WO2013071062A1 - Échafaudage tubulaire de collagène multicouches - Google Patents
Échafaudage tubulaire de collagène multicouches Download PDFInfo
- Publication number
- WO2013071062A1 WO2013071062A1 PCT/US2012/064388 US2012064388W WO2013071062A1 WO 2013071062 A1 WO2013071062 A1 WO 2013071062A1 US 2012064388 W US2012064388 W US 2012064388W WO 2013071062 A1 WO2013071062 A1 WO 2013071062A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- collagen
- directions
- angle
- tube
- layers
- Prior art date
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
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/60—Materials for use in artificial skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments
Definitions
- Tissue engineering improves the health and quality of life by restoring, maintaining, or enhancing tissue/organ functions.
- tissue-engineering blood vessels have been used to replace or bypass blood vessels that have narrowed or are even blocked due to disease processes.
- tissue engineering Requirements for tissue engineering are high. Take tissue-engineered blood vessels for example. They should adapt to remodeling according to the needs of the environment. Also, they should induce little or no immunologic reaction. In addition, they should have high and long-term patency rates, high burst strength, low compliance mismatch, high infection resistance, and off-the-shelf availability. Further, they should have adequate mechanical strength so as to securely affix themselves to target sites.
- One aspect of this invention relates to a collagen scaffold including 2-10 stacked collagen fiber layers each having a thickness of 10-100 ⁇ .
- each layer at least 90% of the collagen fibers have a length of 2 mm or greater and are so oriented that they extend along the layer and are parallel to each other.
- Each layer features a direction identical to and defined by the orientation of the at least 90% of the collagen fibers, the direction being 30°-90° (e.g., 45°-90°, 60°-90°, and 80°-90°) relative to the direction of each collagen fiber layer next thereto.
- the collagen fiber layers in the collagen scaffold can be obtained from natural sources, e.g., tendon, bone, skin, and ligament.
- the collagen scaffold of this invention can include 1-9 non-collagen elastic layers, each of which is deposited in between two collagen fiber layers.
- the collagen scaffold can also include on its surface a polymer coating, which optionally contains a biologically active agent.
- Another aspect of this invention relates to a method of producing the collagen scaffold described above.
- the method includes first providing layers (each being 10- 100 ⁇ in thickness) of collagen fibers, at least 90% of which in each layer have a length of 2 mm or greater and are so oriented that they extend along the layer and are parallel to each other, thereby defining the direction of that layer; and then stacking the layers of collagen fibers in such a manner that the angle between the directions of any two layers next to each other is 30°-90°.
- the tubular wall includes 2-10 stacked collagen fiber layers, wherein at least 90% of the collagen fibers have a length of 2 mm or greater and are so oriented that they extend along the layer and are parallel to each other, and each layer has a thickness of 10- 100 ⁇ and a direction identical to the orientation of the at least 90% of the collagen fibers, the direction being 30°-90° (e.g., 45°-90°, 60°-90°, and 80°-90°) relative to the direction of each collagen fiber layer next thereto.
- a further aspect of this invention relates to a method of producing a collagen tube.
- the method includes the steps of making the collagen scaffold as described above and further wrapping the collagen scaffold around a cylindrical object having a diameter of 0.1-10 mm and removing the cylindrical object to provide a tube having collagen tubular wall.
- Figure 1 is a bi-layered collagen scaffold of this invention.
- Figure 2 is an illustration of a process of making the multi-layered collagen scaffold of this invention.
- Figure 3 is a SEM image of the collagen fiber layers of the collagen tube of this invention.
- Figure 4 is an optical image of two collagen fiber layers of the collage tube of this invention.
- Figure 5 is a diagram showing the stress-strain behaviors of various collagen scaffolds.
- Figure 6 is an image of a part of a tube wall in which PC 12- neuron cells grow along the collagen fibers.
- FIG. 1 shows a collagen scaffold having 2 stacked collagen layers, i.e., layers 101 and 102, each of which has a thickness (t) of 10-100 ⁇ .
- Collagen fibers (not shown) having a length of at least 2 mm extend along the layers.
- a substantial amount e.g., at least 80%, 85%, 90%, 95%, or 99%
- the orientation of a substantial amount of the collagen fibers is shown as direction 104.
- the angle between the directions of layers 101 and 102 is 30°-90°, 45°-90°, 60°-90°, or 80°-90°.
- Collagen fiber layers next to each other refer to two closest collagen fiber layers that are either in contact with each other or separated by one or more non-collagen layers.
- the collagen scaffolds of this invention can be prepared by the process illustrated in the scheme shown in Figure 2. Natural collagen sources are cut into small pieces and decellularized to obtain small collagen blocks. See J. Physiol. 567.3 (2005) pp 1021— 1033. The order of the cutting and decellularization steps can alter. Natural collagen sources include, but are not limited to, human or animal tendon, bone, skin, cartilage, ligament, and blood vessels. Cutting can be performed by any conventional method. The small pieces after cutting typically have a size in the range of 1-100 mm.
- Decellularization can be accomplished using one or more decellularization agents selected from detergents, emulsification agents, proteases, and ionic strength solutions. See U.S. Patent 6,962,814 for suitable decellularization agents and conditions.
- Decellularization preferably does not cause gross alteration in the structure of the tissue or cause substantial alteration in its biomechanical properties.
- decellularization on structure can be evaluated by light microscopy and/or ultrastructural examination.
- the decellularized tissue is washed in a physiologically appropriate solution, e.g., PBS or tissue culture medium. Washing removes residual decellularization solution that might otherwise cause deterioration of the decellularized tissue, inhibit the growth of subsequently seeded cells, and reduce biocompatibility.
- a physiologically appropriate solution e.g., PBS or tissue culture medium. Washing removes residual decellularization solution that might otherwise cause deterioration of the decellularized tissue, inhibit the growth of subsequently seeded cells, and reduce biocompatibility.
- the collagen blocks are then cut into slices having a predetermined thickness of
- the collagen blocks are frozen at a low temperature and then fixed to the cutting base plate of a cryostat with optimal cutting temperature (OCT) compound, e.g., Tissue- Tekl ® (Sakura Finetek USA, Inc., Torrance, CA), which contains polyvinyl alcohol and polyethylene glycol.
- OCT optimal cutting temperature
- the frozen collagen blocks are then cut by a microtome into collagen slices. Preferably, they are cut along the direction parallel to the orientation of the collagen fibers in the blocks so that the collagen fibers extend along the obtained slices.
- the stack of collagen slices can be compressed or collagen slices can be held together by applying a binder, e.g., fibrinin glue, poly(lactic-co-glycolic acid), or silicone.
- a binder e.g., fibrinin glue, poly(lactic-co-glycolic acid), or silicone.
- the layers (i.e., slices) of the collagen scaffold can be chemically bonded to further enhance their interaction.
- the collagen fibers on the surface of two adjacent layers can be cross-linked by a chemical cross-linking agent (e.g., an aldehyde compound or a carbodimiide) or heat (dehydrothermal cross-linking).
- a chemical cross-linking agent e.g., an aldehyde compound or a carbodimiide
- heat dehydrothermal cross-linking
- Formaldehyde is a preferred cross-linking agent, given its high vapor pressure and its safe use in implantable devices.
- the collagen fibers can also be cross-linked by plasma or any other known method.
- the extent of the cross-linking can be controlled by the concentration of the cross-linking agent, the time for the cross-linking reaction, and the temperature (if the agent is in liquid form), or the vapor pressure (if the agent is in gas form), under which the cross-linking reaction is carried out.
- the collagen scaffolds of this invention have good isotropic and mechanical properties due to different collagen fiber orientations of neighboring layers in the scaffolds.
- the angle of the carbon fiber orientations of two neighboring collagen fiber layers can be set to 45°-90°, 60°-90°, or 80°-90°.
- the collagen scaffolds of this invention can be used as bone, tendon, skin, cartilage, and blood vessel implants.
- cells e.g., endothelial cells or smooth muscle cells
- the collagen scaffolds can be treated with one or more biologically active agents.
- the agent(s) is selected to enhance the properties of a scaffold following implantation, e.g., to facilitate populating endogenous cells (i.e., cells present within the subject) in the scaffold, to enhance the growth of seeded cells, to facilitate vascularization of the scaffold, and to reduce the likelihood of thrombus formation.
- Appropriate biologically active agents include, but are not limited to, thrombomodulators, hemocompatible agents, and antibiotics.
- an agent is a pharmaceutical composition intended for treating the condition the same as, or different from, that being treated by implanting the scaffold.
- the collagen scaffolds of this invention can be configured to assume a particular desired shape and size by a known method.
- a tubular collagen scaffold can be made by wrapping a collagen scaffold (prepared by the process described above) that is in sheet form around a cylindrical object having a predetermined diameter (e.g., 0.1 to 1 mm).
- a tubular collagen scaffold is suitable for use as a replacement for a damaged blood vessel or as a nerve conduit that promotes nerve growth.
- one aspect of this invention relates to a collagen tube including a tubular wall, i.e., a tubular collagen scaffold, which contains 2-10 stacked collagen fiber layers.
- one or more biologically active agents can be incorporated into the layers of the collagen tube of this invention to promote tissue engineering of a blood vessel or nerve or to prevent tissue adhesion. Examples include but are not limited to growth factors (e.g., the vascular endothelial growth factor), cytokines, laminins,
- the biologically active agent can be incorporated into the layers via electrostatic interaction, physical or mechanical interaction, covalent bonding using crosslinking agents or light, a combination of the above, or via a spacer molecule that is well known in the art.
- a biologically active agent for example, one can immerse collagen layers into a solution containing a biologically active agent before stacking them or immerse the stacked collagen layers into such a solution.
- the collagen tube can be coated with poly(dimethylsiloxane), poly(lactic-co- glycolic acid), polystyrene, silk, or hydrogels to improve mechanical properties of the tube.
- the above-mentioned biologically active agents can be included in the polymer coatings. Controlled release of these biologically active agents can therefore be achieved.
- the surfaces of the collagen tube can be treated to introduce the desirable hydrophilic nature so as to support biocompatibility.
- the pH value of the collagen tube surfaces can also be adjusted to prevent significant systemic or local reaction. See, e.g., Bostman et al, Biomaterials 2000, 21 :2615-2621.
- Non-collagen layer refers to a layer containing no collagen at all or an unsubstantial amount of collagen.
- the elastic non- collagen layer can be made a biocompatible material, such as a natural material (e.g., a slice of an aorta vessel wall) or a synthetic material (e.g., a synthetic polymer slice).
- suitable synthetic polymers include poly(glycerol sebacatej, silicone, or polyurethane.
- the collagen tube may also include one or more supportive layers.
- Such supportive layers can be placed between any two collagen fiber layers or attached to the inner or outer surface of the collagen tube wall.
- the collagen tube can further include cells (e.g., endothelial cells and smooth muscles cells) to promote tissue engineering.
- this process involves seeding (i.e., contacting) a collagen tube with cells and culturing the seeded tube under conditions suitable for growth of the cells. Examples of growth conditions include use of particular growth media and application of mechanical/electrical/chemical stimuli.
- the cells can be derived from an animal or a cell line of the same species as the intended recipient so that the resulting tube contains proteins that are minimally antigenic and maximally compatible in the recipient. For example, if the collagen tube is to be implanted into a human, the cells are preferably human cells.
- the collagen tube of this invention can be implanted into a patient to replace or bypass abnormal arteries and veins in conditions such as aneurysm and peripheral artery disease, or atherosclerosis or arteries and veins that are or blocked or damaged by injury or vascular disease, e.g., thrombosis or stroke.
- abnormal arteries and veins in conditions such as aneurysm and peripheral artery disease, or atherosclerosis or arteries and veins that are or blocked or damaged by injury or vascular disease, e.g., thrombosis or stroke.
- the collagen tube can also be used in nerve repairing.
- the linear nature of the collagen fibers provides an ideal structure to guide the growth of the neural cells.
- collagen tube can be used in urethral replacement or used as bioartificial renal tubular device in treating renal failure.
- Tendon was obtained from cow tendon or rat tail and cut into 10 x 10 x 3 mm blocks.
- the blocks were then placed into a surfactant solution (Tris buffer, 5 mM EDTA and 1% SDS) and placed on a shaker at 4°C for 48 h to remove cells.
- the tendon blocks were placed in deionized H 2 0 for 24 h at 4°C, and then removed from H 2 0, embedded in OCT media, and frozen at -20°C.
- the frozen blocks were sectioned with a cryostat microtome into slices having a thickness of 20-100 ⁇ depending on the desired properties. These square sections were stacked with alternating fiber orientations in groups of 2-10. The stacks were wrapped around a glass capillary tube and allowed to dry overnight.
- FIGS. 3 and 4 respectively show the SEM and optical images of the wall of a thus-obtained collagen tube.
- Collagen fiber tubes were cut into pieces of approximately 15 mm in length and 8 mm in width. Each piece was placed onto an Instron 3366 uniaxial material testing device equipped with a 100 N load cell. It was then subjected to a tensile stress at a strain rate of 0.5 mm/min until failure. The load-displacement data was collected and converted to stress-strain data based on initial dimensional measurements to ensure normalized comparison between samples of different sizes. Various sample configurations and orientations were tested to determine the structure having the optimal mechanical properties. The samples that displayed the optimal mechanical properties were then replicated and subjected to a hydrated testing. The samples were hydrated in phosphate buffered saline (PBS) for one hour prior to testing. An Instron testing apparatus was modified with a water bath filled with PBS. The testing was repeated and the data collected and analyzed in the same way as described above. The optimal biomechanical properties were then compared with cell viability data to determine the best scaffold construction technique.
- PBS phosphate buffered sa
- collagen fiber tubes having collagen fibers oriented in alternating directions as described above crossed sections
- collagen fiber tubes having all of the fibers aligned in the same direction and having the tensile force applied parallel to that direction linear sections
- collagen fiber tubes having all of the fibers aligned in the same direction and having the tensile force applied perpendicular to that direction antilinear sections.
- the collagen fiber tubes of this invention had preferred stress-strain properties. More specifically, crossed sections (i) had mechanical strength than linear sections (ii) and antilinear sections (iii).
- Collagen fiber tubes of this invention were also used to grow PC-2 neuron cells. Beef tendon was obtained and decellularized by extraction with Tris-HCl buffer, 5 mM EDTA, and 1% (w/v) SDS. The decellularized tendon was fixed in 4%
- the dehydrated tendon was either embedded into paraffin for traditional microtome sectioning, or sectioned directly without cryomicrotome.
- the tendon was cut along the longitudinal alignment of the collagen fibers, which were then transferred to a glass slide for further processing.
- the tendon slices were immersed in xylene to remove paraffin (when needed). All of the tendon slices were rehydrated by immersion in ethanol solutions with the gradually decreasing ethanol concentrations.
- the rehydrated slices were used as scaffolds for aligned and directionally guided nerve growth as follows.
- Cells of the PC 12 cell line, obtained from ATCC, were seeded onto the tendon slices with a density of 5 x 10 4 cells per well, or 1.3 x 10 4 cells/cm 2 in custom culture medium (89% v/v Dulbecco's Modified Eagle Medium, 5% v/v horse serum, 5% v/v fetal bovine serum, and 1% v/v Penicillin: Streptomycin solution).
- the cells were incubated at 37°C for ⁇ 24 hours not in any differentiation medium.
- the growth medium was then replaced with custom differentiation medium (97% v/v DMEM, 1% v/v Nerve Growth Factor, 1% v/v Horse Serum, 1% v/v Penicillin: Streptomycin solution).
- custom differentiation medium 97% v/v DMEM, 1% v/v Nerve Growth Factor, 1% v/v Horse Serum, 1% v/v Penicillin: Streptomycin solution.
- the cells were allowed to grow for 1 week, during which the medium was replaced every two days.
- the tendon slices were then removed from the medium, and fluorescence stained with 25 ⁇ ⁇ of Texas Red-x phalloidin in methanol and one drop of 4',6-diamidino-2- phenylindole solution per tendon. They were analyzed using light fluorescence microscopy. Scanning electron microscopy was used to image the tendon slices in greater detail. As shown in Figure 6, PC-2 neuron cells grew linearly along the collagen fibers in the tube wall.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Vascular Medicine (AREA)
- Biophysics (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
L'invention concerne un échafaudage de collagène comprenant 2-10 couches de fibres de collagène empilées, au moins 90 % des fibres de collagène dans chaque couche ayant une longueur d'au moins 2 mm et étant orientées de telle sorte qu'elles s'étendent le long de la couche et sont parallèles entre elles, chaque couche ayant une épaisseur de 10-100 µm et étant orientée selon une direction identique à l'orientation des au moins 90 % des fibres de collagène, et l'angle entre les directions de chaque couche de fibres de collagène l'une après l'autre étant de 30°-90°. L'invention concerne également un tube de collagène fait de l'échafaudage de collagène décrit ci-dessus.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US2013/028197 WO2014074134A1 (fr) | 2012-11-09 | 2013-02-28 | Echafaudage de collagène multicouche |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161557660P | 2011-11-09 | 2011-11-09 | |
US61/557,660 | 2011-11-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013071062A1 true WO2013071062A1 (fr) | 2013-05-16 |
Family
ID=48290587
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2012/064388 WO2013071062A1 (fr) | 2011-11-09 | 2012-11-09 | Échafaudage tubulaire de collagène multicouches |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2013071062A1 (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105688261A (zh) * | 2014-12-12 | 2016-06-22 | 财团法人工业技术研究院 | 复合材料 |
CN106390194A (zh) * | 2015-07-28 | 2017-02-15 | 中国科学院遗传与发育生物学研究所 | 用于修复尿道损伤的生物修复材料及其制备方法与应用 |
WO2019219916A3 (fr) * | 2018-05-18 | 2019-12-26 | Cambridge Enterprise Limited | Biomatériaux à base de collagène et procédés de fabrication de biomatériaux à base de collagène |
CN113559329A (zh) * | 2021-09-03 | 2021-10-29 | 北京大学口腔医学院 | 一种仿牙周有序双层结构支架材料及其制备方法和应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030133967A1 (en) * | 2000-03-09 | 2003-07-17 | Zbigniew Ruszczak | Multilayer collagen matrix for tissue reconstruction |
US6737053B1 (en) * | 1999-11-12 | 2004-05-18 | National University Of Singapore | Tissue-engineered ligament |
JP2004188037A (ja) * | 2002-12-12 | 2004-07-08 | Nipro Corp | コラーゲン製人工血管 |
US20060029639A1 (en) * | 2002-10-31 | 2006-02-09 | Yukihiro Morinaga | Biodegradable substrate, prosthetic material for tissue regeneration, and cultured tissue |
US20090069893A1 (en) * | 2007-04-19 | 2009-03-12 | Mikhail Vitoldovich Paukshto | Oriented Collagen-Based Materials, Films and Methods of Making Same |
US20100074874A1 (en) * | 2006-09-20 | 2010-03-25 | James Torbet | Synthetic multi-layer structures comprising biopolymer fibres |
-
2012
- 2012-11-09 WO PCT/US2012/064388 patent/WO2013071062A1/fr active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6737053B1 (en) * | 1999-11-12 | 2004-05-18 | National University Of Singapore | Tissue-engineered ligament |
US20030133967A1 (en) * | 2000-03-09 | 2003-07-17 | Zbigniew Ruszczak | Multilayer collagen matrix for tissue reconstruction |
US20060029639A1 (en) * | 2002-10-31 | 2006-02-09 | Yukihiro Morinaga | Biodegradable substrate, prosthetic material for tissue regeneration, and cultured tissue |
JP2004188037A (ja) * | 2002-12-12 | 2004-07-08 | Nipro Corp | コラーゲン製人工血管 |
US20100074874A1 (en) * | 2006-09-20 | 2010-03-25 | James Torbet | Synthetic multi-layer structures comprising biopolymer fibres |
US20090069893A1 (en) * | 2007-04-19 | 2009-03-12 | Mikhail Vitoldovich Paukshto | Oriented Collagen-Based Materials, Films and Methods of Making Same |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105688261A (zh) * | 2014-12-12 | 2016-06-22 | 财团法人工业技术研究院 | 复合材料 |
CN105688261B (zh) * | 2014-12-12 | 2019-07-09 | 财团法人工业技术研究院 | 复合材料 |
CN106390194A (zh) * | 2015-07-28 | 2017-02-15 | 中国科学院遗传与发育生物学研究所 | 用于修复尿道损伤的生物修复材料及其制备方法与应用 |
CN106390194B (zh) * | 2015-07-28 | 2019-05-07 | 中国科学院遗传与发育生物学研究所 | 用于修复尿道损伤的生物修复材料及其制备方法与应用 |
WO2019219916A3 (fr) * | 2018-05-18 | 2019-12-26 | Cambridge Enterprise Limited | Biomatériaux à base de collagène et procédés de fabrication de biomatériaux à base de collagène |
US11998655B2 (en) | 2018-05-18 | 2024-06-04 | Cambridge Enterprise Limited | Collagen biomaterials and methods for manufacturing collagen biomaterials |
CN113559329A (zh) * | 2021-09-03 | 2021-10-29 | 北京大学口腔医学院 | 一种仿牙周有序双层结构支架材料及其制备方法和应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2014074134A1 (fr) | Echafaudage de collagène multicouche | |
Kumar et al. | Acellular vascular grafts generated from collagen and elastin analogs | |
Park et al. | The significance of pore microarchitecture in a multi-layered elastomeric scaffold for contractile cardiac muscle constructs | |
US7550152B2 (en) | Tissue graft scaffold made from cholecyst-derived extracellular matrix | |
DE60214477T2 (de) | Implantat zur Regeneration von Knorpelgewebe | |
Raghavan et al. | Physical characteristics of small intestinal submucosa scaffolds are location‐dependent | |
Moreno et al. | Development of a compliant and cytocompatible micro‐fibrous polyethylene terephthalate vascular scaffold | |
JP7209377B2 (ja) | 組織工学医療デバイス | |
Madhavan et al. | Mechanical and biocompatible characterizations of a readily available multilayer vascular graft | |
US20070292514A1 (en) | Bioengineered Intervertebral Discs and Methods for Their Preparation | |
Ciolacu et al. | Natural polymers in heart valve tissue engineering: strategies, advances and challenges | |
EP3952934B1 (fr) | Structure d'échafaudage tubulaire équivalente à un tissu, et procédés de production de celle-ci | |
Song et al. | Effective seeding of smooth muscle cells into tubular poly (trimethylene carbonate) scaffolds for vascular tissue engineering | |
WO2013071062A1 (fr) | Échafaudage tubulaire de collagène multicouches | |
CN108136076B (zh) | 经培养的细胞小叶材料 | |
Santoro et al. | Feasibility of pig and human‐derived aortic valve interstitial cells seeding on fixative‐free decellularized animal pericardium | |
WO2006137546A1 (fr) | Méthode de traitement pour empêcher la calcification de tissu de transplantation d’origine biologique et tissu ainsi traité | |
Callanan et al. | The effects of stent interaction on porcine urinary bladder matrix employed as stent-graft materials | |
WO2017158148A1 (fr) | Polymères et leurs utilisations pour la fabrication de valvules cardiaques « vivantes » | |
US9308294B2 (en) | Synthetic serous membranes and methods for making the same | |
JP6529090B2 (ja) | in situティッシュ・エンジニアリング | |
Terazawa et al. | One-year follow-up study of iBTA-induced allogenic biosheet for repair of abdominal wall defects in a beagle model: a pilot study | |
Davis et al. | On the potential of hydrated storage for naturally derived ECMs and associated effects on mechanical and cellular performance | |
Kerdjoudj et al. | Decellularized umbilical artery treated with thin polyelectrolyte multilayer films: potential use in vascular engineering | |
Sharif et al. | Developing a synthetic composite membrane for cleft palate repair |
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: 12846864 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: 12846864 Country of ref document: EP Kind code of ref document: A1 |