WO2014168983A1 - Procédé pour favoriser une intégration, une régénération et une étanchéité de tissu autour d'échafaudages - Google Patents

Procédé pour favoriser une intégration, une régénération et une étanchéité de tissu autour d'échafaudages Download PDF

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WO2014168983A1
WO2014168983A1 PCT/US2014/033388 US2014033388W WO2014168983A1 WO 2014168983 A1 WO2014168983 A1 WO 2014168983A1 US 2014033388 W US2014033388 W US 2014033388W WO 2014168983 A1 WO2014168983 A1 WO 2014168983A1
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scaffold
scaffolds
titanium
poly
bone
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PCT/US2014/033388
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English (en)
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Takahiro OWAGA
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The Regents Of The University Of California
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Publication of WO2014168983A1 publication Critical patent/WO2014168983A1/fr

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    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials

Definitions

  • This invention generally relates to a bioactive tissue engineering scaffold and methods of making and using the same.
  • Tissue engineering is the use of cells, proteins (growth factors, cytokines, and other necessary proteins), and scaffolds (framework) to artificially make biological tissues[l].
  • tissue engineering has been expected to produce functional tissues to restore the diseased or injured tissues.
  • the application could expand to the tissue defects after cancer surgery, replacement of nonfunctional or pathological tissues, the reinforcement of damaged or wounded tissue, and the augmentation of tissues for better structural integrity and function.
  • the tissues of targeting would range from soft tissues, such as various organs, blood vessels, skin, and mucosa, to hard tissues, such as bone, cartilage, and teeth.
  • tissue engineering technology is often used as a synonym of tissue engineering. Basic concept of regenerative medicine is that using engineered tissue or using scaffolds to deliver cells and proteins, the damaged or diseased tissues would be regenerated or restored.
  • the thicker the better the scaffold to reproduce tissues with suitable size, mechanical integrity and sustainability, and space/shape maintaining ability, and tolerance for biological and physiological function[12-15].
  • the crucial challenge is that cells and proteins do not reach the inside of such thick scaffold, resulting in the void or incompleteness of tissue regeneration. Not only tissue regeneration, but also vascularization, which is important to remodel and maintain the tissues, does not take place within the thick scaffold[16]. If scaffolds are made of resorbable materials, such as various polymers, tissue may grow inside but the mechanical and structural requirements are not met or severely compromised.
  • the titanium scaffolds were ultra-violet light treated (a combination of UVA and UVC) and characterized with electropositiveness, hydrophilic, reduced surface carbon percentage, and a 100% water and oleo-infiltration.
  • a three-dimensional scaffold for tissue engineering comprising metallic fibers, thin film, membrane, or a combination thereof, wherein the scaffold is characterized with electropositiveness, hydrophilicity, reduced surface carbon percentage, and a complete or substantially complete water infiltration so as to cause cells and proteins to reach the inside of the scaffold to engineer a 3 -dimensional, functional, structurally suitable, and mechanically tolerant and sustainable tissue.
  • the metallic fiber has a diameter between about 800 nm to about 1 mm. In some embodiments of the scaffold of invention, the metallic thin film or membrane has a thickness between about 800 nm to about 1 mm.
  • the electropositiveness is characterized by an electric charge ranging from 0.001 nC to about 5.00 nC.
  • the metallic fiber, thin film, or membrane comprises titanium.
  • the metallic fiber, thin film, or membrane comprises a metal selected from gold, platinum, tantalum, niobium, nickel, iron, chromium, titanium, titanium alloy, titanium oxide, cobalt, zirconium, zirconium oxide, manganese, magnesium, aluminum, palladium, an alloy formed thereof, or combinations thereof.
  • the scaffold is treated by ultraviolet light (UV) for a period of time of sufficient length so as to generate the electropositiveness.
  • UV ultraviolet light
  • the scaffold is jaw bone scaffold, repairing and stabilizing screws, pins, frames, and plates for bone, spinal scaffolds, femoral scaffolds, neck scaffolds, knee scaffolds, wrist scaffolds, joint scaffolds, maxillofacial prosthetic, limb prostheses for conditions resulting from injury and disease, and combinations thereof.
  • the scaffold comprises a polymeric material or a bone cement material.
  • the UV light has an intensity of about 0.05 mW/cm to about 4.0 mW/cm of a wave length from about 400 nm to about 100 nm.
  • a three-dimensional scaffold comprising metallic fiber, thin film, membrane, or a combination thereof; treating the scaffold with ultraviolet light (UV) for a period of time of sufficient length so as to generate a scaffold characterized with electropositiveness, hydrophilicity, reduced surface carbon percentage, and a complete or substantially complete water infiltration so as to cause cells and proteins to reach the inside of the scaffold to engineer a 3 -dimensional, functional, structurally suitable, and mechanically tolerant and sustainable tissue.
  • UV ultraviolet light
  • the metallic fiber has a diameter between about 800 nm to about 1 mm.
  • the metallic thin film or membrane has a thickness between about 800 nm to about 1 mm.
  • the electropositiveness is characterized by an electric charge ranging from 0.001 nC to about 5.00 nC.
  • the metallic fiber, thin film, or membrane comprises titanium.
  • metallic fiber, thin film, or membrane comprises a metal selected from gold, platinum, tantalum, niobium, nickel, iron, chromium, titanium, titanium alloy, titanium oxide, cobalt, zirconium, zirconium oxide, manganese, magnesium, aluminum, palladium, an alloy formed thereof, or combinations thereof.
  • the scaffold is treated by ultraviolet light (UV) for a period of time of sufficient length so as to generate the electropositiveness.
  • UV ultraviolet light
  • the scaffold is selected from the group consisting of jaw bone scaffold, repairing and stabilizing screws, pins, frames, and plates for bone, spinal scaffolds, femoral scaffolds, neck scaffolds, knee scaffolds, wrist scaffolds, joint scaffolds, maxillofacial prosthetic, limb prostheses for conditions resulting from injury and disease, and combinations thereof.
  • the scaffold comprises a polymeric material or a bone cement material.
  • the UV light has an intensity of about
  • the period of time is about between 1 and 20 minutes or longer.
  • a method for tissue engineering comprising applying to a subject a three-dimentional scaffold of the various embodiments disclosed above or below to engineer a tissue.
  • Soft tissues including but not limited to heart, lung, liver, bladder, saliva glands, kidney, prostates, skin, mucosa, blood vessels, ligaments, cartilage, and hard tissues, including but not limited to bone and teeth.
  • Figure 1 illustrates an exemplary embodiment, showing the surface of titanium scaffolds was converted from hydrophobic (a contact angle > 60 degree) to superhydrophilic (a contact angle of less than 10 degree) after UV treatment.
  • Figure 2 illustrates an exemplary embodiment, showing that the wet area (the area of water infiltration) on untreated scaffolds was limited to the external area facing the surrounding water (by images analysis, only a 0.1-5% of the whole scaffold area was wet) while the entire area of UV-treated scaffolds was immersed in water and the water infiltration was 100%.
  • Figure 3 illustrates an exemplary embodiment, showing that very similarly to water dynamics, the wettable area on untreated scaffolds was limited to the external area facing the surrounding glycerol (images analysis showed only a 0.1-5% of the whole scaffold area was wettable to glycerol) while the entire area of UV-treated scaffolds was immersed in glycerol and the oleo-infiltration was 100%.
  • Figure 4 illustrates an exemplary embodiment, showing when the scaffold was placed into a hole drilled in the rat femur, the untreated scaffold did not absorb blood, and in contrast, blood immediately infiltrated into UV-treated scaffolds.
  • Figure 5 illustrates an exemplary embodiment, showing that amount of osteoblasts attached to scaffolds during a certain period time were considerably increased when the scaffolds were treated with UV (p ⁇ 0.01).
  • Figure 6 illustrates an exemplary embodiment, showing that amount of salivary gland cells attached to scaffolds during a certain period time were considerably increased when the scaffolds were treated with UV (p ⁇ 0.01).
  • Figure 7 illustrates an exemplary embodiment, showing that skin fibroblasts attached to scaffolds during a certain period time were considerably increased when the scaffolds were treated with UV (p ⁇ 0.01).
  • Figure 8 illustrates an exemplary embodiment, showing that a UV-treated scaffold was placed in the rat femur with its top 2 mm (red outline) located outside the native bone (green outline); in this 2 mm zone, immediate blood infiltration was confirmed during surgery, and at week 3 post-operation, bone tissue was formed in the 2mm zone.
  • the titanium scaffolds were ultra-violet light treated (a combination of UVA and UVC) and characterized with electropositiveness, hydrophilic, reduced surface carbon percentage, and a 100% water and oleo-infiltration.
  • a three-dimensional scaffold for tissue engineering comprising metallic fibers, thin film, membrane, or a combination thereof, wherein the scaffold is characterized with electropositiveness, hydrophilicity, reduced surface carbon percentage, and a complete or substantially complete water infiltration so as to cause cells and proteins to reach the inside of the scaffold to engineer a 3 -dimensional, functional, structurally suitable, and mechanically tolerant and sustainable tissue.
  • the metallic fiber has a diameter between about 800 nm to about 1 mm. In some embodiments of the scaffold of invention, the metallic thin film or membrane has a thickness between about 800 nm to about 1 mm.
  • the electropositiveness is characterized by an electric charge ranging from 0.001 nC to about 5.00 nC.
  • the metallic fiber, thin film, or membrane comprises titanium.
  • the metallic fiber, thin film, or membrane comprises a metal selected from gold, platinum, tantalum, niobium, nickel, iron, chromium, titanium, titanium alloy, titanium oxide, cobalt, zirconium, zirconium oxide, manganese, magnesium, aluminum, palladium, an alloy formed thereof, or combinations thereof.
  • the scaffold is treated by ultraviolet light (UV) for a period of time of sufficient length so as to generate the electropositiveness.
  • UV ultraviolet light
  • the scaffold is jaw bone scaffold, repairing and stabilizing screws, pins, frames, and plates for bone, spinal scaffolds, femoral scaffolds, neck scaffolds, knee scaffolds, wrist scaffolds, joint scaffolds, maxillofacial prosthetic, limb prostheses for conditions resulting from injury and disease, and combinations thereof.
  • the scaffold comprises a polymeric material or a bone cement material.
  • the UV light has an intensity of about 0.05 mW/cm to about 4.0 mW/cm of a wave length from about 400 nm to about 100 nm.
  • a three-dimensional scaffold comprising metallic fiber, thin film, membrane, or a combination thereof; treating the scaffold with ultraviolet light (UV) for a period of time of sufficient length so as to generate a scaffold characterized with electropositiveness, hydrophilicity, reduced surface carbon percentage, and a complete or substantially complete water infiltration so as to cause cells and proteins to reach the inside of the scaffold to engineer a 3 -dimensional, functional, structurally suitable, and mechanically tolerant and sustainable tissue.
  • UV ultraviolet light
  • the metallic fiber has a diameter between about 800 nm to about 1 mm.
  • the metallic thin film or membrane has a thickness between about 800 nm to about 1 mm.
  • the electropositiveness is characterized by an electric charge ranging from 0.001 nC to about 5.00 nC.
  • the metallic fiber, thin film, or membrane comprises titanium.
  • metallic fiber, thin film, or membrane comprises a metal selected from gold, platinum, tantalum, niobium, nickel, iron, chromium, titanium, titanium alloy, titanium oxide, cobalt, zirconium, zirconium oxide, manganese, magnesium, aluminum, palladium, an alloy formed thereof, or combinations thereof.
  • the scaffold is treated by ultraviolet light (UV) for a period of time of sufficient length so as to generate the electropositiveness.
  • UV ultraviolet light
  • the scaffold is selected from the group consisting of jaw bone scaffold, repairing and stabilizing screws, pins, frames, and plates for bone, spinal scaffolds, femoral scaffolds, neck scaffolds, knee scaffolds, wrist scaffolds, joint scaffolds, maxillofacial prosthetic, limb prostheses for conditions resulting from injury and disease, and combinations thereof.
  • the scaffold comprises a polymeric material or a bone cement material.
  • the period of time is about between 1 and 20 minutes or longer.
  • a method for tissue engineering comprising applying to a subject a three-dimentional scaffold of the various embodiments disclosed above or below to engineer a tissue.
  • Soft tissues including but not limited to heart, lung, liver, bladder, saliva glands, kidney, prostates, skin, mucosa, blood vessels, ligaments, cartilage, and hard tissues, including but not limited to bone and teeth.
  • stronger (higher intensity) or weaker (lower intensity) UV light can be used.
  • stronger (higher intensity) or weaker (lower intensity) UV light can be used.
  • the UV light is of an intensity of about 0.05 mW/cm 2
  • the period of time is about between 1 and 20 minutes or longer.
  • a method for tissue engineering comprising applying to a subject a three-dimentional scaffold of the various embodiments disclosed above or below to engineer a tissue.
  • Soft tissues including but not limited to heart, lung, liver, bladder, saliva glands, kidney, prostates, skin, mucosa, blood vessels, ligaments, cartilage, and hard tissues, including but not limited to bone and teeth.
  • the period of time is about 20 minutes or longer.
  • the time of UV treatment is conversely related to the UV intensity. Generally speaking, treatment of the scaffold disclosed herein using UV having an higher intensity would require a shorter time of UV treatment, and vice versa.
  • the electrostatic properties comprise positive charges ranging from 0.001 nC to 10.00 nC (e.g., 0.001 nC to 5.00 nC).
  • the scaffold comprises a metallic material such as metallic fibers, or foldable metals such as film or membrane, which are defined above.
  • the scaffold comprises gold, platinum, tantalum, niobium, nickel, iron, chromium, titanium, titanium alloy, titanium oxide, cobalt, zirconium, zirconium oxide, manganese, magnesium, aluminum, palladium, an alloy formed thereof, or combinations thereof.
  • the scaffold is selected from the group consisting of tooth scaffolds, jaw bone scaffold, repairing and stabilizing screws, pins, frames, and plates for bone, spinal scaffolds, femoral scaffolds, neck scaffolds, knee scaffolds, wrist scaffolds, joint scaffolds, maxillofacial prosthetic, limb prostheses for conditions resulting from injury and disease, and combinations thereof.
  • the scaffold comprises a polymeric material or a bone cement material.
  • the bone cement material comprises a material selected from the group consisting of polyacrylates, polyesters, poly(methyl methacrylate) (PMMA) or methyl methacrylate (MMA), bioglass, ceramics, calcium-based materials, calcium phosphate-based materials, and combinations thereof.
  • a method of treating a medical condition in a subject comprising implanting in the subject a scaffold in need thereof, wherein the scaffold is as the various embodiments of invention scaffold disclosed above or below.
  • the medical condition is a dental condition.
  • the medical condition is a bone-related condition.
  • UV light is electromagnetic radiation with
  • UV lights can be divided into UVA (400 nm to 315 nm), UVB (315 nm to 280 nm), and UVC (280 nm to 100 nm). Different wave length of UV, such as UVA, UVB, and UVC, imparts properties to UV lights that can be very different. For example, UVC is germicidal while UVA may be less effective as germicide.
  • UV or "UV light” shall not encompass a UV laser or UV laser beam. Such UV light does not encompass any UV beam obtained through optical amplification such as those fall within the definition of laser as described in Gould, R. Gordon (1959). "The LASER, Light Amplification by Stimulated Emission of Radiation”. In Franken, P.A. and Sands, R.H. (Eds.). The Ann Arbor Conference on Optical Pumping, the University of Michigan, 15 June through 18 June 1959. p. 128.
  • carbon content refers to any contamination in air
  • tissue integration capability refers to the ability of a scaffold to be integrated into the tissue of a biological body.
  • the tissue integration capability of a scaffold can be generally measured by several factors, one of which is wettability of the scaffold surface, which reflects the hydrophilicity/oleophilicty
  • Hydrophilicity or hemophilicity of a scaffold surface. Hydrophilicity and oleophilicity are relative terms and can be measured by, e.g., water contact angle (Oshida Y, et al., J Mater Science 3:306-312 (1992)), and area of water spread (Gifu-kosen on line text,
  • the hydrophilicity/oleophilicity can be measured by contact angle or area of water spread of a scaffold surface described herein relative to the ones of the control scaffold surfaces. Relative to the scaffold surfaces not treated with the process described herein, a scaffold treated with the process described herein has a substantially lower contact angle or a substantially higher area of water spread.
  • electrostatic properties shall mean electric charge on the surface. Such electric charge can be positive or negative.
  • positive charges can be, for example, charges on a metal atom or metal oxide, for example, Ti(+), Ti(+2), Ti(+3), or Ti(+4) or TiO(+l) or TiO(+2), etc.
  • such electrostatic properties can be positive charges having a monovalent positivity, which is demonstrated by the fact they can be neutralized by adding monovalent anions.
  • such electrostatic properties can be positive charges ranging from 0.001 nC 10.00 nC, e.g., 0.001 nC to 5.00 nC.
  • the scaffold refers to a framework that supports tissue regeneration.
  • a framework is generally not a solid structure and allows cells to grow inside and outside the framework so as to achieve tissue regeneration.
  • the scaffold as used herein excludes a medical implant having a solid or substantially solid structure.
  • a scaffold described herein can comprise metal fibers and/or any other foldable of metal, such as film/membrane.
  • the scaffold can further include a polymer material and/or a bone cement material.
  • the scaffolds described herein with enhanced tissue integration capabilities include any scaffolds currently available in medicine or to be introduced in the future.
  • the scaffolds can be metallic or non-metallic scaffolds.
  • Non-metallic scaffolds include, for example, ceramic scaffolds, calcium phosphate or polymeric scaffolds.
  • Useful polymeric scaffolds can be any biocompatible scaffolds, e.g., bio-degradable polymeric scaffolds.
  • Ceramic scaffolds include, e.g., bioglass and silicon dioxide scaffolds.
  • Calcium phosphate scaffolds includes, e.g., hydroxyapatite, tricalcium phosphate (TCP).
  • Exemplary polymeric scaffolds include, e.g., poly-lactic-co-glycolic acid (PLGA), polyacrylate such as polymethacrylates and polyacrylates, and poly-lactic acid (PLA) scaffolds.
  • PLGA poly-lactic-co-glycolic acid
  • PLA polyacrylate
  • the scaffold described herein can specifically exclude any of the
  • the scaffold comprises a metallic material or a bone-cement material.
  • the bone cement material can be any bone cement material known in the art.
  • Some representative bone cement materials include, but are not limited to, polyacrylate or polymethacrylate based materials such as poly(methyl methacrylate) (PMMA)/methyl methacrylate (MMA), polyester based materials such as PLA or PLGA, bioglass, ceramics, calcium phosphate-based materials, calcium-based materials, and combinations thereof.
  • the scaffold can include any polymer described below. In some embodiments, the scaffold described herein can specifically exclude any of the
  • Titanium scaffolds include tooth or bone replacements made of titanium or an alloy that includes titanium. Titanium bone replacements include, e.g., knee joint and hip joint prostheses, femoral neck replacement, spine replacement and repair, neck bone replacement and repair, jaw bone repair, fixation and augmentation, transplanted bone fixation, and other limb prostheses.
  • None -titanium metallic scaffolds include tooth or bone scaffolds made of gold, platinum, tantalum, niobium, nickel, iron, chromium, titanium, titanium alloy, titanium oxide, cobalt, zirconium, zirconium oxide, manganese, magnesium, aluminum, palladium, an alloy formed thereof, e.g., stainless steel, or combinations thereof.
  • alloys are titanium-nickel allows such as nitanol, chromium-cobalt alloys, stainless steel, or combinations thereof.
  • the metallic scaffold can specifically exclude any of the aforementioned metals.
  • the scaffold described herein can be porous or non-porous scaffolds. Porous scaffolds can impart better tissue integration while non-porous scaffolds can impart better mechanical strength.
  • the scaffolds can be metallic scaffolds or non-metallic scaffolds.
  • the scaffolds are metallic scaffolds such as titanium scaffolds, e.g., titanium scaffolds for replacing missing teeth (dental scaffolds) or fixing diseased, fractured or transplanted bone.
  • Other exemplary metallic scaffolds include, but are not limited to, titanium alloy scaffolds, chromium-cobalt alloy scaffolds, platinum and platinum alloy scaffolds, nickel and nickel alloy scaffolds, stainless steel scaffolds, zirconium,
  • chromium-cobalt alloy gold or gold alloy scaffolds, and aluminum or aluminum alloy scaffolds.
  • the scaffolds provided herein can be subjected to various established surface treatments to increase surface area or surface roughness for better tissue integration or tissue attachment.
  • Representative surface treatments include, but are not limited to, physical treatments and chemical treatments.
  • Physical treatments include, e.g., machined process, sandblasting process, metallic deposition, non-metallic deposition (e.g., apatite deposition), or combinations thereof.
  • Chemical treatment includes, e.g., etching using a chemical agent such as an acid, base (e.g., alkaline treatment), oxidation (e.g., heating oxidation and anodic oxidation), and combinations thereof.
  • a metallic scaffold can form different surface topographies by a machined process or an acid-etching process.
  • the polymers can be any polymer commonly used in the medical device industry.
  • the polymers can be biocompatible or non-biocompatible.
  • the polymer can be poly(ester amide), polyhydroxyalkanoates (PHA), poly(3-hydroxyalkanoates) such as poly(3-hydroxypropanoate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate),
  • polycyanoacrylates poly(trimethylene carbonate), poly(iminocarbonate), polyphosphazenes, silicones, polyesters, polyolefms, polyisobutylene and ethylene-alphaolefm copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, such as polyvinyl chloride, polyvinyl ethers, such as polyvinyl methyl ether, polyvinylidene halides, such as polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, such as polystyrene, polyvinyl esters, such as polyvinyl acetate, copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers, polyamides, such as
  • polyalkylene oxides such as poly(ethylene oxide), poly(propylene oxide), poly(ether ester), polyalkylene oxalates, phosphoryl choline containing polymer, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as 2-hydroxyethyl
  • HEMA hydroxypropyl methacrylate
  • HPMA hydroxypropyl methacrylate
  • PEGA PEG acrylate
  • MPC 2-methacryloyloxyethylphosphorylcholine
  • VP n-vinyl pyrrolidone
  • carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA),
  • poly(styrene-isoprene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene-PEG, polycaprolactone-PEG (PCL-PEG), PLA-PEG, poly(methyl methacrylate)-PEG
  • PMMA-PEG polydimethylsiloxane-co-PEG
  • PVDF-PEG poly(vinylidene fluoride)-PEG
  • PLURONICTM surfactants polypropylene oxide-co-polyethylene glycol
  • poly(tetramethylene glycol) poly(tetramethylene glycol)
  • hydroxy functional poly( vinyl pyrrolidone) molecules such as collagen, chitosan, alginate, fibrin, fibrinogen, cellulose, starch, dextran, dextrin, hyaluronic acid, fragments and derivatives of hyaluronic acid, heparin, fragments and derivatives of heparin, glycosamino glycan (GAG), GAG derivatives, polysaccharide, elastin, elastin protein mimetics, or combinations thereof.
  • elastin protein mimetics include (LGGVG) n , (VPGVG) n , Val-Pro-Gly-Val
  • the polymer can be poly(ethylene-co-vinyl alcohol) , poly(methoxyethyl methacrylate), poly(dihydroxylpropyl methacrylate), polymethacrylamide, aliphatic polyurethane, aromatic polyurethane, nitrocellulose, poly(ester amide benzyl), co-poly- ⁇ [N,N'-sebacoyl-bis-(L-leucine)-l,6-hexylene diester]o.75-[N,N'-sebacoyl-L-lysine benzyl ester]o.2s ⁇ (PEA-Bz), co-poly- ⁇ [N,N'-sebacoyl-bis-(L-leucine)-l,6-hexylene diester] 0 .75-[N,N'-sebacoyl-L-lysine-4-amino-TEMPO amide] 0 . 2 5 ⁇ (PEA-Bz),
  • polytetrafluoroethylene a biopolymer such as elastin mimetic protein polymer, star or hyper-branched SIBS (styrene-block-isobutylene-block-styrene), or combinations thereof.
  • SIBS styrene-block-isobutylene-block-styrene
  • the polymer can be a block copolymer that can be, e.g., di-, tri-, terra-, or oligo-block copolymers or a random copolymer.
  • the polymer can also be branched polymers such as star polymers.
  • a UV-transmitting material having the features described herein can exclude any one of the aforementioned polymers.
  • poly(D,L-lactide-co-glycolide), and poly(L-lactide-co-glycolide) can be used interchangeably with the terms poly(D,L-lactic acid), poly(L-lactic acid), poly(D,L-lactic acid-co-glycolic acid), or poly(L-lactic acid-co-glycolic acid), respectively.
  • the scaffolds provided herein can be used for treating, preventing, ameliorating, correcting, or reducing the symptoms of a medical condition by implanting the scaffolds in a mammalian subject.
  • the mammalian subject can be a human being or a veterinary animal such as a dog, a cat, a horse, a cow, a bull, or a monkey.
  • Representative medical conditions that can be treated or prevented using the scaffolds provided herein include, but are not limited to, missing teeth or bone related medical conditions such as femoral neck fracture, missing teeth, a need for orthodontic anchorage or bone related medical conditions such as femoral neck fracture, neck bone fracture, wrist fracture, spine fracture/disorder or spinal disk displacement, fracture or degenerative changes of joints such as knee joint arthritis, bone and other tissue defect or recession caused by a disorder or body condition such as, e.g., cancer, injury, systemic metabolism, infection or aging, and combinations thereof.
  • a disorder or body condition such as, e.g., cancer, injury, systemic metabolism, infection or aging, and combinations thereof.
  • the scaffolds provided herein can be used to treat, prevent, ameliorate, or reduce symptoms of a medical condition such as missing teeth, a need for orthodontic anchorage or bone related medical conditions such as femoral neck fracture, neck bone fracture, wrist fracture, spine fracture/disorder or spinal disk displacement, fracture or degenerative changes of joints such as knee joint arthritis, bone and other tissue defect or recession caused by a body condition or disorder such as cancer, injury, systemic metabolism, infection and aging, limb amputation resulting from injuries and diseases, and combinations thereof.
  • a medical condition such as missing teeth
  • a need for orthodontic anchorage or bone related medical conditions such as femoral neck fracture, neck bone fracture, wrist fracture, spine fracture/disorder or spinal disk displacement, fracture or degenerative changes of joints such as knee joint arthritis, bone and other tissue defect or recession caused by a body condition or disorder such as cancer, injury, systemic metabolism, infection and aging, limb amputation resulting from injuries and diseases, and combinations thereof.
  • titanium scaffolds with remarkably increased water- and oleo-infiltration capability, resulting in a considerable increase in cell recruitment, attachment, and tissue formation. It is known that cells to make soft and hard tissues act differently but these scaffolds are proven effective to both cell types.
  • the titanium scaffolds were ultra-violet light treated (a combination of UVA and UVC) and characterized with electropositiveness, hydrophilic, reduced surface carbon percentage, and a 100% water and oleo-infiltration. Materials and methods
  • the chemical composition of scaffold surfaces was evaluated by electron spectroscopy for chemical analysis (ESCA).
  • ESCA was performed by X-ray photoelectron spectroscopy (XPS) under high vacuum conditions (6 x 10 ⁇ 7 Pa).
  • Hydrophilicity of the scaffold with and without UV treatment was evaluated by wettability to water as the contact angle of 3 ⁇ of ddH 2 0.
  • Electrostatic status of scaffolds before and after UV treatment was examined by a coulomb meter.
  • the degree of water infiltration into a scaffold was evaluated by image analysis.
  • the area of water infiltration into the scaffold was evaluated on a photo image of a scaffold immersed in water for 1 h.
  • the percentage of wet area was calculated relative the whole area of the scaffold.
  • lipid infiltration into scaffold is critical to evaluate tissue engineering scaffolds for their ability to attract and recruit biological cells.
  • the degree of glycerol infiltration into a scaffold was evaluated by image analysis as mentioned above.
  • EDTA-4Na and seeded onto the scaffolds at a density of 4x 10 cells/cm .
  • salivary gland cells and skin fibroblasts were extracted from submandibular salivary glands and dorsal skin, respectively, of 8-week-old male Sprague-Dawley rats.
  • the attachment of cells was evaluated by measuring the amount of cells attached to titanium disks after 6 and 24 h of incubation using WST-1 based colorimetry (WST-1, Roche Applied Science, Mannheim, Germany).
  • WST-1 based colorimetry
  • the culture well was incubated with 100 ⁇ tetrazolium salt (WST-1) reagent at 37°C for 4 h.
  • the amount of formazan produced was measured using an ELIS A reader at 420 nm.
  • the surface of titanium scaffolds was converted from hydrophobic (a contact angle >
  • the wet area (the area of water infiltration) on untreated scaffolds was limited to the external area facing the surrounding water. Images analysis indicated only a 0.1-5% of the whole scaffold area was wet. In contrast, apparently enough, the entire area of UV-treated scaffolds was immersed in water and the water infiltration was 100%. Oleo-infiltration Because biological cells are made of lipid, the ability of scaffolds to absorb lipid is very important to evaluate their tissue regeneration potential. As shown in Figure 3, very similarly to water dynamics, the wettable area on untreated scaffolds was limited to the external area facing the surrounding glycerol. Images analysis indicated only a 0.1-5% of the whole scaffold area was wettable to glycerol. In contrast, obviously enough, the entire area of UV-treated scaffolds was immersed in glycerol and the oleo-infiltration was 100%.
  • a UV-treated scaffold was placed in the rat femur with its top 2 mm (red outline) located outside the native bone (green outline).
  • 2 mm red outline
  • native bone green outline
  • immediate blood infiltration was confirmed during surgery, and at week 3 post-operation, bone tissue was formed in the 2mm zone.
  • the finding was a confirmation of 2 mm significant

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Abstract

L'invention concerne des procédés qui permettent de favoriser une intégration de tissu avec des échafaudages, et une génération, une régénération et une étanchéité de tissu autour d'échafaudages.
PCT/US2014/033388 2013-04-08 2014-04-08 Procédé pour favoriser une intégration, une régénération et une étanchéité de tissu autour d'échafaudages WO2014168983A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050100578A1 (en) * 2003-11-06 2005-05-12 Schmid Steven R. Bone and tissue scaffolding and method for producing same
US20080145934A1 (en) * 2004-09-28 2008-06-19 Ian Ross Harris Tissue-engineering scaffolds containing self-assembled-peptide hydrogels
US20100303880A1 (en) * 2005-04-28 2010-12-02 Reddy Harry K Tissue scaffolding comprising surface folds for tissue engineering
US20110313536A1 (en) * 2008-11-25 2011-12-22 The Regents Of The University Of California Functionalized titanium implants and related regenerative materials
US20120128739A1 (en) * 2009-06-26 2012-05-24 Region Midtjylland Three-dimensional nanostructured hybrid scaffold and manufacture thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050100578A1 (en) * 2003-11-06 2005-05-12 Schmid Steven R. Bone and tissue scaffolding and method for producing same
US20080145934A1 (en) * 2004-09-28 2008-06-19 Ian Ross Harris Tissue-engineering scaffolds containing self-assembled-peptide hydrogels
US20100303880A1 (en) * 2005-04-28 2010-12-02 Reddy Harry K Tissue scaffolding comprising surface folds for tissue engineering
US20110313536A1 (en) * 2008-11-25 2011-12-22 The Regents Of The University Of California Functionalized titanium implants and related regenerative materials
US20120128739A1 (en) * 2009-06-26 2012-05-24 Region Midtjylland Three-dimensional nanostructured hybrid scaffold and manufacture thereof

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