WO2008130068A1 - Procede de preparation d'un echafaudage polymere poreux a partir de glace seche - Google Patents

Procede de preparation d'un echafaudage polymere poreux a partir de glace seche Download PDF

Info

Publication number
WO2008130068A1
WO2008130068A1 PCT/KR2007/001972 KR2007001972W WO2008130068A1 WO 2008130068 A1 WO2008130068 A1 WO 2008130068A1 KR 2007001972 W KR2007001972 W KR 2007001972W WO 2008130068 A1 WO2008130068 A1 WO 2008130068A1
Authority
WO
WIPO (PCT)
Prior art keywords
scaffold
porous
polymer
slush
porous polymer
Prior art date
Application number
PCT/KR2007/001972
Other languages
English (en)
Inventor
So Hee Yun
Hyun Sook Park
Song Sun Chang
Original Assignee
Modern Cell & Tissue Technologies Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Modern Cell & Tissue Technologies Inc. filed Critical Modern Cell & Tissue Technologies Inc.
Priority to PCT/KR2007/001972 priority Critical patent/WO2008130068A1/fr
Publication of WO2008130068A1 publication Critical patent/WO2008130068A1/fr

Links

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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/425—Porous materials, e.g. foams or sponges

Definitions

  • the present invention relates to a method of preparing a porous polymer scaffold, which enables the size and shape of pores, which are formed in the preparation of the porous scaffold using a freeze drying method, to be uniform throughout the three-dimensional structure of the porous scaffold. More specifically, the present invention relates to a method for preparing a porous polymer scaffold which can be used as a scaffold for three-dimensional cell culture, a tissue engineering scaffold or a wound dressing, the method being characterized in that it comprises, in addition to the steps of the prior freeze-drying method, a step of mixing a polymer solution with dry ice to form a slush-like material.
  • tissue engineering a field of biotechnology
  • tissue engineering a field of biotechnology
  • tissue engineering a new approach, defined as such tissue engineering
  • Tissue engineering is an applied study that utilizes the basic concepts and techniques of life science and engineering to understand the relationship between the structure and function of biological tissue and make a biological tissue substitute for transplantation, thereby to maintain, improve or restore the function of the human body.
  • An ideal polymer scaffold for use for this purpose should be made of a nontoxic, biocompatible material, which does not cause blood coagulation or inflammatory reaction after transplantation, and should have mechanical properties which can sufficiently support the growth of cells. Also, it should be in the form of a porous scaffold to which cells readily adhere and in which a sufficient space between cells is ensured such that oxygen or nutrients are easily supplied through the diffusion of body fluids, and angiogenesis readily occurs such that cells successfully grow and differentiate.
  • cells are basically cultured in a two-dimensional environment, but three-dimensional scaffolds are required to culture the cells in the form of tissues or organs.
  • Such scaffolds have innumerable pores, and thus they should be able to attach cells to the inside and outside thereof and should have an opened structure in order to receive nutrients required for the growth of cells and to discharge waste matter.
  • Typical methods for preparing such three-dimensional porous polymer scaffolds include: a solvent-casting and particle-leaching technique comprising mixing a polymer with single-crystal salt particles, drying the mixture and then immersing the dried material to leach the salt particles (A. G. Mikos et al., Polymer, 35, 1068 (1994)); a gas forming technique comprising expanding a polymer with CO 2 gas (L. D. Harris et al., J. Biomed. Mater. Res., 42, 396 (1998)); a thermally induced phase separation technique including immersing a polymer-containing solvent in a non-solvent to make the polymer porous (C. Schugens, et al., J. Biomed. Mater.
  • the solvent-casting and particle-leaching technique uses a large amount of salt particles and adopts a method of controlling pores by controlling the size of the salt particles, but has a disadvantage in that the salt particles can adversely affect cells when the subsequent complete removal thereof is not achieved. Also, the gas forming technique has a problem in that the uniformity of structures can be reduced because it is difficult to control pores. Moreover, in the freeze-drying method, which is one of the most widely used methods, when the polymer solution is cooled, the phase separation between the solvent and the solute will occur due to the difference in solubility therebetween, while the solvent will form crystals, so that the solute will make a scaffold, and the solvent will forms pores. Thus, it is possible to control pores depending on the concentration and cooling temperature of the polymer solution. However, during the cooling of the polymer solution, a temperature gradient can be formed between the surface and inside of the solution, resulting in different pore shapes. Thus, a porous scaffold having non-uniform and closed pores can be prepared.
  • a porous polymer scaffold having uniform pores throughout the three-dimensional structure thereof can be prepared by mixing a polymer solution with dry ice to make a slush-like material, cooling the slush-like material such that the surface and inside of the slush-like material are rapidly cooled at the same temperature and cooling rate, and then dry-freezing the cooled material, thereby completing the present invention.
  • Another object of the present invention is to provide a porous scaffold prepared according to said method, as well as a cell culture scaffold, a tissue engineering scaffold or a wound dressing, which comprise said porous scaffold.
  • a method for preparing a porous polymer scaffold comprising the steps of: a) dissolving a polymer in a solvent; b) adding dry ice to the polymer solution; c) stirring the mixture to form a slush-like material; and d) placing the slush-like material in a mold, followed by freeze drying.
  • the present invention improves the prior method of preparing a porous polymer scaffold using the freeze-drying method. Specifically, in the prior method of preparing a porous polymer scaffold using the freeze-drying method, a temperature gradient is formed between the surface and inside of a polymer solution according to the transfer direction of cold air, and thus a porous scaffold, having different pore shapes and nonuniform and closed pores, can be prepared (see FIG. 1).
  • a porous polymer scaffold having uniform pores throughout the three-dimensional structure thereof can be prepared by mixing a polymer solution with dry ice to make a slush-like material, cooling the slush-like material such that the surface and inside of the slush-like material are rapidly cooled at the same temperature and cooling rate, and then dry-freezing the cooled material.
  • any artificial/natural biodegradable, or non-degradable polymer may be used as long as it can be dissolved in a solvent and prepared into a porous scaffold by freeze drying.
  • the polymer in the step a) is either a synthetic biodegradable polymer selected from the group consisting of poly glycolic acid (PGA), poly lactic acid (PLA), and poly(DL-lactic- co-glycolic acid) (PLGA), or a natural biodegradable polymer selected from the group consisting of chitosan, collagen and inorganic hydroxyapatite, a copolymer thereof, or a mixture thereof.
  • PGA poly glycolic acid
  • PLA poly lactic acid
  • PLGA poly(DL-lactic- co-glycolic acid)
  • a natural biodegradable polymer selected from the group consisting of chitosan, collagen and inorganic hydroxyapatite, a copolymer thereof, or a mixture thereof.
  • PGA poly glycolic acid
  • PLA poly lactic acid
  • PLGA poly(DL-lactic- co-glycolic acid)
  • a natural biodegradable polymer selected from the group consisting of chitosan, collagen and
  • the solvent for dissolving the polymer may be selected from among solvents known in the art, depending on the kind of polymer.
  • solvents known in the art for example, for chitosan, collagen or gelatin, acetic acid can be used as the solvent, and for polyvinyl alcohol), ultrapure water can be used as the solvent.
  • an organic solvent such as methylene chloride (CH 2 CI 2 ) or chloroform can be used.
  • the polymer is chitosan, and the corresponding solvent is an aqueous acetic acid solution.
  • the chitosan has a very high affinity for human cells, and thus when it is applied to an affected part, it will promote healing, because it is analgesic, has a moisture absorption property, promotes the formation of skin cells and shows antibiotic activity, and it will be naturally degraded in vivo.
  • the inventive method for preparing the porous polymer scaffold preferably further comprise, after the step (a), a step of mixing the polymer solution with an emulsifier, preferably one selected from the group consisting of butanol, pentanol, hexanol and octanol.
  • an emulsifier preferably one selected from the group consisting of butanol, pentanol, hexanol and octanol.
  • the addition of the emulsifier can form fine pores. This is because the solute, the solvent 1 and the solvent 2 (emulsifier such as butanol) are separated in different ways during phase separation, such that the solvent 2 (butanol) in the aqueous acetic acid solution containing chitosan is frozen to have small size, and thus large pores and fine pores are formed.
  • the step b) preferably comprises breaking dry ice into small pieces. This allows the polymer solution to be uniformly cooled and promotes the formation of the slush-like material. However, it is not necessary to break dry ice into small pieces, and during the process of mixing a lump of dry ice with the polymer solution, the distribution of dry ice changes and the size thereof naturally decreases due to sublimation.
  • the stirring in the step c) is preferably carried out when the solution starts to freeze, thus forming a soft slush-like material.
  • the step d) preferably further comprises, after placing the slush-like material into the predetermined container or mold, a step of centrifuging the slush-like material to remove bubbles.
  • a step of centrifuging the slush-like material In the centrifugation step, bubbles formed by mixing and the sublimation of dry ice can be removed.
  • the porosity and pore size of the porous polymer scaffold can be controlled by changing centrifugal force (turning force).
  • the step d) preferably comprises freezing the slush-like material in a deep freezer, followed by drying in a freeze dryer.
  • a porous polymer scaffold prepared according to the inventive preparation method which has uniform pores throughout the three-dimensional structure thereof.
  • the porous polymer scaffold prepared according to the preparation method of the present invention has uniform pore size distribution throughout the three-dimensional structure thereof and has a specific surface area significantly larger than that of a polymer scaffold prepared according to the prior method.
  • the three-dimensional porous polymer scaffold having suitable porosity and good interconnection between pores, provides a surface area required for the adhesion of cells and ensures a space, which is required for the regeneration of extracellular matrixes and for effective mass transfer for smooth supply of oxygen and nutrients in ex vivo culture.
  • the three-dimensional porous polymer scaffold is preferably a porous scaffold having a structure in which pores having a size in a specific range are uniformly distributed to maintain a given mechanical strength.
  • the porous polymer scaffold of the present invention preferably further comprises drugs required for wound healing, for example, antibiotics or antiinflammatory drugs, or growth factors required for cell culture, for example, bFGF, VEGF, TGF-beta or insulin.
  • drugs required for wound healing for example, antibiotics or antiinflammatory drugs
  • growth factors required for cell culture for example, bFGF, VEGF, TGF-beta or insulin.
  • Preparation methods of scaffolds containing such growth factors are well known in the art to which the present invention pertains (see VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res. 2006 May; 21 (5):735-44; Controlled release of bioactive TGF-beta 1 from microspheres embedded within biodegradable hydrogels, etc.).
  • a scaffold for three-dimensional cell culture which comprises the porous polymer scaffold according to the present invention.
  • the cell culture scaffold according to the present invention may further comprise the above-described growth factors.
  • tissue engineering scaffold comprising the porous polymer scaffold according to the present invention.
  • tissue engineering scaffold include scaffolds for tissue regeneration, such as artificial skins, artificial bones and artificial joints.
  • a wound dressing comprising the porous polymer scaffold according to the present invention.
  • the wound dressing of the present invention may further comprise a drug required for wound healing.
  • FIG. 1 shows the transfer direction of cold air in the preparation of a porous polymer scaffold according to the prior freeze drying method (left), and shows nonuniform pores in the resulting scaffold (right).
  • FIG. 2 is a schematic diagram showing a process of preparing a porous polymer scaffold using a slush method according to the present invention.
  • FIG. 3 shows an SEM photograph of the three surfaces of a porous scaffold prepared according to the slush method of the present invention (Example 1), an SEM photograph of the three surfaces of a porous scaffold prepared according to the prior freeze-drying method (Comparative Example 1), and an SEM photograph of the three surfaces of a porous scaffold having fine pores formed using only an emulsifier without dry ice (Comparative Example 2).
  • FIG. 4 is an SEM photograph showing the enlarged cross section of each of porous scaffolds prepared in Example 1 of the present invention, Comparative Example 1 and Comparative Example 2.
  • FIG. 5 is a photograph showing the comparison of the absorption time of an aqueous toluidine blue solution between porous scaffolds prepared in Example 1 of the present invention, Comparative Example 1 and Comparative Example 2.
  • FIG. 6 is a graphic diagram showing the comparison of tensile strength between Example 1 of the present invention, Comparative Example 1 and Comparative Example 2.
  • FIG. 7 is a photograph of HDF cells, which were stained with H&E after they were cultured on the porous scaffold prepared according to the method of Example 1 of the present invention.
  • FIG. 8 is a photograph of HDF cells, which were stained with H&E after they were cultured on the porous scaffold prepared according to the method of Comparative Example 1.
  • Example 1 Preparation of porous scaffold using dry ice 2 g of chitosan was dissolved in 100 ml of 1 % acetic acid aqueous solution. The chitosan solution was filtered, if necessary, to remove impurities. 40 g of 1 % acetic aqueous solution was added to and uniformly mixed with 100 g of the chitosan solution, and 10 g of an emulsifier was added thereto.
  • the emulsifier it is possible to use penthanol, hexanol or octanol, and preferably buthanol.
  • the resulting solution had a chitosan concentration of 1 % and a butanol concentration of 10% and became a suspension.
  • Dry ice was added to the prepared solution. Herein, if necessary, the dry ice can be broken into small pieces in order to facilitate processing.
  • the solution started to freeze, the solution was well stirred to form a soft slush-like material.
  • the slush-like material was placed in a predetermined container or mold, and if necessary, subjected to a process such as centrifugation to remove bubbles. Then, the slush-like material was frozen in a deep freezer, and then dried in a freeze dryer overnight. Then, the molded porous material was washed several times with alcohol.
  • FIG. 2 is a schematic diagram showing the process of preparing the porous polymer scaffold using the slush method according to the present invention.
  • a polymer such as PGA, PLA or PLGA can be used together with dry ice in order to prepare a porous scaffold according to the prior known freeze drying method (see Development of biodegradable porous scaffolds for tissue engineering, Materials Science and Engineering C 17 (2001), pp. 63-69).
  • a porous scaffold was prepared using chitosan in the same manner as in Example 1 , except that the process of adding dry ice was eliminated.
  • Comparative Example 2 Preparation of porous scaffold using emulsifier A porous scaffold was prepared without using dry ice in the same manner as in Comparative Example 1 , except that an emulsifier was added to form fine pores.
  • FIG. 3 shows an SEM photograph at 20Ox magnification of the three surfaces of a porous scaffold prepared according to the slush method of the present invention (Example 1), an SEM photograph at 20Ox magnification of the three surfaces of a porous scaffold prepared according to the prior freeze-drying method (Comparative Example 1), and an SEM photograph at 20Ox magnification of the three surfaces of a porous scaffold having fine pores formed using only an emulsifier without dry ice (Comparative Example 2). As shown in FIG.
  • Example 4 is an SEM photograph showing the enlarged cross section of each of porous scaffolds prepared in Example 1 of the present invention, Comparative Example 1 and Comparative Example 2.
  • Comparative Example 1 has large pores and non-uniform pore distribution
  • Comparative Example 2 has uniform pore distribution, but has a layered pore structure, which can adversely affect cells.
  • Example 1 of the present invention has uniform pores throughout thereof. From the results of the above-describe SEM observation, it can be seen that the porous material prepared using the slush method of the present invention has uniform pores through the three- dimensional structure thereof.
  • the porous scaffold of the present invention will have improved functions by overcoming the shortcomings of the prior method.
  • the specific surface area and average pore diameter of the porous scaffold prepared according to each of the methods of Example 1 of the present invention 1 , Comparative Example 1 and Comparative Example 2 were measured with a mercury porosimeter (Pascal 140+440, Thermo Finnigan).
  • the measurement results are shown in Table 1 below. From the results in Table 1 , it can be seen that the specific surface area of Example 1 is significantly larger than those of Comparative Examples 1 and 2 due to uniform pores.
  • a larger surface area of a porous material means that the porous material has a higher function.
  • the porous material of Example 1 has an increased area for contact with cells, and thus has an excellent function as a cell culture scaffold. In addition, it has a small contact angle such that liquid drops can be absorbed into the surface thereof, and thus it will also be highly useful as a wound dressing.
  • Comparative Example 1 and Comparative Example 2 In order to test the water absorption of the porous scaffold prepared according to each of the method of Example 1 of the present invention, Comparative Example 1 and Comparative Example 2, the three completely dried samples, each having a size of 200 mm x 200 mm, were weighed, and then simultaneously immersed in 100 ml of triple distilled water. After 30 seconds, the samples were taken out, left to stand on a dried Petri dish for 10 seconds and shaken 2-3 times to confirm that no water drops fell, and the weight thereof was measured. The measurement results are shown in Table 2 below. From the results in Table 2, the porous material of Example 1 , prepared using the slush method, showed the highest water absorption.
  • FIG. 5 is a photograph showing the comparison of the absorption time of an aqueous toluidine blue solution between the porous scaffolds prepared in Example 1 of the present invention, Comparative Example 1 and Comparative Example 2.
  • the horizontally spread diameter of the toluidine blue solution was the largest in the case of Comparative Example 1 and the smallest in the case of Example 1. This is considered to be because of the difference in absorption time.
  • the absorption rate of the toluidine blue solution into the sample was slow, and thus the toluidine blue solution was widely spread in the transverse direction
  • the absorption rate of the toluidine blue solution into the sample was fast, and thus the toluidine blue solution was narrowly spread in the transverse direction.
  • the scaffold of the present invention will be useful as a wound dressing.
  • Example 5 Measurement of tensile strength
  • FIG. 6 is a graphic diagram showing the comparison of tensile strength between Example 1 of the present invention, Comparative Example 1 and Comparative Example 2.
  • the porous material of Comparative Example 1 showed a high standard deviation in tensile strength.
  • the porous material of Comparative Example 2 having fine pores, showed a low standard deviation in tensile strength, but had low tensile strength.
  • the porous material of Example 1 prepared using the slush method, showed the lowest standard deviation and the highest tensile strength. This is considered to be because the porous material of the present invention had large surface area and uniform pore distribution, and thus showed high tensile strength compared to the porous materials prepared according to the prior methods. Accordingly, the porous material of the present invention can be used in various applications and shows improved physical properties, compared to the porous materials prepared according to the prior methods. [Table 3]
  • FIG. 7 is a photograph of HDF cells, which were stained with H&E after they were cultured for 3 weeks on the porous scaffold prepared according to the method of Example 1 of the present invention. As can be seen in FIG. 7, the HDF cells reached the inside of the porous scaffold, because opened pores were formed throughout the three-dimensional structure of the porous scaffold.
  • FIG. 7 is a photograph of HDF cells, which were stained with H&E after they were cultured for 3 weeks on the porous scaffold prepared according to the method of Example 1 of the present invention. As can be seen in FIG. 7, the HDF cells reached the inside of the porous scaffold, because opened pores were formed throughout the three-dimensional structure of the porous scaffold.
  • FIG. 7 is a photograph of HDF cells, which were stained with H&E after they were cultured for 3 weeks on the porous scaffold prepared according to the method of Example 1 of the present invention. As can be seen in FIG. 7, the HDF cells reached the inside of the porous scaffold, because opened pores were formed throughout the three-dimensional structure of the porous scaffold.
  • FIG. 8 is a photograph of HDF cells, which were stained with H&E after they were cultured for 7 days on the porous scaffold prepared according to the method of Comparative Example 1.
  • the arrow indicates the frame direction of the scaffold, and the downward direction from the upper surface does not coincide with the upward direction from the lower surface.
  • the porous material prepared through the prior freeze-drying method has a problem in that the size and shape of pores formed in the porous material are different between the surface and inside of the porous material.
  • the method of the present invention can solve the above problem and prepare a porous material in which uniform and opened pores are formed.
  • the present invention provides a method for preparing a porous material through freeze drying, in which a polymer solution for forming the porous material is rapidly cooled before it is frozen, such that the temperature gradient occurring in the freezing process is minimized, and thus pores are uniformly distributed in the porous material.
  • the present invention allows pores to be formed uniformly throughout the three-dimensional structure of the porous material.
  • the porous material prepared according to the present invention shows high specific area, increased water absorption and excellent strength, and thus is highly useful as a wound dressing and a scaffold.
  • the inventive porous material can overcome the limitations of the prior porous materials, caused by low physical properties, because it has increased strength.
  • the porous scaffold prepared according to the method of the present invention can be used not only as a tissue engineering scaffold, but also in all industrial applications which can good effects due to porosity, for example, wound dressings.

Abstract

L'invention concerne un procédé de préparation d'un échafaudage polymère poreux, permettant de répartir uniformément la taille et la forme des pores dudit échafaudage sur toute sa structure tridimensionnelle par la mise en œuvre d'un procédé de lyophilisation. L'invention concerne plus particulièrement un procédé de préparation d'échafaudage polymère poreux pouvant servir d'échafaudage à une culture cellulaire tridimensionnelle, d'échafaudage de génie tissulaire ou de pansement. Ce procédé se caractérise en ce qu'il comprend, en plus des étapes du procédé antérieur de lyophilisation, une étape de mélange de solution polymère avec de la glace sèche pour former un matériau de type bouillie de glace.
PCT/KR2007/001972 2007-04-23 2007-04-23 Procede de preparation d'un echafaudage polymere poreux a partir de glace seche WO2008130068A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/KR2007/001972 WO2008130068A1 (fr) 2007-04-23 2007-04-23 Procede de preparation d'un echafaudage polymere poreux a partir de glace seche

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2007/001972 WO2008130068A1 (fr) 2007-04-23 2007-04-23 Procede de preparation d'un echafaudage polymere poreux a partir de glace seche

Publications (1)

Publication Number Publication Date
WO2008130068A1 true WO2008130068A1 (fr) 2008-10-30

Family

ID=39875585

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2007/001972 WO2008130068A1 (fr) 2007-04-23 2007-04-23 Procede de preparation d'un echafaudage polymere poreux a partir de glace seche

Country Status (1)

Country Link
WO (1) WO2008130068A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101837148A (zh) * 2010-03-31 2010-09-22 四川科伦新光医药有限公司 一种多孔性可生物降解支架及其制备方法
CN102309782A (zh) * 2011-09-02 2012-01-11 西安交通大学 一种基于活细胞的复杂三维微通道多孔支架的制备方法
CN102641521A (zh) * 2012-04-24 2012-08-22 浙江大学 一种聚酯微球堆积型多孔支架的制备方法
CN102813562A (zh) * 2011-06-10 2012-12-12 冯淑芹 三维大孔径纳米级纤维支架与制备方法
CN102871772A (zh) * 2011-07-13 2013-01-16 冯淑芹 一种多孔可降解血管及其制备方法
US8435552B2 (en) 2007-02-09 2013-05-07 Royal College Of Surgeons In Ireland Collagen/hydroxyapatite composite scaffold, and process for the production thereof
WO2013071316A3 (fr) * 2012-12-28 2013-11-21 Starbard Nathan T Particules polymères poreuses et leurs procédés de fabrication et d'utilisation
CN104958785A (zh) * 2015-06-05 2015-10-07 中国人民解放军军事医学科学院卫生装备研究所 一种具有二级三维结构的复合骨修复材料及其制备方法
CN107715175A (zh) * 2017-09-30 2018-02-23 南京师范大学 一种plga/两性离子复合多孔骨组织工程支架及其制备方法
CN108893872A (zh) * 2018-08-07 2018-11-27 湖南工业大学 一种三维蓬松多孔支架的制备方法
CN110665068A (zh) * 2019-09-17 2020-01-10 东南大学 一种含定向通孔结构的聚乳酸多孔骨修复材料及其制备方法
US20200291348A1 (en) * 2017-11-21 2020-09-17 Corning Incorporated Dissolvable foam scaffolds for cell culture and methods of making the same

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4925924A (en) * 1984-03-27 1990-05-15 University Of Medicine And Dentistry Of New Jersey Biocompatible synthetic and collagen compositions having a dual-type porosity for treatment of wounds and pressure ulcers and therapeutic methods thereof
US4970298A (en) * 1984-03-27 1990-11-13 University Of Medicine And Dentistry Of New Jersey Biodegradable matrix and methods for producing same
US5863551A (en) * 1996-10-16 1999-01-26 Organogel Canada Ltee Implantable polymer hydrogel for therapeutic uses
US6899915B2 (en) * 2000-11-29 2005-05-31 President And Fellows Of Harvard College Methods and compositions for culturing a biological tooth

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4925924A (en) * 1984-03-27 1990-05-15 University Of Medicine And Dentistry Of New Jersey Biocompatible synthetic and collagen compositions having a dual-type porosity for treatment of wounds and pressure ulcers and therapeutic methods thereof
US4970298A (en) * 1984-03-27 1990-11-13 University Of Medicine And Dentistry Of New Jersey Biodegradable matrix and methods for producing same
US5863551A (en) * 1996-10-16 1999-01-26 Organogel Canada Ltee Implantable polymer hydrogel for therapeutic uses
US6899915B2 (en) * 2000-11-29 2005-05-31 President And Fellows Of Harvard College Methods and compositions for culturing a biological tooth

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9138483B2 (en) 2007-02-09 2015-09-22 Royal College Of Surgeons In Ireland Collagen/hydroxyapatite composite scaffold, and process for the production thereof
US8435552B2 (en) 2007-02-09 2013-05-07 Royal College Of Surgeons In Ireland Collagen/hydroxyapatite composite scaffold, and process for the production thereof
CN101837148A (zh) * 2010-03-31 2010-09-22 四川科伦新光医药有限公司 一种多孔性可生物降解支架及其制备方法
CN102813562A (zh) * 2011-06-10 2012-12-12 冯淑芹 三维大孔径纳米级纤维支架与制备方法
CN102871772A (zh) * 2011-07-13 2013-01-16 冯淑芹 一种多孔可降解血管及其制备方法
CN102309782A (zh) * 2011-09-02 2012-01-11 西安交通大学 一种基于活细胞的复杂三维微通道多孔支架的制备方法
CN102641521A (zh) * 2012-04-24 2012-08-22 浙江大学 一种聚酯微球堆积型多孔支架的制备方法
WO2013071316A3 (fr) * 2012-12-28 2013-11-21 Starbard Nathan T Particules polymères poreuses et leurs procédés de fabrication et d'utilisation
CN104958785A (zh) * 2015-06-05 2015-10-07 中国人民解放军军事医学科学院卫生装备研究所 一种具有二级三维结构的复合骨修复材料及其制备方法
CN107715175A (zh) * 2017-09-30 2018-02-23 南京师范大学 一种plga/两性离子复合多孔骨组织工程支架及其制备方法
US20200291348A1 (en) * 2017-11-21 2020-09-17 Corning Incorporated Dissolvable foam scaffolds for cell culture and methods of making the same
CN108893872A (zh) * 2018-08-07 2018-11-27 湖南工业大学 一种三维蓬松多孔支架的制备方法
CN108893872B (zh) * 2018-08-07 2021-11-09 湖南工业大学 一种三维蓬松多孔支架的制备方法
CN110665068A (zh) * 2019-09-17 2020-01-10 东南大学 一种含定向通孔结构的聚乳酸多孔骨修复材料及其制备方法

Similar Documents

Publication Publication Date Title
WO2008130068A1 (fr) Procede de preparation d'un echafaudage polymere poreux a partir de glace seche
Reverchon et al. Supercritical fluids in 3-D tissue engineering
US7022522B2 (en) Macroporous polymer scaffold containing calcium phosphate particles
EP1030697B1 (fr) Squelette de polymere biodegradable
Ma et al. A preliminary in vitro study on the fabrication and tissue engineering applications of a novel chitosan bilayer material as a scaffold of human neofetal dermal fibroblasts
JP5154729B2 (ja) 多孔質人工骨移植片およびその製造方法
US6472210B1 (en) Polymer scaffold having microporous polymer struts defining interconnected macropores
Do Kim et al. Effect of PEG–PLLA diblock copolymer on macroporous PLLA scaffolds by thermally induced phase separation
AU714647B2 (en) Polysaccharide sponges for cell culture and transplantation
KR101652582B1 (ko) 조직 및 뼈 재생을 위한 실크 피브로인 다공성 3차원 지지체 제작 방법
US10046088B2 (en) Nanoscale collagen particles and membranes
KR101181738B1 (ko) 다공성 3차원 나노섬유 스캐폴드의 제조방법
WO2002062968A2 (fr) Matieres microtubulaires et constructions de matieres/cellules
Zhang et al. Pore architecture and cell viability on freeze dried 3D recombinant human collagen-peptide (RHC)–chitosan scaffolds
AU2010234800B2 (en) Thick foams for biomedical applications and methods of making
AU762250B2 (en) Macroporous chitosan beads and preparation method thereof
JP2004501700A (ja) 連通セルを用いた三次元構造を有する生体適合性ポリマー、その調製方法、および医薬ならびに手術における適用
KR100979628B1 (ko) 균일한 다공구조를 갖는 조직공학용 다공성 입자 및 이의제조방법
Wibowo et al. Development of salt leached silk fibroin scaffold using direct dissolution techniques for cartilage tissue engineering
Mohammadi et al. Osteogenic differentiation of mesenchymal stem cells on novel three-dimensional poly (L-lactic acid)/chitosan/gelatin/b-tricalcium phosphate hybrid scaffolds
Wang et al. Polylactic acid scaffold with directional porous structure for large-segment bone repair
Sultana et al. Fabrication of gelatin scaffolds using thermally induced phase separation technique
Qi et al. Preparation and properties of a biodegradable poly (lactide-co-glycolide)/poly (trimethylene carbonate) porous composite scaffold for bone tissue engineering
Agarwal et al. Fabrication and morphological analysis of gelatin-alginate scaffolds
KR100844016B1 (ko) 드라이아이스를 이용한 다공성 고분자 스캐폴드의 제조방법

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07746134

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07746134

Country of ref document: EP

Kind code of ref document: A1