use in the methods and compositions described herein can be purified by methods known in the art for purifying collagen.
  • purified means removing contaminants including, but not limited to, cellular contaminants, nucleotide contaminants, and endotoxins.
  • the collagen can be purified by removing contaminants so that it is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% pure.
  • the collagen can be isolated.
  • isolated means substantially free of contaminants including, but not limited to, cellular contaminants, nucleotide contaminants, and endotoxins.
  • the collagen for use in the methods and compositions described herein can be lyophilized and then reconstituted to form the collagen composition for mixing with the buffer solution as described herein.
  • the reconstitution of the lyophilized collagen is not a mixing step for polymerization of the collagen.
  • lyophilized means that water is removed from the protein, compound, or composition, by, for example, freeze-drying under a vacuum. Any lyophilization method known to the skilled artisan can be used.
  • the collagen can be lyophilized in an acid, for example, acetic acid, hydrochloric acid, formic acid, lactic acid, citric acid, sulfuric acid, or phosphoric acid.
  • the collagen can be lyophilized in water.
  • cryoprotectants or lyoprotectants, or combinations thereof can be used during the lyophilization.
  • the lyophilized collagen can be reconstituted to form the collagen composition described herein for mixing with the buffer solution to polymerize the collagen.
  • the collagen can be reconstituted in an acidic solution or in water.
  • the acidic solution can comprise acetic acid, hydrochloric acid, formic acid, lactic acid, citric acid, sulfuric acid, or phosphoric acid.
  • the acidic solution for reconstitution can have a concentration of the acid of from about .005 N to about 0.1 N, from about .005 N to about .08 N, from about .005 N to about .06 N, from about .005 N to about 0.04 N, from about .005 N to about .02 N, from about .005 N to about .01 N, or about .01 N.
  • the acid can be hydrochloric acid and the hydrochloric acid can be about .005 N to about 0.1 N hydrochloric acid.
  • the acid can be hydrochloric acid and the hydrochloric acid can be about .01 N hydrochloric acid.
  • the collagen concentration in the collagen composition or in the collagen solution can be from about 0.1 mg/ml to about 40 mg/ml, from about 0.1 mg/ml to about 5 mg/ml, or from about 0.5 mg/ml to about 4 mg/ml.
  • the collagen concentration in the collagen composition or in the collagen solution can be from about 0.05 to about 5.0 mg/ml, about 1.0 mg/ml to about 3.0 mg/ml, about 0.05 mg/ml to about 10 mg/ml, about 0.05 to about 20 mg/ml, about 0.05 to about 30 mg/ml, about 0.05 to about 40 mg/ml, about 0.05 to about 50 mg/ml, about 0.05 to about 60 mg/ml, about 0.05 to about 80 mg/ml, about 5 mg/ml to 10 mg/ml, about 5 mg/ml to 20 mg/ml, about 5 mg/ml to about 40 mg/ml, about 5 mg/ml to 60 mg/ml, about 5 mg/ml to about 100 mg/ml, about 20 mg/ml to about 40 mg/ml, about 20 mg/ml to 60 mg/ml, or about 20 mg/ml to about 100 mg/ml.
  • the collagen composition is mixed in a single step with the buffer solution to polymerize the collagen.
  • the collagen composition is mixed with the buffer solution in the absence of magnesium or manganese ions to polymerize the collagen.
  • the collagen composition is mixed with the buffer solution to form the collagen solution and the collagen solution is incubated at a temperature greater than about 25 °C to promote polymerization of the collagen in the collagen solution.
  • the collagen solution can be incubated at about 37 °C to promote polymerization of the collagen in the collagen solution.
  • the collagen solution can be incubated at about 25 °C, 26 °C, 27 °C, 28 °C, 29 °C, 30 °C, 31 °C, 32 °C, 33 °C, 34 °C, 35 °C, 36 °C, 38 °C, 39 °C, or 40 °C, to promote polymerization of the collagen in the collagen solution.
  • the collagen solution can be incubated at from about 25 °C to about 40 °C to promote polymerization of the collagen in the collagen solution.
  • the polymerization can be conducted at temperatures above 20 °C, or at a temperature selected from the range of about 20 °C to about 40 °C. In these embodiments, the collagen can be polymerized to form fibrils similar to those found in the body.
  • the buffer solution to be mixed with the collagen in one embodiment, the buffer solution to be mixed with the collagen
  • composition to form the collagen solution can comprise about .03 mM to about 0.2 mM MgCl 2; about .002 mM to about .02 mM MgCl 2 , less than about .02 mM MgCl 2 , or no MgCl 2 .
  • the buffer solution to be mixed with the collagen composition to form the collagen solution can comprise about 0.3 mM to about 3 mM KH 2 P0 4 , about 1 mM to about 10 M Na 2 HP0 4 , about 0.1 mM to about 4 mM KC1, about .02 M to about 0.3 M NaCl, and about .002 N to about .02 N NaOH.
  • the buffer solution to be mixed with the collagen composition to form the collagen solution can comprise about 0.5 weight percent to about 5 weight percent of glucose, about 0.5 weight percent glucose or less, or no glucose.
  • the buffer solution can be diluted from a 10X, 5X, 2X, or any suitable starting concentration, to make a IX buffer solution having any of the component concentrations in the preceding paragraph.
  • the kit described herein can contain a buffer solution with a concentration of 10X, 5X, or 2X, or any suitable starting concentration, for dilution to make a IX buffer solution.
  • the 10X buffer solution can comprise the following ingredients at the following concentrations:
  • a IX buffer solution can comprise the following ingredients at the following concentrations:
  • NaOH is present in the buffer solution.
  • the NaOH was added separately as an additional mixing step in the methods for polymerization of collagen.
  • calcium chloride can be present in the buffer solution at a concentration of about 0.4 mM to about 2.0 mM.
  • the buffer in the buffer solution may be selected from the group consisting of phosphate buffer saline (PBS), Tris (hydroxymethyl) aminomethane Hydrochloride (Tris-HCl), 3-(N-Morpholino) Propanesulfonic Acid (MOPS), piperazine-n,n'- bis (2-ethanesulfonic acid) (PIPES), [n-(2-Acetamido)]-2-Aminoethanesulfonic Acid (ACES), N-[2-hydroxyethyl] piperazine-N'- [2-ethanesulfonic acid] (HEPES), and 1,3- bis[tris(Hydroxymethyl)methylamino]propane (Bis Tris Propane).
  • PBS phosphate buffer saline
  • Tris-HCl Tris (hydroxymethyl) aminomethane Hydrochloride
  • MOPS 3-(N-Morpholino) Propanesulfonic Acid
  • PBS phosphate buffer
  • the pH of the collagen solution for the polymerization of collagen is selected from the range of about 5.0 to about 11, about 6.0 to about 9.0, about 6.5 to about 8.5, and in another embodiment the pH is about 7.3 to about 7.4.
  • nutrients including minerals, amino acids, sugars, peptides, proteins, vitamins, or glycoproteins that facilitate cellular proliferation, such as laminin and fibronectin, hyaluronic acid, or growth factors such as epidermal growth factor, platelet-derived growth factor, transforming growth factor beta, or fibroblast growth factor, and glucocorticoids such as dexamethasone, can be added to the collagen solution before or after collagen polymerization is complete or during collagen polymerization.
  • growth factors such as epidermal growth factor, platelet-derived growth factor, transforming growth factor beta, or fibroblast growth factor, and glucocorticoids such as dexamethasone
  • cells can be added to the collagen solution before or after collagen polymerization is complete or during collagen polymerization.
  • the cells can be selected from the group consisting of epithelial cells, endothelial cells,
  • mesodermally-derived cells mesothelial cells, synoviocytes, neural cells, glial cells,
  • osteoblasts fibroblasts, chondrocytes, tenocytes, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, multi-potential progenitor cells (e.g., stem cells, including bone marrow progenitor cells), adipocytes, and osteogenic cells.
  • progenitor cells e.g., stem cells, including bone marrow progenitor cells
  • adipocytes e.g., adipocytes, and osteogenic cells.
  • a collagen matrix prepared according to the any of the methods described herein is provided.
  • the collagen matrix can be a medical graft.
  • the medical graft has a use selected from the group consisting of a tissue graft material, an injectable graft material, a wound dressing, a hemostatic dressing, a delivery vehicle for therapeutic cells, and a delivery vehicle for a therapeutic agent.
  • the methods described herein may be used to make a bioink formulation for printing tissues or organs.
  • the collagen matrix is used for research purposes, such as drug toxicity testing or drug development.
  • the matrices prepared by the methods described herein can serve as substrates for the regrowth of
  • endogenous tissues at the implantation site e.g., remodeling
  • the matrices can have the characteristics of the damaged or diseased tissues that they replace at the site of implantation or injection.
  • the matrices described herein can contain fibrils with a fibril area fraction (defined as the percent area of the total area occupied by fibrils in a cross-sectional surface of the matrix) or a fibril volume fraction (the percent area of the total area occupied by fibrils in 3 dimensions) of about 0.1% to about 100%, about 0.5% to about 100%, about 0.5% to about 26%, about 1% to about 100%, about 1% to about 26%, about 1% to about 7%, about 1% to about 15%, of about 7% to about 26%, about 20% to about 30%, about 20% to about 50%, about 20% to about 70%, about 20% to about 100%, about 30% to about 50%, about 30% to about 70%, or about 30% to about 100%, and/or a modulus (e.g., an elastic or linear modulus (defined by the slope of the linear region of the stress- strain curve obtained using conventional mechanical testing protocols; i.e., stiffness), a compressive modulus, or a shear storage modulus) of about 0.5
  • a modulus e.
  • a kit comprising lyophilized collagen, a hydrochloric acid solution, and a buffer solution is described.
  • a kit comprising a collagen composition and a buffer solution is provided.
  • the buffer solution can comprise about .03 mM to about 0.2 mM MgCl 2 , about .002 mM to about .02 mM MgCl 2 , less than about .02 mM MgCl 2 , or the buffer solution does not comprise MgCl 2 .
  • the buffer solution further comprises about .003 M to about .03 M
  • the buffer solution can comprise about 0.2 weight percent to about 5 weight percent of glucose, about 0.5 weight percent glucose or less, or no glucose.
  • the hydrochloric acid solution can comprise about .005 N hydrochloric acid to about 0.1 N hydrochloric acid.
  • the lyophilized collagen, the hydrochloric acid solution, and the buffer solution are in separate containers.
  • the collagen in the collagen composition can be at a concentration of about 0.1 mg/ml to about 40 mg/ml or about 0.1 mg/ml to about 5 mg/ml.
  • the collagen composition and the buffer solution can be in separate containers, such as sterilized vials or separate compartments of a dual syringe comprising a mixing element.
  • the kit can comprise instructions for use of components of the kit.
  • the buffer solution is capable of polymerizing collagen using a single mixing step comprising mixing the buffer solution with the lyophilized collagen reconstituted in the hydrochloric acid solution or with the collagen composition.
  • a kit is provided with collagen in a lyophilized form and the kit further comprises a buffer solution as described herein and a solution of an acid, such as acetic acid, or another dilute acid including for example, hydrochloric acid, formic acid, lactic acid, citric acid, sulfuric acid, or phosphoric acid for reconstituting the lyophilized collagen.
  • an acid such as acetic acid, or another dilute acid including for example, hydrochloric acid, formic acid, lactic acid, citric acid, sulfuric acid, or phosphoric acid for reconstituting the lyophilized collagen.
  • Type I collagen oligomers were derived from the dermis of closed herd pigs and prepared as described previously (Bailey JL, Critser PJ, Whittington C, Kuske JL, Yoder MC, Voytik-Harbin SL; Collagen oligomers modulate physical and biological properties of three- dimensional self-assembled matrices, Biopolymers (2011) 95(2):77-93 and Kreger ST, Bell BJ, Bailey J, Stites E, Kuske J, Waisner B, Voytik-Harbin SL; Polymerization and matrix physical properties as important design considerations for soluble collagen formulations, Biopolymers (2010) 93(8):690-707, both incorporated herein by reference).
  • lyophilized collagen oligomers Prior to use, lyophilized collagen oligomers were dissolved in 0.01 N hydrochloric acid. Research-grade oligomer was rendered aseptic by chloroform exposure at 4°C. Medical-grade oligomer was sterile filtered using a 0.22 ⁇ Millex-GP PES Express syringe filter (Millipore, SLGP033RS). A Sirius Red (Direct Red 80) assay was used to determine collagen concentration. Oligomer formulations were standardized based upon purity as well as polymerization capacity according to the ASTM international consensus standard F3089-14 (ASTM Standard F3089, 2014, "Standard Guide for Characterization and Standardization of Polymerizable Collagen-Based Products and
  • Polymerization capacity is defined by matrix shear storage modulus (G') as a function of collagen concentration of the polymerization reaction.
  • G' matrix shear storage modulus
  • Multi-step self-assembly was performed and involved 3 reagents— 10X Polymerization Buffer PLUS, 0.1N NaOH, and Polymerization Supplement.
  • Single-step self-assembly was performed with 10X self-assembly reagents (diluted 1:10) prepared according to the following recipe in the absence of MgCl 2 :
  • Integra Flowable was obtained from Integra Life Sciences (Plainsboro, NJ) and handled according to manufacturer's instructions.
  • Viscoelastic properties of self-assembled collagen matrices were determined using oscillatory shear mode on an AR2000 rheometer (TA Instruments, New Castle, DE) as previously described (Kreger et al., 2010). Samples were polymerized on the rheometer stage for 30 min followed by a shear-strain sweep from 0.1% to 4% strain at 1 Hz. The shear storage modulus (G') at 1% strain was used as a measure of matrix stiffness.
  • hASC Low-passage human adipose-derived stem cells
  • DMEM Dulbecco's Modified Eagle Medium
  • FBS fetal bovine serum
  • penicillin 100 U/mL penicillin
  • streptomyosin 100 U/mL streptomyosin
  • Cell-encapsulated collagen-fibril tissue constructs were prepared by suspending hASC (300,000 cells/ml) in neutralized oligomer (200 Pa) solutions. Neutralization was achieved using multi-step or single-step procedures and reagents. Tissue constructs were fixed in 3% paraformaldehyde after 3 days of culture and stained with phalloidin for visualization of the actin cytoskeleton. For 3D qualitative analysis, tissue constructs were imaged using an Olympus FluoView FV-1000 confocal system adapted to an inverted microscope (1X81, Olympus Corporation, Tokyo, Japan).
  • the single-step self-assembly procedure and reagent included maintenance of i) physiologically relevant conditions and reagents and ii) polymerization capacity as observed with an established multi-step procedure.
  • Initial attempts to combine all reagents used in a multi-step procedure including 10X Polymerization Buffer PLUS, Polymerization Supplement, and NaOH, resulted in an unstable solution that formed a flocculent precipitate.
  • MgCl 2 was removed, no precipitation was noted, even when stored at 4°C for extended periods of time. Based upon these results, follow-up studies were performed to evaluate the polymerization capacity and in vitro cell response.
  • oligomer represents a soluble molecular solution, it is amenable to sterile filtration. Oligomer formulation (500 Pa) showed statistically similar (p>0.05) polymerization kinetics and capacity before (458 ⁇ 55 Pa) and after (434 ⁇ 49) sterile filtration. Additional studies confirmed that similar in vivo tissue responses were obtained with research-grade and medical- grade oligomer formulations. Furthermore, the in-vivo tissue response obtained using single- step polymerization of research-grade oligomer was consistent with those obtained using multi- step polymerization procedures (see Fig. 5).
  • UVC Monochromatic ultraviolet radiation at 254nm

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021154845A1 (en) * 2020-01-27 2021-08-05 Geniphys, Llc Biologic filler for restoring and regenerating tissue
US11478574B2 (en) 2013-10-16 2022-10-25 Purdue Research Foundation Collagen compositions and methods of use
US11739291B2 (en) 2017-04-25 2023-08-29 Purdue Research Foundation 3-dimensional (3D) tissue-engineered muscle for tissue restoration
US11919941B2 (en) 2015-04-21 2024-03-05 Purdue Research Foundation Cell-collagen-silica composites and methods of making and using the same
US12274808B2 (en) 2014-08-27 2025-04-15 Purdue Research Foundation Collagen-based therapeutic delivery systems
US12280176B2 (en) 2017-01-31 2025-04-22 Geniphys, Inc. Methods and compositions for matrix preparation

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* Cited by examiner, † Cited by third party
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US11808760B1 (en) * 2019-02-14 2023-11-07 Curi Bio, Inc. System and methods for in vitro structural toxicity testing
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0443094A2 (en) 1990-02-15 1991-08-28 Darby & Darby P.C. Non-biodegradable, two-phase corneal implant and method for preparing same
US20080268052A1 (en) * 2006-09-21 2008-10-30 Voytik-Harbin Sherry L Collagen preparation and method of isolation
US20090280180A1 (en) 2007-12-10 2009-11-12 Voytik-Harbin Sherry L Collagen-based matrices with stem cells
US20120297550A1 (en) * 2007-06-12 2012-11-29 Musculoskeletal Transplant Foundation Process for sterilizing acellular soft tissue with irradiation
US20120297559A1 (en) 2011-05-27 2012-11-29 Hon Hai Precision Industry Co., Ltd. Object searching system, object searching method, and cleaning robot
US20150367030A1 (en) 2013-02-01 2015-12-24 Children's Medical Center Corporation Collagen scaffolds

Family Cites Families (163)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3949073A (en) 1974-11-18 1976-04-06 The Board Of Trustees Of Leland Stanford Junior University Process for augmenting connective mammalian tissue with in situ polymerizable native collagen solution
US4233360A (en) 1975-10-22 1980-11-11 Collagen Corporation Non-antigenic collagen and articles of manufacture
US4439521A (en) 1981-10-21 1984-03-27 Ontario Cancer Institute Method for producing self-reproducing mammalian pancreatic islet-like structures
US4582640A (en) 1982-03-08 1986-04-15 Collagen Corporation Injectable cross-linked collagen implant material
US4544516A (en) 1982-07-28 1985-10-01 Battelle Development Corporation Collagen orientation
US4801299A (en) 1983-06-10 1989-01-31 University Patents, Inc. Body implants of extracellular matrix and means and methods of making and using such implants
CA1295796C (en) 1984-03-27 1992-02-18 Conrad Whyne Biodegradable matrix and methods for producing same
US4789663A (en) 1984-07-06 1988-12-06 Collagen Corporation Methods of bone repair using collagen
US4743552A (en) 1984-09-26 1988-05-10 Sloan-Kettering Institute For Cancer Research Method for growth in tissue culture of normal colonic epithelial cells and method for determination of preneoplastic color cells
US4600533A (en) 1984-12-24 1986-07-15 Collagen Corporation Collagen membranes for medical use
US4829000A (en) 1985-08-30 1989-05-09 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Reconstituted basement membrane complex with biological activity
US5863531A (en) 1986-04-18 1999-01-26 Advanced Tissue Sciences, Inc. In vitro preparation of tubular tissue structures by stromal cell culture on a three-dimensional framework
US5032508A (en) 1988-09-08 1991-07-16 Marrow-Tech, Inc. Three-dimensional cell and tissue culture system
US5266480A (en) 1986-04-18 1993-11-30 Advanced Tissue Sciences, Inc. Three-dimensional skin culture system
GB8618374D0 (en) 1986-07-28 1986-09-03 Hsc Res Dev Corp Biological vascular prostheses
JPH0774239B2 (ja) 1986-09-04 1995-08-09 新田ゼラチン株式会社 細胞培養用高ゲル強度酸可溶性コラーゲンの製法
US5604106A (en) 1987-06-05 1997-02-18 Us Commerce Method for detecting carcinoma
JPH0728730B2 (ja) 1988-03-27 1995-04-05 新技術事業団 擬膵島および拡散チャンバー型人工膵臟
US4902508A (en) 1988-07-11 1990-02-20 Purdue Research Foundation Tissue graft composition
US4956178A (en) 1988-07-11 1990-09-11 Purdue Research Foundation Tissue graft composition
US4912057A (en) 1989-06-13 1990-03-27 Cancer Diagnostics, Inc. Cell chamber for chemotaxis assay
US5336616A (en) 1990-09-12 1994-08-09 Lifecell Corporation Method for processing and preserving collagen-based tissues for transplantation
US5163955A (en) 1991-01-24 1992-11-17 Autogenics Rapid assembly, concentric mating stent, tissue heart valve with enhanced clamping and tissue alignment
WO1992015676A1 (en) 1991-03-08 1992-09-17 The Salk Institute For Biological Studies Somatic cell gene therapy
DE69232535T4 (de) 1991-06-24 2003-09-11 Hcell Technology, Inc. In langzeitkultur gehaltene hormon-absondernde pankreatische zellen
FR2678624A1 (fr) 1991-07-04 1993-01-08 Coletica Utilisation de la peau non pigmentee de poisson, en particulier de poisson plat comme nouvelle source industrielle de collagene, procede d'extraction, collagene et biomateriau ainsi obtenus.
US5281422A (en) 1991-09-24 1994-01-25 Purdue Research Foundation Graft for promoting autogenous tissue growth
US5204382A (en) 1992-02-28 1993-04-20 Collagen Corporation Injectable ceramic compositions and methods for their preparation and use
US5428022A (en) 1992-07-29 1995-06-27 Collagen Corporation Composition of low type III content human placental collagen
US5478739A (en) 1992-10-23 1995-12-26 Advanced Tissue Sciences, Inc. Three-dimensional stromal cell and tissue culture system
US5641518A (en) 1992-11-13 1997-06-24 Purdue Research Foundation Method of repairing bone tissue
US5352463A (en) 1992-11-13 1994-10-04 Badylak Steven F Tissue graft for surgical reconstruction of a collagenous meniscus and method therefor
US5275826A (en) 1992-11-13 1994-01-04 Purdue Research Foundation Fluidized intestinal submucosa and its use as an injectable tissue graft
US5510263A (en) 1993-04-05 1996-04-23 Desmos, Inc. Growth of pancreatic islet-like cell clusters
US5460962A (en) 1994-01-04 1995-10-24 Organogenesis Inc. Peracetic acid sterilization of collagen or collagenous tissue
JPH0789564B2 (ja) 1994-04-12 1995-09-27 株式会社東芝 半導体装置の製造方法
US6475232B1 (en) 1996-12-10 2002-11-05 Purdue Research Foundation Stent with reduced thrombogenicity
US5709934A (en) 1994-11-22 1998-01-20 Tissue Engineering, Inc. Bipolymer foams having extracellular matrix particulates
US5695998A (en) 1995-02-10 1997-12-09 Purdue Research Foundation Submucosa as a growth substrate for islet cells
US6485723B1 (en) 1995-02-10 2002-11-26 Purdue Research Foundation Enhanced submucosal tissue graft constructs
US5916790A (en) 1995-03-03 1999-06-29 Metabolex, Inc. Encapsulation compositions, and methods
US5711969A (en) 1995-04-07 1998-01-27 Purdue Research Foundation Large area submucosal tissue graft constructs
US5554389A (en) 1995-04-07 1996-09-10 Purdue Research Foundation Urinary bladder submucosa derived tissue graft
US5776193A (en) 1995-10-16 1998-07-07 Orquest, Inc. Bone grafting matrix
US6419920B1 (en) 1995-10-25 2002-07-16 Trans Karyotic Therapies, Inc. Hybrid matrix implants and explants
AU736255B2 (en) 1995-10-25 2001-07-26 Shire Human Genetic Therapies, Inc. Hybrid matrix implants and explants
ATE258810T1 (de) 1995-11-09 2004-02-15 Univ Massachusetts Wiederherstellung der gewebeoberfläche mit zusammensetzungen aus hydrogel-zellen
US6497875B1 (en) 1996-04-26 2002-12-24 Case Western Reserve University Multilayer skin or dermal equivalent having a layer containing mesenchymal stem cells
ATE237371T1 (de) 1996-08-16 2003-05-15 Childrens Medical Center Blasenmukosa mit zellen für die rekonstruktion von geweben
US6171344B1 (en) 1996-08-16 2001-01-09 Children's Medical Center Corporation Bladder submucosa seeded with cells for tissue reconstruction
US6666892B2 (en) 1996-08-23 2003-12-23 Cook Biotech Incorporated Multi-formed collagenous biomaterial medical device
BR9711166A (pt) 1996-08-23 1999-08-17 Cook Biotech Inc PrÄtese de enxerto materiais para sua prepara-Æo e m-todos para seu uso
CA2263898C (en) 1996-09-16 2009-12-08 Purdue Research Foundation Composition and method for repairing neurological tissue
WO1998025636A1 (en) 1996-12-10 1998-06-18 Purdue Research Foundation Stomach submucosa derived tissue graft
AU743779B2 (en) 1996-12-10 2002-02-07 Cook Biotech, Inc. Tubular grafts from purified submucosa
US6375989B1 (en) 1996-12-10 2002-04-23 Purdue Research Foundation Submucosa extracts
CA2274033C (en) 1996-12-10 2010-05-11 Purdue Research Foundation Biomaterial derived from vertebrate liver tissue
WO1998052637A1 (en) 1997-05-23 1998-11-26 Biosense, Inc. Catheter with oblique lumen
CA2308146A1 (en) 1997-07-28 1999-02-04 Thomas B. Neff Collagen type i and type iii adhesive compositions
US6248587B1 (en) 1997-11-26 2001-06-19 University Of Southern Cailfornia Method for promoting mesenchymal stem and lineage-specific cell proliferation
WO1999043786A2 (en) 1998-02-27 1999-09-02 Purdue Research Foundation Submucosa gel compositions
DE19812713A1 (de) 1998-03-24 1999-09-30 Merck Patent Gmbh Verfahren zur Herstellung von mineralisierten Kollagenfibrillen und deren Verwendung als Knochenersatzwerkstoff
JP2002525043A (ja) 1998-09-11 2002-08-13 パーデュー・リサーチ・ファウンデーション 改良粘膜下組織グラフト構成物
ATE305967T1 (de) 1998-11-19 2005-10-15 Organogenesis Inc Biotechnisch konstruiertes gewebe und verfahren zu dessen produktion und benutzung
US6918396B1 (en) 1998-12-01 2005-07-19 Purdue Research Foundation Method for vocal cord reconstruction
ES2353728T3 (es) 1999-02-10 2011-03-04 Curis, Inc. Péptido yy (pyy) para tratar trastornos metabólicos de la glucosa.
US6592623B1 (en) 1999-08-31 2003-07-15 Virginia Commonwealth University Intellectual Property Foundation Engineered muscle
US7615373B2 (en) 1999-02-25 2009-11-10 Virginia Commonwealth University Intellectual Property Foundation Electroprocessed collagen and tissue engineering
US20050153442A1 (en) 1999-03-10 2005-07-14 Adam Katz Adipose-derived stem cells and lattices
WO2000062833A1 (en) 1999-04-15 2000-10-26 The Research Foundation Of State University Of New York Cellular matrix system and use thereof
WO2001010355A1 (en) 1999-08-06 2001-02-15 Cook Biotech Incorporated Tubular graft construct
US6592794B1 (en) 1999-09-28 2003-07-15 Organogenesis Inc. Process of making bioengineered collagen fibrils
ATE428768T1 (de) 1999-09-28 2009-05-15 Organogenesis Inc Biotechnische kollagenfibrillen
US6482240B1 (en) 1999-12-07 2002-11-19 Ed. Geistlich Soehne Ag Fur Chemische Industrie Method of making a collagen membrane from porcine skin
US6576265B1 (en) 1999-12-22 2003-06-10 Acell, Inc. Tissue regenerative composition, method of making, and method of use thereof
CA2393468C (en) 1999-12-22 2012-03-20 Acell, Inc. Tissue regenerative composition
US6479064B1 (en) 1999-12-29 2002-11-12 Children's Medical Center Corporation Culturing different cell populations on a decellularized natural biostructure for organ reconstruction
US20020039788A1 (en) 2000-02-29 2002-04-04 Isseroff Roslyn R. Corneal epithelial graft composites
ES2288946T3 (es) 2000-04-14 2008-02-01 University Of Pittsburgh Aumento y abultamiento de tejido blando y hueso utilizando celulas progenitoras derivadas de musculo, sus composiciones y tratamientos.
US6893812B2 (en) 2000-05-30 2005-05-17 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Three-dimensional ex vivo angiogenesis system
CA2410956C (en) 2000-05-31 2012-12-04 Michaela Noll Three-dimensional skin model
DE20019809U1 (de) 2000-05-31 2001-07-12 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., 80636 München Knorpelersatz und Biomatrix zur Kultivierung von Zellen
CZ301649B6 (cs) 2000-06-28 2010-05-12 Ed. Geistlich Soehne Ag Fur Chemische Industrie Incorporated Under The Laws Of Switzerland Trubice pro regeneraci nervu a zpusob jejich výroby
DE10032610C2 (de) 2000-07-07 2003-05-15 Fischer W Mueller Blasformtech Verfahren zum Herstellen von Kunststoff-Blasformartikeln
HUP0300810A2 (hu) 2000-07-20 2003-08-28 M.G.V.S. Ltd. Mesterséges értranszplantátum, valamint ennek létrehozása és alkalmazása
AU2001284968B2 (en) 2000-08-16 2006-12-21 Duke University Decellularized tissue engineered constructs and tissues
AU2001291543A1 (en) 2000-09-06 2002-03-22 Germain, Lucie In vitro human angiogenesis model
US20020076816A1 (en) 2000-12-04 2002-06-20 Jianwu Dai Stem cells and signals developed for use in tissue and organ repair and replacement
US6586493B1 (en) 2001-03-07 2003-07-01 Arizona Board Of Regents Arizona State University Polysaccharide-based hydrogels and pre-gel blends for the same
US7029689B2 (en) 2001-05-10 2006-04-18 Georgia Tech Research Corporation Tubular construct for implantation
CA2388723C (en) 2001-06-06 2012-10-23 Becton, Dickinson & Company Method of providing a substrate with a ready-to-use, uniformly distributed extracellular matrix
US20030078653A1 (en) 2001-06-15 2003-04-24 Ivan Vesely Tissue engineered mitral valve chordae and methods of making and using same
EP1270672B1 (en) 2001-06-28 2007-11-14 PV Industries B.V. Process for recovering native collagen
US7087089B2 (en) 2001-06-28 2006-08-08 Cook Biotech Incorporated Graft prosthesis devices containing renal capsule collagen
WO2003020955A2 (en) 2001-08-31 2003-03-13 Pacgen Cellco Llc Use of recipient endothelial cells for enhanced vascularization of tissue and tissue-engineered construct transplants
DE20115753U1 (de) 2001-09-14 2002-01-10 Institut für Agrar- und Stadtökologische Projekte an der Humboldt-Universität zu Berlin, 10115 Berlin Lösliche Kollagene
AU2003202261A1 (en) 2002-01-11 2003-07-30 Purdue Research Foundation Biomaterial derived from vertebrate liver tissue
US8394371B2 (en) 2002-02-11 2013-03-12 Neocutis Sa Compositions for the treatment of skin conditions, disorders or diseases and methods of making and using the same
US20060014284A1 (en) 2002-03-21 2006-01-19 Thomas Graeve Biomatrix and method for producting the same
AU2003241291A1 (en) 2002-04-12 2003-10-27 Yale University Vascularized human skin equivalent
CN1665527A (zh) 2002-05-02 2005-09-07 普渡研究基金会 血管化增强的移植构造物
CN1713861A (zh) 2002-05-02 2005-12-28 普渡研究基金会 血管化增强的移植构造物
NZ536563A (en) 2002-05-02 2008-03-28 Purdue Research Foundation Vascularization enhanced graft constructs
CA2484614A1 (en) 2002-05-02 2003-11-13 Cook Biotech Incorporated Cell-seeded extracellular matrix grafts
AUPS242702A0 (en) 2002-05-21 2002-06-13 Colltech Australia Limited Improved method for the extraction and purification of collagen
AU2003279730A1 (en) 2002-09-30 2004-04-19 Fibrogen, Inc. Dry tissue sealant compositions
US20040126405A1 (en) 2002-12-30 2004-07-01 Scimed Life Systems, Inc. Engineered scaffolds for promoting growth of cells
EP1605862A4 (en) 2003-02-28 2008-09-03 Fibrogen Inc COLLAGEN COMPOSITIONS AND BIOMATERIALS
WO2005003300A2 (en) 2003-06-04 2005-01-13 University Of South Carolina Tissue scaffold having aligned fibrils, apparatus and method for producing same, and methods of using same
US20050014181A1 (en) 2003-06-18 2005-01-20 Galis Zorina S. Methods and compositions for the assessment of polymer assembly
US8741352B2 (en) 2003-08-25 2014-06-03 Cook Biotech Incorporated Graft materials containing ECM components, and methods for their manufacture
US8043614B2 (en) 2004-03-09 2011-10-25 Ahlfors Jan-Eric W Autogenic living scaffolds and living tissue matrices: methods and uses thereof
US8337545B2 (en) 2004-02-09 2012-12-25 Cook Medical Technologies Llc Woven implantable device
CA2554094A1 (en) 2004-02-09 2005-08-25 Indiana University Research And Technology Corporation Isolation, expansion and use of clonogenic endothelial progenitor cells
WO2005081970A2 (en) 2004-02-24 2005-09-09 The Curators Of The University Of Missouri Self-assembling cell aggregates and methods of making engineered tissue using the same
US20050260748A1 (en) 2004-02-27 2005-11-24 Michigan State University Adult stem cells and uses thereof
GB0415080D0 (en) 2004-07-05 2004-08-04 Ucl Biomedica Plc Methods for preparing tissue equivalent implants and products thereof
WO2006030442A2 (en) 2004-09-16 2006-03-23 Gamida-Cell Ltd. Methods of ex vivo progenitor and stem cell expansion by co-culture with mesenchymal cells
US8337873B2 (en) 2004-10-22 2012-12-25 The Board Of Trustees Of The University Of Illinois Hollow and porous orthopaedic or dental implant that delivers a biological agent
WO2006060779A2 (en) 2004-12-03 2006-06-08 Case Western Reserve University Novel methods, compositions and devices for inducing neovascularization
US20060134072A1 (en) 2004-12-22 2006-06-22 Pedrozo Hugo A Self-assembling protein matrix prepared from natural extracellular matrices
US8728463B2 (en) 2005-03-11 2014-05-20 Wake Forest University Health Science Production of tissue engineered digits and limbs
CA2603116A1 (en) 2005-03-29 2006-10-05 The Regents Of The University Of California Controlling stem cell destiny with tunable network
CA2608422C (en) 2005-05-16 2014-10-28 Purdue Research Foundation Engineered extracellular matrices control stem cell behavior
CA2608708C (en) 2005-05-16 2014-04-22 Purdue Research Foundation Engineered extracellular matrix having a specified fibril area fraction
WO2007028079A2 (en) 2005-09-01 2007-03-08 Duke University Methods of stimulating expansion of hematopoietic stem cells
GB0524048D0 (en) 2005-11-25 2006-01-04 Ucl Biomedica Plc Bio-artificial materials with tuneable properties
US20070190646A1 (en) 2006-02-10 2007-08-16 The Trustees Of The University Of Pennsylvania Regulating stem cell differentiation by controlling matrix elasticity
US20070269476A1 (en) 2006-05-16 2007-11-22 Voytik-Harbin Sherry L Engineered extracellular matrices control stem cell behavior
WO2007136634A1 (en) 2006-05-16 2007-11-29 Purdue Research Foundation Three dimensional purified collagen matrices
US20080026032A1 (en) 2006-07-27 2008-01-31 Zubery Yuval Composite implants for promoting bone regeneration and augmentation and methods for their preparation and use
EP2076279B1 (en) 2006-10-06 2014-08-27 Anthrogenesis Corporation Native (telopeptide) placental collagen compositions
EP2091335A4 (en) 2006-11-09 2012-07-04 Gamida Cell Ltd USE OF EX VIVO CULTIVATED HEMATOPOIETIC CELLS IN THE TREATMENT OF ACROSYNDROMES
US20100143476A1 (en) 2007-02-14 2010-06-10 March Keith L Composition for stimulating formation of vascular structures
US20100272697A1 (en) 2007-04-10 2010-10-28 Ali Naji Pancreatic islet cells composition and methods
WO2008131293A2 (en) 2007-04-19 2008-10-30 Collengin, Inc. Oriented collagen-based materials, films and methods of making same
GB0713079D0 (en) 2007-07-05 2007-08-15 Ucl Business Plc biomaterial scaffolds with defined stiffness
AU2008331099B2 (en) 2007-11-26 2013-10-24 Collplant Ltd. Compositions comprising fibrous polypeptides and polysaccharides
CN102089425A (zh) 2008-05-07 2011-06-08 Ucl商业有限公司 仿生细胞支架
US20100119578A1 (en) 2008-11-07 2010-05-13 Specialized Vascular Technologies, Inc. Extracellular matrix modulating coatings for medical devices
WO2010123928A1 (en) 2009-04-20 2010-10-28 Purdue Research Foundation Collagen-based matrices for vessel density and size regulation
US9744123B2 (en) 2009-06-30 2017-08-29 Kensey Nash Corporation Biphasic implant device providing gradient
US20120115222A1 (en) 2009-07-16 2012-05-10 Purdue Research Foundation Composition and method for maintenance, differentiation, and proliferation of stem cells
GB0912399D0 (en) 2009-07-16 2009-08-26 Ucl Business Plc Polymeric collagen biomaterials
US8652500B2 (en) 2009-07-22 2014-02-18 Acell, Inc. Particulate tissue graft with components of differing density and methods of making and using the same
CN102131403B (zh) 2009-07-27 2014-06-04 成功大学 高纯度胶原蛋白的制备
WO2011019822A2 (en) 2009-08-11 2011-02-17 The Johns Hopkins University Compositions and methods for implantation of processed adipose tissue and processed adipose tissue products
WO2011064773A1 (en) 2009-11-24 2011-06-03 Collplant Ltd. Method of generating collagen fibers
US8475824B2 (en) 2010-01-26 2013-07-02 Warsaw Orthopedic, Inc. Resorbable matrix having elongated particles
ES2790628T3 (es) 2010-06-10 2020-10-28 Ucl Business Plc Aparatos, kits y métodos para la producción de construcciones biomiméticas
GB201011476D0 (en) 2010-07-07 2010-08-25 Ucl Business Plc Controlled production of biomaterial
US20120027732A1 (en) 2010-07-27 2012-02-02 Voytik-Harbin Sherry L Thermoreversible collagen
WO2012167249A2 (en) 2011-06-02 2012-12-06 Indiana University Research And Technology Corporation Materials and methods for controlling vasculogenesis from endothelial colony forming cells
FR2975922B1 (fr) 2011-06-06 2013-05-31 Arkema France Reacteur a plaques avec injection in situ
US20140056865A1 (en) 2012-08-17 2014-02-27 Allosource Adipose composition systems and methods
US20140193477A1 (en) 2012-10-11 2014-07-10 Emory University Collagen based materials and uses related thereto
GB201314312D0 (en) 2013-08-09 2013-09-25 Regentec Ltd Composition and delivery system
US9878071B2 (en) 2013-10-16 2018-01-30 Purdue Research Foundation Collagen compositions and methods of use
AU2015301432B2 (en) 2014-08-15 2019-11-21 The Johns Hopkins University Composite material for tissue restoration
EP3185922B1 (en) 2014-08-27 2025-04-02 Purdue Research Foundation Collagen-based therapeutic delivery systems
EP4201413A1 (en) 2015-09-10 2023-06-28 Symbiocelltech, LLC Neo-islets comprising stem and islet cells and treatment of diabetes mellitus therewith
CN110446500B (zh) 2017-01-31 2024-11-26 格尼菲斯公司 用于基质制备的方法和组合物
WO2019023266A1 (en) 2017-07-25 2019-01-31 Purdue Research Foundation ENCAPSULATION OF COLLAGEN OF CELLS PRODUCING INSULIN

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0443094A2 (en) 1990-02-15 1991-08-28 Darby & Darby P.C. Non-biodegradable, two-phase corneal implant and method for preparing same
US20080268052A1 (en) * 2006-09-21 2008-10-30 Voytik-Harbin Sherry L Collagen preparation and method of isolation
US20120297550A1 (en) * 2007-06-12 2012-11-29 Musculoskeletal Transplant Foundation Process for sterilizing acellular soft tissue with irradiation
US20090280180A1 (en) 2007-12-10 2009-11-12 Voytik-Harbin Sherry L Collagen-based matrices with stem cells
US20120297559A1 (en) 2011-05-27 2012-11-29 Hon Hai Precision Industry Co., Ltd. Object searching system, object searching method, and cleaning robot
US20150367030A1 (en) 2013-02-01 2015-12-24 Children's Medical Center Corporation Collagen scaffolds

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
MENTOR ET AL., PHOTO DERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, 2001
MIYATA ET AL., BIOCHEM.
RUCHA, DESIGNER COLLAGEN-FIBRIL BIOGRAFT MATERIALS FOR TUNABLE MOLECULAR DELIVERY, 1 January 2016 (2016-01-01)
See also references of EP3576775A4

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11478574B2 (en) 2013-10-16 2022-10-25 Purdue Research Foundation Collagen compositions and methods of use
US12274808B2 (en) 2014-08-27 2025-04-15 Purdue Research Foundation Collagen-based therapeutic delivery systems
US11919941B2 (en) 2015-04-21 2024-03-05 Purdue Research Foundation Cell-collagen-silica composites and methods of making and using the same
US12280176B2 (en) 2017-01-31 2025-04-22 Geniphys, Inc. Methods and compositions for matrix preparation
US11739291B2 (en) 2017-04-25 2023-08-29 Purdue Research Foundation 3-dimensional (3D) tissue-engineered muscle for tissue restoration
US12398368B2 (en) 2017-04-25 2025-08-26 Purdue Research Foundation 3-dimensional (3D) tissue-engineered muscle for tissue restoration
WO2021154845A1 (en) * 2020-01-27 2021-08-05 Geniphys, Llc Biologic filler for restoring and regenerating tissue
JP2023511628A (ja) * 2020-01-27 2023-03-20 ジェニフィス，インコーポレイテッド 組織を回復および再生させるための生物学的充填剤

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US20200246507A1 (en) 2020-08-06
EP3576775B1 (en) 2025-06-25
CN110446500B (zh) 2024-11-26
JP2020505474A (ja) 2020-02-20
US12280176B2 (en) 2025-04-22
CN110446500A (zh) 2019-11-12
ES3040675T3 (en) 2025-11-04
JP7242553B2 (ja) 2023-03-20

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