+

WO1999007777A1 - Substrat bioactif a base de verre - Google Patents

Substrat bioactif a base de verre Download PDF

Info

Publication number
WO1999007777A1
WO1999007777A1 PCT/US1998/016470 US9816470W WO9907777A1 WO 1999007777 A1 WO1999007777 A1 WO 1999007777A1 US 9816470 W US9816470 W US 9816470W WO 9907777 A1 WO9907777 A1 WO 9907777A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
glass
polymer
matrix
cells
Prior art date
Application number
PCT/US1998/016470
Other languages
English (en)
Inventor
Guy Latorre
Sean Lee
Jipin Zhong
Al Fosmoe
Original Assignee
Us Biomaterials Corporation
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 Us Biomaterials Corporation filed Critical Us Biomaterials Corporation
Priority to AU88251/98A priority Critical patent/AU8825198A/en
Publication of WO1999007777A1 publication Critical patent/WO1999007777A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/40—Glass

Definitions

  • the present application relates to porous materials that can be used as three dimensional substrates on which to grow certain cell lines in culture and to the use of such substrates in medical practice.
  • a population of viable cultured cells are seeded into a porous, solid, biodegradable substrate. As the cells grow into and throughout this three-dimensional substrate, they lay down the extracellular matrix proteins and other molecules which eventually become a solid tissue implant material. The original substrate material will eventually be totally resorbed, either at the time of implant or sometime thereafter, so that only the generated extracellular matrix (and if desired, the cells) will remain.
  • tissue culture matrix is where dermal fibrob lasts are cultured in a polyglycolic acid (P G A) sponge to grow a collagen dermal equivalent for implants onto the skin, e.g., DermaGraft dermal implant material (supplied by Advanced Tissue Sciences). Chondrocytes may be cultured into the same material to produce artificial articular cartilage.
  • P G A polyglycolic acid
  • the desirable characteristics for a tissue growth substrate are that it (1) be resorbable within an appropriate time frame, (2) provide a desirable chemical environment for cell attachment, growth and/or activity, (3) have appropriate pore structure and/or surface texture for cell infiltration and (4) act as a suitable contact guidance system for cell migration and extracellular matrix deposition.
  • An acidic polymer such as a polylactic acid/polyglycolic acid (P L A/P G A) growth substrate, is that it lowers the pH of the medium substantially as it degrades, thereby inhibiting cell growth and activity. Allogeneic/xenogeneic collagen sponge substrates are sometimes used as well, however, there are difficulties associated with disease transmission, potential host immunological response, handling and mechanical properties as well as cellular interactions.
  • Bioglass® is a biologically active synthetic material that includes varying compositions of SiO 2 , P 2 O5 ' CaO, and Na2 ⁇ (e.g. see L.L. Hench, et al., '"Biological Applications of Bioactive Glasses," Life Chemistry Reports, 13, 187- 241 (1996) and L.L. Hench, et al, Ed.s, An Introduction to Bioceramics, World Scientific, New York (1993)), has been shown in numerous in vitro and in vivo studies to be a bio-compatible surface for cell growth and activity. Bioglass® interacts with the host environment by a series of chemical reactions involving ion exchange and precipitation of mineral layers onto the surface. Melt-derived
  • Bioglass® particles by themselves have been shown in vitro to raise the pH of the medium depending on composition and particle size.
  • Sol-gel derived Bioglass® particles and fibers by contrast, contain no sodium and do not increase the pH of the host medium as it reacts as significantly as melt-derived Bioglass® particles.
  • melt-derived Bioglass® which has been pre-reacted in buffer solution for a specified amount of time may also maintain a more stable pH environment.
  • compositions useful for growing tissue including bone, and methods of preparation and use thereof, are disclosed.
  • the composition includes a biologically active material formed from oxides of silicon, phosphorus, sodium, and calcium, dispersed within a biodegradable polymer sponge material to form a three dimensional matrix.
  • the composition includes porous meshes that include spun fibers of a biologically active material that includes oxides of silicon, phosphorus, sodium, and calcium to form a three dimensional matrix.
  • the composition includes porous ceramic materials produced by sintering a biologically active glass powder, either as a sol-gel, melt- derived or pre-reacted melt derived form. This sintered material forms a porous three-dimensional matrix, which maintains a controllable pH as it reacts in the environment.
  • the porous materials described herein are ideally suited for applications such as tissue engineering which benefit from a high degree of porosity.
  • the polymer matrix includes biodegradable polymeric materials.
  • Suitable biodegradable polymers include polyhydroxy acids such as polylactic acid, polyglycolic acid and copolymers thereof, polyorthoesters, polysaccharides, proteins, polyanhydrides, polyphosphazenes, and copolymers and blends thereof.
  • the percent by weight of the glass composition to polymer is between 5 and 95%.
  • the porosity of the glass is between 0 and 85%.
  • the composition and any articles of manufacture that include the composition may or not be porous, and preferably has an overall porosity between about 0 and 80%.
  • compositions can optionally include additional components, such as non-degradable polymers, various biologically active substances such as growth factors (including TGF- ⁇ , basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), transforming growth factors ⁇ and ⁇ (TGF ⁇ and ⁇ ), platelet-derived growth factor (PDGF), and vascular endothelial growth factor/vascular permability factor (VEGF/VPF)), antivirals, antibacterials, antiinflammatories, immunosuppressants, analgesics, vascularizing agents, cell adhesion molecules (CAM's), bone mo hologenic proteins (BMP's) and anticoagulants.
  • growth factors including TGF- ⁇ , basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), transforming growth factors ⁇ and ⁇ (TGF ⁇ and ⁇ ), platelet-derived growth factor (PDGF), and vascular endothelial growth factor/vascular permability factor (VEGF/VPF)
  • growth factors
  • compositions can be in any suitable form for administration to a patient, such as sheets, screws, stents, pins, sutures, prosthetics, valves, plates, tubes and the like, or may be moldable or machinable.
  • compositions can be used as substrates to promote the growth of tissue, including bone, in vitro, ex vivo and/or in vivo.
  • compositions useful for growing tissue, including bone, and methods of preparation and use thereof are disclosed.
  • the composition includes a biologically active material formed from oxides of silicon, phosphorus, sodium, and calcium, dispersed within a biodegradable polymer sponge material to form a three dimensional matrix.
  • the composition includes porous meshes that include spun fibers of a biologically active material that includes oxides of silicon, phosphorus, sodium, and calcium to form a three dimensional matrix.
  • the composition includes porous ceramic materials produced by sintering a biologically active glass powder, either as a sol-gel or pre- reacted melt derived form. This sintered material forms a porous three-dimensional matrix, which may be tailored to maintain a desirable pH as it reacts in the environment of use.
  • compositions are superior to prior bioactive compositions used in cell culture.
  • bioactive glass alone does not provide for the superior structure obtainable when the combination of bioactive glass and a biodegradable polymer are used to provide a three dimensional cell culture media.
  • polymers in the composition allows for a greater range of available structures.
  • biodegradable refers to any material that is capable of being decomposed by natural biological processes, including those occurring in vivo or in vitro.
  • bioactive glass refers to any glass composition capable of eliciting a specific biological response at the interface of the material which results in the formation of a bond between the tissue and the material. This typically includes any bioactive glass composite material that includes, at least, silicon oxide, phosphorus oxide, calcium oxide and sodium oxide, in various proportions.
  • three dimensional matrix suitable for cell growth is intended to mean any porous structure comprising a bioactive glass dispersed within a biodegradable polymer capable of culturing cells.
  • the three dimensional matrix may, in some applications, be implanted into a patient. In other applications, the three dimensional matrix may be used only as an ex vivo platform for cell growth.
  • the glass preferably includes between 40 and 86%> by weight of silicon dioxide oxide (SiO 2 ), between about 0 and 30%> by weight of sodium oxide (Na 2 O), between about 4 and 46%> by weight calcium oxide (CaO), and between about 1 and 15%) by weight phosphorus oxide (P 2 O5). More preferably, the glass includes between 40 and 60% by weight of silicon dioxide oxide (SiO 2 ), between about 5- 30%) by weight of sodium oxide (Na 2 O), between about 10 and 35% by weight calcium oxide (CaO), and between about 1 and 12%> by weight phosphorus oxide (P 2 O5).
  • the oxides can be present as solid solutions or mixed oxides, or as mixtures of oxides.
  • CaF 2 , B 2 O 3 , Al 2 O 3 , MgO and K 2 O may be included in the composition in addition to silicon, sodium, phosphorus and calcium oxides.
  • the glass is preferably present as a porous material.
  • the pore size is between about 0 and 500 ⁇ m, preferably between about 10 and 150 ⁇ m, and more preferably, between about 50 and 100 ⁇ m.
  • the degree of porosity of the glass is between about 0 and 85 %, preferably between about 30 and 80 %>, and more preferably, between about 40 and 60 %.
  • the most preferred glass is Bioglass®TM (a trademark of University of Florida), which has a composition including about 45%> by weight silicon dioxide, about 24.5%) by weight sodium oxide, about 6% by weight phosphorus oxide, and about 24.5%o by weight calcium oxide.
  • Another preferred material is hydroxyapatite.
  • Biologically active glass-based substrates for tissue engineering are advantageous because they apparently readily incorporate and promote the production of collagen and other extracellular matrix proteins in vitro and in vivo, although the exact mechanism for this effect is not yet known.
  • the polymer matrix includes biodegradable polymeric materials.
  • Suitable biodegradable polymers include polyhydroxy acids such as polylactic acid, polyglycolic acid and copolymers thereof, polycarbonates, polyorthoesters, polysaccharides, proteins, polyanhydrides, polyphosphazenes, and copolymers and blends thereof.
  • biodegradable polymer depends on several factors, including the desired degradation time, the physical properties, including melting temperature and hardness, and chemical properties (i.e., the interaction of the polymeric materials with other components in the composition).
  • Preferred polymers include polylactic acid, polyglycolic acid, and copolymers and blends thereof.
  • the polymer preferably includes carboxylic acid functional groups, or includes anhydride or ester bonds which, upon hydrolysis, provide carboxylic acid functional groups. These groups assist in adhesion of cells to the polymer, which is desirable in a composition used for cell culture. Further, cell adhesion peptides, such as arginine-glycine-aspartic acid (RGD) can be incorporated into the polymer matrix or covalently linked to the polymers to assist with adhesion of cells to the polymer matrix.
  • RGD arginine-glycine-aspartic acid
  • the polymer is preferably present as a porous material, i.e., a porous polymer foam.
  • the pore size is between about 0 and 1,000 ⁇ m, preferably between about 100 and 800 ⁇ m, and more preferably, between about 200 and 500 ⁇ m.
  • the degree of porosity of the polymer is between about 0 and 85 %>, preferably between about 30 and 80 %, and more preferably, between about 40 and 60 %>.
  • Those of skill in the art can select an appropriate porosity taking into consideration the type of cells to be seeded, and the requisite dimensional stability of the composition.
  • the dimensional stability requirements are a function of how the composition will be used. If the composition is to be used as a three dimensional in vitro cell culture or a tissue engineering platform, the mechanical properties (e.g.
  • compositions can optionally include additional components, such as non-degradable polymers, various biologically active substances, and structural components.
  • Non-degradable polymers are preferably those that do not cause a non- desirable effect when implanted in vivo.
  • Suitable non-degradable polymers include polyacrylates such as polymethyl methacrylate (PMMA), polysulfones, polystyrene, polyalkylene oxides such as polyethylene oxide and polyethylene oxide/polypropylene oxide copolymers (PluronicsTM), polyvinyl alcohol, polyolefins such as polypropylene and polyethylene, polytetrafluoroethylene (TeflonTM).
  • Suitable biologically active substances specifically include those which promote healing and regulate cell/tissue growth, including bone growth.
  • Such substances include, but are not limited to, growth factors (including TGF- ⁇ , basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), transforming growth factors and ⁇ (TGF and ⁇ ), platelet-derived growth factor (PDGF), and vascular endothelial growth factor/vascular permability factor (VEGF/VPF)), antivirals, antibacterials, antiinflammatories, immunosuppressants, analgesics, vascularizing agents, cell adhesion molecules (CAM's), bone morphologenic proteins (BMP's), anticoagulants, nutrients, antivirals, antibacterials, antiinflammatories, immunosuppressants, and analgesics.
  • growth factors including TGF- ⁇ , basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), transforming growth factors and ⁇ (TGF and ⁇ ), platelet-derived growth factor
  • the composition includes a shape-memory polymer or metal alloy, such as TiNi, such that the composition can flex and return to its original position while bone or other cells/tissues are growing into the composition.
  • a shape-memory polymer or metal alloy such as TiNi, such that the composition can flex and return to its original position while bone or other cells/tissues are growing into the composition.
  • the composition can be used to grow several different types of tissue.
  • Bone tissue can be grown by seeding cells such as osteoprogenitor cells, bone marrow cell preparations, cells of osteoblastic phenotypic potential or of osteoblastic phenotypes.
  • the matrix prepared from the composition can also be seeded, for example, with fibroblasts and chondrocytes.
  • the matrix is seeded with cells from the patient to be treated to avoid problems associated with tissue rejection.
  • the cells are isolated from another human or from an animal source suitable for xenotransplantation into a human.
  • the cell seeding density is a function of the cell type being cultured. For most cells, typical cell densities range from between about 10 and 10 cells per cm 3. For example, chondrocytes are typically seeded at a density of about 4 X 105 cells per cm .
  • Suitable cell types that can be seeded include adipose cells, epithelial cells, endothelial cells, hepatocytes, smooth muscle cells, neurons, osteoclasts, chondrocytes, skin cells, mesenchymal cells, islet cells, keratinocytes, blood cells, mast cells, myocytes, stem cells and T cells.
  • the glass and polymer are combined to form a composite material that include both the glass and polymeric elements and which also optionally includes cells and other bioactive materials such that the composite can be used to grow cells and tissue, including bone tissue.
  • the pores of the composite material can be controlled in manufacturing to yield desirable size ranges for cell migration, such as between about 5 and 25 ⁇ m to enhance cell migration, and between about 400 and 500 ⁇ m to accomodate ingrowth of a cappilary bed system.
  • the material is not flat, but rather, is three dimensional, to allow for cell growth.
  • the composite material is preferably arranged in a manner which mimics the fiber density and orientation of the target tissue, yielding an implant whose mechanical properties match those of the surrounding tissue.
  • the composite material preferably includes melt-derived biologically active glass particles, such as Bioglass® (trademark of University of Florida), and PLA, PGA or copolymers and blends thereof.
  • the composite material is fully resorbable over time, with a resorption rate depending on the exact composition of the material. Because melt-derived Bioglass® tends to raise the pH of the medium as it reacts, this tends to buffer the pH change from the polymer degradation.
  • the buffering effect as well as the total degradation time depend upon the relative amounts of, and composition of, both the polymer and glass particulate in the material, as well as the pore texture of the composite material.
  • the rate of degradation, effect of the composition on the surrounding pH and the corresponding ion release rate can be controlled. Those of skill in the art can readily optimize the composition to allow for optimal cell migration, activity, degradation time and final growth of the artificial tissue at a stable pH.
  • the glass is in the form of spun fibers of Sol-gel derived or melt-derived Bioglass®. These fibers may be conglomerated in some fashion to yield a network with an average spacing between fibers equal to the target pore size for cell migration and matrix deposition.
  • the fibers can, but need not, include a biodegradable polymer.
  • the glass is in the form of sintered glass particles, preferably sintered particles of bioactive glass. The particles may be in sol-gel derived, or pre-reacted melt derived form.
  • compositions can be used for several purposes, including in vitro and ex vivo production of cells and tissue, including bone tissue, or for in vivo uses.
  • the material is preferably in the form of a sheet, a foam, or other shape suitable for tissue culture in vitro.
  • the material is not flat, but rather, is three dimensional, to allow for cell growth.
  • the material can be shaped to fit a particular defect, for example a bone defect, thus allowing bone or other tissue to grow through the material and fill the defect.
  • the composition can be used to correct a bone defect, or otherwise implanted where tissue growth, including bone growth, is desirable.
  • suitable forms for the composition include sheets, screws, stents, pins, sutures, prosthetics, valves, plates, tubes and the like.
  • the glass composition can be prepared in several ways, to provide melt- derived glass, spun fibers of sol-gel derived glass, and sintered glass particles.
  • the sintered particles may be in sol-gel derived, or pre-reacted melt derived form.
  • Sol- gel derived glass is generally prepared by synthesizing an inorganic network by mixing metal alkoxides in solution, followed by hydrolysis, gelation, and low temperature (600-900 °C) firing to produce a glass.
  • Melt derived glass is generally prepared by mixing grains of oxides or carbonates, melting and homogenizing the mixtures at high temperatures, typically between about 1250 and 1400°C. The molten glass can be fritted and milled to produce a powder or casted into steel or graphite molds to make bulk implants.
  • the glass composition is preferably melt-derived. In each preparation, it is preferred to use reagent grade glass, especially since the glass is used to prepare materials which ultimately may be implanted in a human.
  • a melt-derived glass composition can be prepared, for example, by preparing an admixture of the individual metal oxides and other components used to prepare the glass composition, blending the admixture, melting the admixture, and cooling the mixture.
  • the melting temperature is determined in large part by the glass composition, and ranges, for example, from about 900-1500°C, preferably between about 1250 and 1450°C.
  • the melt is preferably mixed, for example, by oxygen bubbling, to ensure a thorough homogenation of the individual components.
  • the mixture can be cooled, for example, by adding the molten admixture to a suitable liquid, such as deionized water, to produce a glass frit.
  • a suitable liquid such as deionized water
  • Porosity can be introduced by grinding the glass into a powder, admixing the powder with a foaming agent, and hot pressing the mixture under vacuum and elevated temperature.
  • the particle size of the glass powder is between about 40 and 70 ⁇ m, the vacuum is preferably less than 50 MPa, and the hot pressing is preferably performed at a temperature above 400°C, preferably between about 400 and 500°C.
  • Suitable foaming agents include compounds which evolve carbon dioxide and/or water at elevated temperatures, for example, metal hydroxides, metal carbonates, and peroxides, such as hydrogen peroxide.
  • Preferred metal carbonates are sodium bicarbonate, sodium carbonate and calcium carbonate.
  • the foaming agents are preferably added in a range of between about 1-5, more preferably 2-3 percent by weight of the glass powder.
  • the preparation of melt-derived porous glass is described, for example, in U.S. Patent No. 5,648,301 to Ducheyne and El Ghannam, the contents of which are hereby incorporated by reference.
  • Glass can be sintered using known methodology.
  • an aqueous slurry of the glass powder and a foaming agent with a suitable binder, such as polyvinyl alcohol, is formed.
  • the slurry is then poured into a mold, allowed to dry, and sintered at high temperatures. These temperature may range, depending on the glass composition and foaming agent used, between about 500 and 1000°C, more preferably between about 600 and 800°C.
  • the glass composition can include a material which can be preferably leached out of the glass composition, and, in doing so, provide the composition with high porosity.
  • a material which can be preferably leached out of the glass composition For example, minute particles of a material capable of being dissolved in a suitable solvent, acid, or base can be mixed with or melted into the glass, and subsequently leached out. The resulting voids have roughly the same size as the particle that was leached out.
  • the size of the pores and degree of porosity depends on the amount of added material relative to the amount of glass.
  • the leached material constituted about 80% of the glass
  • the glass would be approximately 80%> porous when the material was leached out.
  • care should be taken not to leach out those components which add to the bioactivity of the glass, i.e., the calcium and phosphorus oxides.
  • the surface of the glass composition may need to be neutralized to maximize compatibility with the cells to be seeded on the resulting matrix.
  • This can be accomplished, for example, by contacting the glass composition with a suitable buffer for a suitable amount of time to neutralize the surface of the glass (including the surfaces of the voids and pores).
  • Suitable buffers are well known to those of skill in the art, and include TRIS, HEPES, and phosphate buffered saline.
  • the buffer solution is isotonic with the inside of the cells being cultured on the resulting matrix.
  • the glass composition is contacted with cell adhesion peptides, such as RGD, and/or other materials, such as fibronectin, to provide for improved adhesion of the cells to be cultured to the glass composition.
  • cell adhesion peptides such as RGD
  • fibronectin other materials
  • Polymer matrices including the glass composition can be prepared, for example, by melting the polymer, adding the glass composition and any optional components, and cooling the polymer.
  • blowing agents such as carbon dioxide or low boiling organic solvents, such as freon, can be used.
  • components such as salts and sugars which can be readily leached away from most biodegradable polymers, can be added and leached out to provide porosity.
  • care must be taken that the leaching of these materials does not adversely leach out too much of the polymer, particularly when water sensitive polymers such as polyanhydrides are used.
  • Another method for preparing the polymer-glass matrix is to dissolve the polymer in a suitable solvent, add the glass composition and any optional components, and then add a non-solvent for the polymer to cause the polymer to precipitate.
  • a foaming agent for example a gas such as carbon dioxide, will cause the polymer to precipitate as a foam or sponge which includes the glass composition dispersed therein.
  • the composite can be shaped at the same time it is being prepared, for example, by melting the polymer, adding the glass and any optional components, pouring the melt into a suitable mold, and cooling the mixture.
  • the mold include holes which allow the solvent to pass through the mold.
  • the composite can also be shaped as it is formed using three dimensional printing techniques.
  • the polymer include reactive functional groups, such as olefins (preferably in the form of acrylate groups), which can be used to adhere a printed layer to a subsequent printed layer by reacting the groups between the two layers.
  • the composite can be shaped after it is prepared using conventional techniques, such as laser ablation, extrusion, milling, cutting, and computer aided design/computer aided manufacture (CAD/CAM) techniques.
  • conventional techniques such as laser ablation, extrusion, milling, cutting, and computer aided design/computer aided manufacture (CAD/CAM) techniques.
  • the composite matrix can be used as a substrate to promote the growth of tissue, including bone.
  • the matrix is optionally washed with a buffer solution, optionally contacted with cell adhesion peptides or other cell adhesion promoting compounds, and seeded with cells and/or tissue.
  • the matrix is kept in a suitable medium, for example, minimum essential medium, provided with suitable nutrients, and the cells are allowed to grow.
  • the cells and/or tissue can be harvested after the desirable growth is obtained. The harvested cells and/or tissue can be used for implantation, by themselves or while still incorporated in the matrix.
  • the biologically active glass-based substrates are advantageous for use in tissue engineering because collagen fibers have been seen in vitro and in vivo to bond strongly to and be embedded into biologically active glass. This strengthens and promotes the growth of collagen-rich tissues.
  • the composite matrix to grow artificial tissues. For example, if dermal fibroblasts are cultured in a suitable substrate, they lay down collagen and other extracellular matrix proteins to form a dermal layer which may then be implanted onto an injured host site. Chondrocytes cultured in a similar way can produce a cartilage implant material.
  • the matrix When used in vivo, the matrix is optionally washed with a buffer solution, optionally contacted with cell adhesion peptides or other cell adhesion promoting compounds, and implanted to a desired site in a patient. Since the individual components in the matrix are substantially biodegradable and/or biocompatible, the matrix does not need to be removed following implantation.
  • PLA, PGA and copolymers and blends thereof are dissolved in a suitable solvent, e.g., acetone, methylene chloride or chloroform, and precipitated from solution with a non-solvent for the polymer e.g., ethanol, methanol, di ethyl ether, or water.
  • a suitable solvent e.g., acetone, methylene chloride or chloroform
  • a non-solvent for the polymer e.g., ethanol, methanol, di ethyl ether, or water.
  • the remaining solvent and non-solvent are removed, for example, by extraction, evaporation, centrifugation, or other means, to provide a coherent polymeric mass.
  • the mass is subsequently shaped. If there are reactive groups on the polymer, these are then cured.
  • Dry Bioglass® powder is added at various stages during this process, preferably in the range of 10 to 40 volume percent, to yield the desired composite material.
  • Sol-gel Bioglass® is produced as a precipitate from TEOS, phosphorous alkoxide and calcium nitrate in water-ethanol. Continuous fibers are prepared by extruding the sol through a spinneret. The fibers are then aged, dried, and thermally stabilized. Long fibers may be woven into a mesh, short fibers may be combined by mixing them with a degradable adhesive, such as a solution of carboxymethylcellulose (CMC). The resulting material is then heated in a kiln to sinter the material and burn off the binder. The sintered structure may then be impregnated with a bioresorbable (biodegradable) polymer.
  • CMC carboxymethylcellulose
  • Sol-gel derived Bioglass® powder is mixed with a solution of CMC to form a viscous paste. This paste is then allowed to dry, and the CMC polymer is allowed to cross-link. The resulting dry, hardened material is then heated in a kiln to sinter the material. The resulting macroporous structure can then be impregnated, for example by vacuum impregnation methods, with a biodegradable polymer to form a composite substrate.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne des compositions comprenant une composition de verre et un polymère biodégradable, ainsi que des procédés de préparation et d'utilisation de ces compositions pour des cultures de tissu, y compris de tissu osseux. Le verre est composé d'oxydes de silicium, de phosphore, de sodium et de calcium et est dispersé à l'intérieur d'un polymère biodégradable poreux de manière à former une matrice tridimensionnelle. Ces compostions peuvent prendre toutes les formes convenant à l'implantation dans un patient notamment feuilles, vis, stents, broches, sutures, prothèses, valves, plaques etc., ou peuvent se présenter sous une forme convenant à des applications in vitro.
PCT/US1998/016470 1997-08-08 1998-08-07 Substrat bioactif a base de verre WO1999007777A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU88251/98A AU8825198A (en) 1997-08-08 1998-08-07 Biologically active glass-based substrate

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5505997P 1997-08-08 1997-08-08
US60/055,059 1997-08-08

Publications (1)

Publication Number Publication Date
WO1999007777A1 true WO1999007777A1 (fr) 1999-02-18

Family

ID=21995313

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/016470 WO1999007777A1 (fr) 1997-08-08 1998-08-07 Substrat bioactif a base de verre

Country Status (2)

Country Link
AU (1) AU8825198A (fr)
WO (1) WO1999007777A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000015167A1 (fr) 1998-09-10 2000-03-23 Usbiomaterials Corporation Utilisations de compositions contenant du verre bioactif a des fins anti-inflammatoires et antimicrobiennes
WO2001001139A3 (fr) * 1999-06-24 2001-05-03 Univ Mcmaster Introduction et applications d'interactions biomoleculaires dans un support
EP1196150A1 (fr) * 1999-06-14 2002-04-17 Imperial College Innovations Compositions de verre bioactif contenant de l'argent et obtenu par une technique sol-gel
WO2002098474A1 (fr) * 2001-06-05 2002-12-12 Laisheng Biotechnology Inc., Shanghai Produit d'echafaudage dans le domaine du genie tissulaire osseux humain, ses procedes de preparation et ses applications
WO2006027200A1 (fr) * 2004-09-07 2006-03-16 Deep Colours! Gmbh Encre de tatouage
US7118921B1 (en) 1999-06-24 2006-10-10 Mcmaster University Incorporation and applications of biomolecular interactions within a carrier
KR100805303B1 (ko) 2006-10-27 2008-02-20 한국기계연구원 다중적 기공구조를 가지는 다공성 세라믹 재료 및 그제조방법
US7709081B2 (en) * 2004-07-27 2010-05-04 Institut National Des Sciences Appliques (Insa) Porous bioactive glass and preparation method thereof
US7767221B2 (en) 2004-03-05 2010-08-03 The Trustees Of Columbia University In The City Of New York Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone
US8864843B2 (en) 2007-02-12 2014-10-21 The Trustees Of Columbia University In The City Of New York Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement
US11110199B2 (en) 2013-04-12 2021-09-07 The Trustees Of Columbia University In The City Of New York Methods for host cell homing and dental pulp regeneration
CN117771271A (zh) * 2024-02-26 2024-03-29 沈阳市口腔医院 一种快速起效的可视化牙齿脱敏剂及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5525646A (en) * 1991-03-04 1996-06-11 Lundgren; Dan Bioresorbable material and an article of manufacture made of such material for medical use
US5567612A (en) * 1986-11-20 1996-10-22 Massachusetts Institute Of Technology Genitourinary cell-matrix structure for implantation into a human and a method of making
US5744515A (en) * 1995-05-26 1998-04-28 Bsi Corporation Method and implantable article for promoting endothelialization

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5567612A (en) * 1986-11-20 1996-10-22 Massachusetts Institute Of Technology Genitourinary cell-matrix structure for implantation into a human and a method of making
US5525646A (en) * 1991-03-04 1996-06-11 Lundgren; Dan Bioresorbable material and an article of manufacture made of such material for medical use
US5744515A (en) * 1995-05-26 1998-04-28 Bsi Corporation Method and implantable article for promoting endothelialization

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1123072A1 (fr) * 1998-09-10 2001-08-16 Usbiomaterials Corporation Utilisations de compositions contenant du verre bioactif a des fins anti-inflammatoires et antimicrobiennes
EP1123072A4 (fr) * 1998-09-10 2004-09-29 Usbiomaterials Corp Utilisations de compositions contenant du verre bioactif a des fins anti-inflammatoires et antimicrobiennes
WO2000015167A1 (fr) 1998-09-10 2000-03-23 Usbiomaterials Corporation Utilisations de compositions contenant du verre bioactif a des fins anti-inflammatoires et antimicrobiennes
EP1196150A1 (fr) * 1999-06-14 2002-04-17 Imperial College Innovations Compositions de verre bioactif contenant de l'argent et obtenu par une technique sol-gel
EP1196150A4 (fr) * 1999-06-14 2003-01-02 Imp College Innovations Ltd Compositions de verre bioactif contenant de l'argent et obtenu par une technique sol-gel
US7118921B1 (en) 1999-06-24 2006-10-10 Mcmaster University Incorporation and applications of biomolecular interactions within a carrier
WO2001001139A3 (fr) * 1999-06-24 2001-05-03 Univ Mcmaster Introduction et applications d'interactions biomoleculaires dans un support
AU775800B2 (en) * 1999-06-24 2004-08-19 Christopher V. W. Hogue Incorporation and applications of biomolecular interactions within a carrier
WO2002098474A1 (fr) * 2001-06-05 2002-12-12 Laisheng Biotechnology Inc., Shanghai Produit d'echafaudage dans le domaine du genie tissulaire osseux humain, ses procedes de preparation et ses applications
US9427495B2 (en) 2004-03-05 2016-08-30 The Trustees Of Columbia University In The City Of New York Multi-phased, biodegradable and oesteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone
US7767221B2 (en) 2004-03-05 2010-08-03 The Trustees Of Columbia University In The City Of New York Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone
US7709081B2 (en) * 2004-07-27 2010-05-04 Institut National Des Sciences Appliques (Insa) Porous bioactive glass and preparation method thereof
US7510603B2 (en) 2004-09-07 2009-03-31 Ralf Michel Tattooing ink
WO2006027200A1 (fr) * 2004-09-07 2006-03-16 Deep Colours! Gmbh Encre de tatouage
KR100805303B1 (ko) 2006-10-27 2008-02-20 한국기계연구원 다중적 기공구조를 가지는 다공성 세라믹 재료 및 그제조방법
US8864843B2 (en) 2007-02-12 2014-10-21 The Trustees Of Columbia University In The City Of New York Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement
US10265155B2 (en) 2007-02-12 2019-04-23 The Trustees Of Columbia University In The City Of New York Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement
US11110199B2 (en) 2013-04-12 2021-09-07 The Trustees Of Columbia University In The City Of New York Methods for host cell homing and dental pulp regeneration
CN117771271A (zh) * 2024-02-26 2024-03-29 沈阳市口腔医院 一种快速起效的可视化牙齿脱敏剂及其制备方法
CN117771271B (zh) * 2024-02-26 2024-05-03 沈阳市口腔医院 一种快速起效的可视化牙齿脱敏剂及其制备方法

Also Published As

Publication number Publication date
AU8825198A (en) 1999-03-01

Similar Documents

Publication Publication Date Title
Fu et al. Preparation and bioactive characteristics of a porous 13–93 glass, and fabrication into the articulating surface of a proximal tibia
Thavornyutikarn et al. Bone tissue engineering scaffolding: computer-aided scaffolding techniques
Zhang et al. Porous poly (l‐lactic acid)/apatite composites created by biomimetic process
Zhang et al. Calcium phosphate—chitosan composite scaffolds for bone tissue engineering
Zhang et al. Synthetic nano‐fibrillar extracellular matrices with predesigned macroporous architectures
Yang et al. The design of scaffolds for use in tissue engineering. Part I. Traditional factors
US9707079B2 (en) Resorbable macroporous bioactive glass scaffold and method of manufacture
US6328990B1 (en) Bioactive, degradable composite for tissue engineering
CN102423272B (zh) 一种具有网络通道的多孔支架及其制备方法
US5648301A (en) Bioactive material template for in vitro synthesis of bone tissue
US9969971B2 (en) Calcium-containing structures and methods of making and using the same
KR20040010200A (ko) ＣａＯ-ＳｉＯ2계 생체활성 유리 및 그것을 사용하는인산칼슘 유리 소결체
US10149920B2 (en) Implant with controlled porosity made of a hybrid material
WO1999007777A1 (fr) Substrat bioactif a base de verre
Mallick et al. Three‐dimensional porous bioscaffolds for bone tissue regeneration: Fabrication via adaptive foam reticulation and freeze casting techniques, characterization, and cell study
WO2010021559A1 (fr) Pastilles à base d'hydroxyapatite et de bioverre, procédé de production et applications de celles-ci
CN114873921A (zh) 一种含有机聚合物的多孔生物玻璃陶瓷可降解骨创材料及其制备方法
Chanes-Cuevas et al. Macro-, micro-and mesoporous materials for tissue engineering applications.
Chatzistavrou et al. Bioactive glass and glass-ceramic scaffolds for bone tissue engineering
Fiume et al. Robocasting of mesoporous bioactive glasses (MBGs) for bone tissue engineering
Fiume et al. Processing of bioactive glass scaffolds for bone tissue engineering
Nommeots-Nomm et al. Glass and glass-ceramic scaffolds: manufacturing methods and the impact of crystallization on in-vitro dissolution
Jones Bioactive glass as synthetic bone grafts and scaffolds for tissue engineering
CN101116755B (zh) 将细胞粘着强化剂从媒介物均匀涂敷到多孔骨架或管道孔壁表面的方法
Correlo et al. Tissue engineering using natural polymers

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: KR

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载