CN101721751A - Human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and preparation method and applications thereof - Google Patents
Human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and preparation method and applications thereof Download PDFInfo
- Publication number
- CN101721751A CN101721751A CN200810224013A CN200810224013A CN101721751A CN 101721751 A CN101721751 A CN 101721751A CN 200810224013 A CN200810224013 A CN 200810224013A CN 200810224013 A CN200810224013 A CN 200810224013A CN 101721751 A CN101721751 A CN 101721751A
- Authority
- CN
- China
- Prior art keywords
- kernel
- growth factor
- hollow silica
- cell growth
- ball
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
Landscapes
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of bomedical material preparation, in particular relates to human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and a preparation method and applications thereofThe human tissue engineering support is prepared in the following steps: the hollow silicon dioxide submicron ball loaded with cell growth factors and provided with kernel is self-assembled with gelatin to form a compound ball which is composed of the hollow silicon dioxide submicron ball loaded with cell growth factors and provided with kernel and the gelatin; then the compound ball is loaded to macromolecule polymer fiber base material obtained by the electric spinning method, thus obtaining the human tissue engineering support.With hollow silicon dioxide submicron ball with kernel as a slow release carrier of the cell growth factors, cell proliferation and differentiation is promoted by loading and slowly releasing the cell growth factors.The human tissue engineering support of the invention is an all-round imitation of the cell growth microenvironment, thus enjoying broad application prospect in the field of tissue engineering support covering tissue repair and tissue reconstruction.
Description
Technical field
The invention belongs to the biomedical material preparing technical field, particularly load the human tissue engineering support and its production and use of hollow silica ball of controlled-release cell growth factor with kernel.
Background technology
The source scarcity of tissue, the particularly great organ of human body is the sick big obstacle that decreases tissue or human organ tissue transplantation of gentrify human body always; Be used for gentrify human body disease and decrease the human tissue engineering Products Development of the biological activity substitute of the structure of tissue or human organ, function, will help to improve greatly level of human health.The human tissue engineering product loads on a kind of good cell compatibility and can be by on the biomaterial of people's body degraded and absorbed of having with the normal tissue cell of people's cultured and amplified in vitro, then with load the disease of biomaterial composites implant into body tissue of the normal tissue cell disease of decreasing position or organ decrease the position, as the biomaterial of cell growth support gradually by people's body degraded and absorbed in, cell is propagation and differentiation constantly, and the disease that the disease that is formed on form and function aspect and tissue is decreased position or organ decreases the consistent new tissue of tissue at position, thereby reaches the purpose of repairing wound and rebuilding function.
Human tissue engineering support helps adhesion, propagation and the differentiation of cell for the cell that makes up tissue provides three-dimensional rack, for the cell growth provides suitable external environment.Ideal human tissue engineering support should possess following characteristics: 1) possess excellent biological compatibility, can not influence neoblastic function because of the rejection of adjacent tissue; 2) have degradability and suitable degradation rate, when the new human tissue cell of transplanting or tissue were survived in receptor, timbering material can be degraded voluntarily; 3) has the biomechanical strength that meets human body cell, human tissue organ's requirement; 4) have good human body cell interface relation, can interact to preserve and promotion human body cell function; 5) be convenient to be processed into ideal two dimension or three dimensional structure, and can keep original shape after being transplanted in the human body.
Except human tissue engineering support, cell growth factor is moved promoting the division growth of cell, and gene expression and differentiation play crucial effects.Add cell growth factor in cultivating system, the analog cell microenvironment can prolong the cell survival time, makes up the tissue with 26S Proteasome Structure and Function.Cell growth factor is compound to the focus that becomes in recent years research in the human tissue engineering support.
At present, developed the human tissue engineering support that several different methods prepares various structures, but the human tissue engineering support General Mechanics intensity difference that obtains, the function that do not possess controlled-release cell growth factor.Patent of invention " a kind of preparation method of chitosan tubulose support " (publication number: disclose a kind of preparation method of the chitosan tubulose support with Weaving method preparation CN1568904), but this support does not have the function of controlled-release cell growth factor; Patent of invention " a kind of construction method that contains the skin tissue engineering scaffold of epidermal growth factor " (publication number: obtain containing the skin tissue engineering scaffold of epidermal growth factor CN1511592) by freeze-drying, but the tissue engineering bracket intensity that obtains is relatively poor.
The present invention is directed to the demand of the outer cell culture of human body, prepared human tissue engineering support by simple preparation method design.This human tissue engineering support adopts the hollow silica sub-micron ball controlled-release cell growth factor with kernel, then self assembly is silicon dioxide/gelatin-compounded ball, load on the polymer fiber of electrical spinning method preparation, obtain human tissue engineering support.This human tissue engineering support comprehensive simulated human body cell microenvironment comprises micron and the nanostructured, controlled-release cell growth factor of the extracellular matrix of cell, possesses the ideal conditions of the high vigor cultivation of human body cell.This human tissue engineering support has favorable mechanical performance and cell compatibility, and is applied widely, can be used for the reparation of histoorgans such as bone, cartilage, nerve, blood vessel, bladder, kidney, liver.
Summary of the invention
One of purpose of the present invention the has provided load human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel.
The preparation method of human tissue engineering support of hollow silica ball of controlled-release cell growth factor that two of purpose of the present invention has provided load with kernel.
The purposes of the human tissue engineering support of the hollow silica ball with kernel of three of purpose of the present invention is loads controlled-release cell growth factor.
Load of the present invention the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, be that hollow silica sub-micron ball with kernel by having loaded cell growth factor and gelatin self assembly are to have loaded the composite balls that the hollow silica sub-micron ball with kernel of cell growth factor and gelatin are formed, then it loaded on the high molecular polymerization fibres for preparing by electrical spinning method and obtain as the human tissue engineering support base material.
Load of the present invention the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel be: on as the high molecular polymerization fibres of human tissue engineering support base material load the hollow silica sub-micron ball with kernel of controlled-release cell growth factor and the composite balls that gelatin is formed.The particle diameter of composite balls is 1 μ m～1000 μ m.
Also loaded nutrient substance in the composite balls that described hollow silica sub-micron ball with kernel and gelatin are formed, the composite balls of the hollow silica sub-micron ball with kernel with the gelatin composition of obtained on as the high molecular polymerization fibres of human tissue engineering support base material load controlled-release cell growth factor and nutrient substance.The particle diameter of composite balls is 1 μ m～1000 μ m.
Load of the present invention the preparation method of human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel may further comprise the steps:
1) the hollow silica sub-micron ball that will have a kernel is immersed in the cell growth factor aqueous solution, being 4 ℃ in temperature stirs down, be centrifugal under 4 ℃ in temperature then, with washed with de-ionized water gained solid product, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of cell growth factor;
2) loading that step 1) is obtained the hollow silica sub-micron ball ultra-sonic dispersion with kernel of cell growth factor in aqueous gelatin solution, lyophilization has then obtained loading the hollow silica sub-micron ball with kernel of cell growth factor and the composite balls that gelatin is formed;
3) with step 2) loading that obtains the hollow silica sub-micron ball with kernel of cell growth factor and the composite balls that gelatin is formed be dispersed in the alcohol solvent, add N-hydroxy-succinamide (NHS) and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides (EDC), fully reaction under the room temperature, use phosphate buffer (PBS) washing afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the high molecular polymer of human tissue engineering support base material; The composite balls of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid for preparing by electrical spinning method as the high molecular polymerization fibres of human tissue engineering support base material, 4 ℃ of reactions down, take out the high molecular polymerization fibres after soaking, with phosphate buffer washing, the human tissue engineering support of hollow silica ball of controlled-release cell growth factor that obtained load with kernel.
Be with 10 in the step 1)
-3It is 10 that the hollow silica sub-micron ball that～10g has a kernel is immersed in concentration
-3In the cell growth factor aqueous solution of～10mmol/L; In the cell growth factor aqueous solution, also further contain nutrient substance.
Step 2) final concentration of hollow silica sub-micron ball in aqueous gelatin solution with kernel that has loaded cell growth factor is 10
-3～100mg/mL, the mass concentration of aqueous gelatin solution is 0.05～10%; Perhaps step 2) final concentration of hollow silica sub-micron ball in aqueous gelatin solution with kernel that has loaded cell growth factor and nutrient substance is 10
-3～100mg/mL, the mass concentration of aqueous gelatin solution is 0.05～10%.
The hollow silica sub-micron ball with kernel of cell growth factor and the composite balls that gelatin is formed have been loaded in the step 3), perhaps loaded the hollow silica sub-micron ball with kernel of cell growth factor and nutrient substance and the composite balls that gelatin is formed, the concentration in alcohol solvent is 10
-2～10
2Mg/mL; N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in alcohol solvent is respectively 10
-7～10
-3Mol/L.
Contain in the phosphate-buffered dispersion liquid in the step 3) to pass through the high molecular polymerization fibres as the human tissue engineering support base material that electrical spinning method prepares be 10
-2～10
2Mg/ml.
Described nutrient substance is selected from vitamin A, vitamin B (comprises B1, B2, B6, B12, PP, inositol, M etc.), vitamin C, vitamin D, vitamin E, vitamin K, tryptophan, threonine, methionine, valine, lysine, leucine, isoleucine, phenylalanine, L-glutaminate, purine, pyrimidine, glucose, fructose, galactose, lactose, sucrose, maltose, cholic acid, choline, sterin, creatine, prostaglandin, epinephrine, insulin, cholesterol, phospholipid, glycolipid, hemoglobin, ribose, a kind of in the deoxyribose etc. or greater than more than one.
The times of stirring under temperature is 4 ℃ of step 1) are 12～72 hours.
Fully the time of reaction is 15～60 minutes under the room temperature of step 3); The time of reaction is 4～72 hours down at 4 ℃.
Described hollow silica sub-micron ball with kernel has the hollow meso-hole structure, as slow-released carrier, stimulates cell growth, propagation and the differentiation of human body by loading, slowly discharge cell growth factor.
The preparation of described hollow silica sub-micron ball with kernel and can be referring to number of patent application CN200610089184.9 and number of patent application CN200610113976.5 as slow-released carrier.
The particle diameter of described hollow silica sub-micron ball with kernel is between 100～1000nm, and outer casing thickness is between 20～200nm; It is the movably preparing spherical SiO 2 kernel of 50～500nm that one particle diameter is arranged in the cavity of this hollow silica sub-micron ball; This hollow silica sub-micron ball has meso-hole structure, and mesoporous aperture is 3～50nm; The specific surface area of this hollow silica sub-micron ball is 100～1000m
2/ g.
Wherein, be the described method of CN200610089184.9 according to number of patent application, be that the Fluohydric acid. molar concentration described in the CN200610089184.9 is from 1 * 10 with number of patent application
-3～5 * 10
-1Mol/L expands to 1 * 10
-4～10 * 10
-1Mol/L, the mesoporous average pore size that can obtain having the hollow silica sub-micron ball of kernel expands to 3～50nm by 3～10nm, and reference area is by 140～500m
2/ g expands to 140～1000m
2/ g.
Described cell growth factor is selected from transforming growth factor, epidermal growth factor, VEGF, basic fibroblast growth factor, nerve growth factor, the cartilage regulin, glial growth factor, platelet derivation somatomedin, hepatocyte growth factor, people's epithelial cells somatomedin, insulin like growth factor, a kind of in the bone morphogenetic protein etc. or greater than more than one.
The diameter of described high molecular polymerization fibres as the human tissue engineering support base material is 10nm～1000 μ m, and the compound human tissue engineering support diameter that has after the hollow silica sub-micron ball of kernel and the composite balls that gelatin is formed is 1010nm～2000 μ m.
Described high molecular polymer fiber is different with molecular weight according to selected type of polymer, is about 1 day～1 year at the intravital degradation time of people.High molecular polymer is an amino polyvinyl alcohol, hold amino polylactic acid, hold the statistic copolymer of amino lactide and Acetic acid, hydroxy-, bimol. cyclic ester, hold the random or block copolymer of amino lactide-ethylene glycol-Acetic acid, hydroxy-, bimol. cyclic ester, polymine, the polypropylene imines, polyethyene diamine, polyamide, poly-ethanolamine, hold amino Polyethylene Glycol, polylysine, poly-gamma-glutamic acid, poly-aspartate, poly arginine, poly-asparagine, chitin, chitosan, poly-amino-beta--cyclodextrin, gelatin, collagen, aminoglycan, fibroin, spider silk fibroin, aminocellulose or amino starch etc.
The processing of electricity consumption spinning equipment can be as the technology of the high molecular polymerization fibres of human tissue engineering support base material: the high molecular polymer spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 0.01ml/h～100ml/h, apply voltage 1～50kV and carry out the electrospinning silk, on the receptor at 0.1cm above the spinning nozzle～100cm place, obtain the high molecular polymerization fibres.
Load of the present invention controlled-release cell growth factor or further to contain the preparation cost of human tissue engineering support of the hollow silica ball with kernel of nutrient substance low, be fit to large-scale production, can be used as the support of the reparation or the reconstruction of various human soma or organ; Described tissue or organ comprise liver, nerve, bone, cartilage, kidney, bladder, blood vessel, skin or heart.
Load of the present invention the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel compare with existing human tissue engineering support, have the following advantages and outstanding effect: 1) human tissue engineering support of the present invention's preparation adopts the good material of biocompatibility, has hierarchy, specific surface area is big, helps cell adhesion and growth; 2) cell growth factor etc. is loaded in the hollow silica sub-micron ball with kernel, has saved the consumption of expensive cell growth factor greatly; 3) cell growth factor is contained in the hollow silica sub-micron ball with kernel, increases tropism and the adhesive force of cell, promote cell, thereby promote the release with extracellular matrix components of converging between the cell to the support internal breeding to support; 4) the high molecular polymerization fibres becomes tissue with cell proliferation, can be degraded fully, and the hollow silica with kernel can not cause organism immune response and inflammatory reaction with urine and defecate; 5) further contain nutrient substance and can play auxiliary curative effect the healing of wound.
The specific embodiment
Embodiment 1.
1.0.001g (particle diameter is 100nm, and outer casing thickness is 22nm, and mesoporous aperture is 3nm, and specific surface area is 100m to have the hollow silica sub-micron ball of kernel (kernel size for 50nm)
2/ g) be immersed in the 0.001mmol/L nerve growth factor aqueous solution, be 4 ℃ in temperature and stirred 12 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of nerve growth factor.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading nerve growth factor that will obtain is in mass concentration is 1% aqueous gelatin solution, and the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads nerve growth factor is 10
-3Mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of nerve growth factor and the composite balls that gelatin is formed.The particle diameter of composite balls is 1 μ m.
3. the 1g chitosan is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 0.1ml/h, applies voltage 5kV and carries out the electrospinning silk.On the receptor at 15cm place above the spinning nozzle, obtain chitin fiber.About 950 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of nerve growth factor and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded nerve growth factor is 1mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 10
-7Mol/L, mix homogeneously, room temperature was fully reacted 15 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the chitin fiber of human tissue engineering support base material.The composite balls 1mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the chitin fiber that step 3 prepares that concentration is 1mg/ml, 4 ℃ were reacted 4 hours down, take out the chitin fiber after soaking, wash about 3 times with phosphate buffer, but obtain the chitin fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded the slow release nerve growth factor.
When this human tissue engineering support can sustain damage at people's nerve, when nerve is repaired, its recovery support as nerve is used.
Embodiment 2.
1.10g (particle diameter is 980nm, and outer casing thickness is 20nm, and mesoporous aperture is 10nm, and specific surface area is 400m to have the hollow silica sub-micron ball of kernel (kernel size for 500nm)
2/ g) be immersed in the 10mmol/L epidermal growth factor aqueous solution, be 4 ℃ in temperature and stirred 72 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains the hollow silica ball with kernel of load table skin growth factor.
With the hollow silica ball ultra-sonic dispersion with kernel of the load table skin growth factor that obtains in mass concentration is 0.1% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel of load table skin growth factor is 100mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of epidermal growth factor and the composite balls that gelatin is formed.The particle diameter of composite balls is 1000 μ m.
3. the 1g amino polyvinyl alcohol is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 100ml/h, applies voltage 50kV and carries out the electrospinning silk.On the receptor at 85cm place above the spinning nozzle, obtain the amino polyvinyl alcohol fiber.The about 300nm of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of epidermal growth factor and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded epidermal growth factor is 100mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 10
-3Mol/L, mix homogeneously, room temperature was fully reacted 60 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the amino polyvinyl alcohol fiber of human tissue engineering support base material.The composite balls 100mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the amino polyvinyl alcohol fiber that step 3 prepares that concentration is 100mg/ml, 4 ℃ were reacted 4 hours down, take out the amino polyvinyl alcohol fiber after soaking, wash about 3 times with phosphate buffer, but obtain the amino polyvinyl alcohol fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded the slow release epidermal growth factor.
When this human tissue engineering support can sustain damage at people's blood vessel, when blood vessel is repaired, its recovery support as blood vessel is used.
Embodiment 3.
1.0.1g (particle diameter is 700nm, and outer casing thickness is 50nm, and mesoporous aperture is 20nm, and specific surface area is 1000m to have the hollow silica sub-micron ball of kernel (kernel size for 250nm)
2/ g) be immersed in the 0.1mmol/L bone morphogenetic protein aqueous solution, be 4 ℃ in temperature and stirred 48 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of bone morphogenetic protein.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading bone morphogenetic protein that will obtain is in mass concentration is 9.8% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads bone morphogenetic protein is 1mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of bone morphogenetic protein and the composite balls that gelatin is formed.The particle diameter of composite balls is 180 μ m.
3. the 0.2g gelatin is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 1ml/h, applies voltage 5kV and carries out the electrospinning silk.On the receptor at 0.1cm place above the spinning nozzle, obtain gelatin fiber.About 40 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of bone morphogenetic protein and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded bone morphogenetic protein is 0.05mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 5 * 10
-6Mol/L, mix homogeneously, room temperature was fully reacted 30 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the gelatin fiber of human tissue engineering support base material.The composite balls 0.05mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the gelatin fiber that step 3 prepares that concentration is 0.05mg/ml, 4 ℃ were reacted 24 hours down, take out the gelatin fiber after soaking, wash about 3 times with phosphate buffer, but obtain the gelatin fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded the slow release bone morphogenetic protein.
When this human tissue engineering support can sustain damage at people's cartilage, when cartilage is repaired, its recovery support as cartilage is used.
Embodiment 4.
1.1g (particle diameter is 500nm, and outer casing thickness is 50nm, and mesoporous aperture is 45nm, and specific surface area is 650m to have the hollow silica sub-micron ball of kernel (kernel size for 230nm)
2/ g) be immersed in the 1mmol/L hepatocyte growth factor aqueous solution, be 4 ℃ in temperature and stirred 50 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of hepatocyte growth factor.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading hepatocyte growth factor that will obtain is in mass concentration is 5% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads hepatocyte growth factor is 10mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of hepatocyte growth factor and the composite balls that gelatin is formed.The particle diameter of composite balls is 50 μ m.
3. the 1g fibroin is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 10ml/h, applies voltage 15kV and carries out the electrospinning silk.On the receptor at 10cm place above the spinning nozzle, obtain fibroin fiber.About 90 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of hepatocyte growth factor and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded hepatocyte growth factor is 0.01mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 10
-5Mol/L, mix homogeneously, room temperature was fully reacted 30 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the fibroin fiber of human tissue engineering support base material.The composite balls 0.01mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the fibroin fiber that step 3 prepares that concentration is 0.01mg/ml, 4 ℃ were reacted 48 hours down, take out the fibroin fiber after soaking, wash about 3 times with phosphate buffer, but obtain the fibroin fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded the slow release hepatocyte growth factor.
When this human tissue engineering support can sustain damage at people's liver, when liver is repaired, its recovery support as liver is used.
Embodiment 5.
1.0.01g (particle diameter is 700nm, and outer casing thickness is 40nm, and mesoporous aperture is 25nm, and specific surface area is 800m to have the hollow silica sub-micron ball of kernel (kernel size for 250nm)
2/ g) be immersed in the 5mmol/L hepatocyte growth factor aqueous solution, be 4 ℃ in temperature and stirred 12 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of hepatocyte growth factor.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading hepatocyte growth factor that will obtain is in mass concentration is 2% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads hepatocyte growth factor is 0.1mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of hepatocyte growth factor and the composite balls that gelatin is formed.The particle diameter of composite balls is 160 μ m.
3. the 0.5g polylactic acid is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 0.1ml/h, applies voltage 10kV and carries out the electrospinning silk.On the receptor at 20cm place above the spinning nozzle, obtain acid fiber by polylactic.About 100 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of hepatocyte growth factor and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded hepatocyte growth factor is 10mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 10
-5Mol/L, mix homogeneously, room temperature was fully reacted 45 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the acid fiber by polylactic of human tissue engineering support base material.The composite balls 10mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the acid fiber by polylactic that step 3 prepares that concentration is 10mg/ml, 4 ℃ were reacted 24 hours down, take out the acid fiber by polylactic after soaking, wash about 3 times with phosphate buffer, but obtain the acid fiber by polylactic human tissue engineering support that load has the hollow silica ball with kernel that has loaded the slow release hepatocyte growth factor.
When this human tissue engineering support can sustain damage at people's liver, when liver is repaired, its recovery support as liver is used.
Embodiment 6.
1.0.5g (particle diameter is 220nm, and outer casing thickness is 40nm, and mesoporous aperture is 25nm, and specific surface area is 800m to have the hollow silica sub-micron ball of kernel (kernel size for 80nm)
2/ g) be immersed in the 1mmol/L transforming growth factor aqueous solution, be 4 ℃ in temperature and stirred 36 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of transforming growth factor.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading transforming growth factor that will obtain is in mass concentration is 0.05% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads transforming growth factor is 0.05mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of transforming growth factor and the composite balls that gelatin is formed.The particle diameter of composite balls is 250 μ m.
With the 0.5g starch dissolution in 10ml water, make electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 0.5ml/h, applies voltage 20kV and carries out the electrospinning silk.On the receptor at 5cm place above the spinning nozzle, obtain starch fiber.About 460 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of transforming growth factor and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded the transforming growth factor factor is 1mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 5 * 10
-5Mol/L, mix homogeneously, room temperature was fully reacted 50 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the starch fiber of human tissue engineering support base material.The composite balls 1mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the starch fiber that step 3 prepares that concentration is 1mg/ml, 4 ℃ were reacted 50 hours down, take out the starch fiber after soaking, wash about 3 times with phosphate buffer, but obtain the starch fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded the slow release transforming growth factor.
When this human tissue engineering support can sustain damage at people's kidney, when kidney is repaired, its recovery support as kidney is used.
Embodiment 7.
1.0.2g (particle diameter is 600nm, and outer casing thickness is 30nm, and mesoporous aperture is 50nm, and specific surface area is 600m to have the hollow silica sub-micron ball of kernel (kernel size for 200nm)
2/ g) be immersed in the 1mmol/L platelet derivation somatomedin aqueous solution, be 4 ℃ in temperature and stirred 60 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of platelet derivation somatomedin.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading platelet derivation somatomedin that will obtain is in mass concentration is 0.5% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads platelet derivation somatomedin is 0.2mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of platelet derivation somatomedin and the composite balls that gelatin is formed.The particle diameter of composite balls is 150 μ m.
With the 1g collagenolysis in 10ml water, make electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 10ml/h, applies voltage 30kV and carries out the electrospinning silk.On the receptor at 55cm place above the spinning nozzle, obtain collagen fiber.About 180 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of platelet derivation somatomedin and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded platelet derivation somatomedin is 0.2mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 2 * 10
-4Mol/L, mix homogeneously, room temperature was fully reacted 30 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the collagen fiber of human tissue engineering support base material.The composite balls 0.2mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the collagen fiber that step 3 prepares that concentration is 0.2mg/ml, 4 ℃ were reacted 48 hours down, take out the collagen fiber after soaking, wash about 3 times with phosphate buffer, but obtain the collagen fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded slow release platelet derivation somatomedin.
When this human tissue engineering support can sustain damage at people's skin, when skin is repaired, its recovery support as skin is used.
Embodiment 8.
1.0.05g (particle diameter is 300nm, and outer casing thickness is 30nm, and mesoporous aperture is 20nm, and specific surface area is 850m to have the hollow silica sub-micron ball of kernel (kernel size for 100nm)
2/ g) be immersed in the 0.1mmol/L cartilage regulin aqueous solution, be 4 ℃ in temperature and stirred 40 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains loading the hollow silica ball with kernel of cartilage regulin.
2. the hollow silica ball ultra-sonic dispersion with kernel of the loading cartilage regulin that will obtain is in mass concentration is 1% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel that loads the cartilage regulin is 0.02mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of cartilage regulin and the composite balls that gelatin is formed.The particle diameter of composite balls is 40 μ m.
3. the poly-ethanolamine of 1g is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 1ml/h, applies voltage 15kV and carries out the electrospinning silk.On the receptor at 20cm place above the spinning nozzle, obtain poly-ethanolamine fiber.About 100 microns of average fibre diameter.
The loading that step 2 is obtained the composite balls formed of the hollow silica ball with kernel of cartilage regulin and gelatin be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded the cartilage regulin is 0.05mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 1 * 10
-4Mol/L, mix homogeneously, room temperature was fully reacted 20 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of amino covalence on the poly-ethanolamine fiber of human tissue engineering support base material.The composite balls 0.05mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the poly-ethanolamine fiber that step 3 prepares that concentration is 0.05mg/ml, 4 ℃ were reacted 40 hours down, take out the poly-ethanolamine fiber after soaking, wash about 3 times with phosphate buffer, but obtain the poly-ethanolamine fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded slow release cartilage regulin.
When this human tissue engineering support can sustain damage at people's cartilage, when skin is repaired, its recovery support as cartilage is used.
Embodiment 9
1.0.4g (particle diameter is 260nm, and outer casing thickness is 30nm, and mesoporous aperture is 10nm, and specific surface area is 600m to have the hollow silica sub-micron ball of kernel (kernel size for 90nm)
2/ g) be immersed in (L-glutaminate that contains 0.01mol/L) in the 0.01mmol/L epidermal growth factor aqueous solution, be 4 ℃ in temperature and stirred 52 hours down.Temperature is 4 ℃ down centrifugal, 3 times gained solid products of washed with de-ionized water, lyophilization obtains the hollow silica ball with kernel of load table skin growth factor and L-glutaminate.
With the hollow silica ball ultra-sonic dispersion with kernel of the load table skin growth factor that obtains and L-glutaminate in mass concentration is 0.5% aqueous gelatin solution, the final concentration of hollow silica ball in aqueous gelatin solution with kernel of load table skin growth factor and L-glutaminate is 0.2mg/mL, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of epidermal growth factor and L-glutaminate and the composite balls that gelatin is formed.The particle diameter of composite balls is 15 μ m.
3. the 1g polylysine is dissolved in the 10ml water, makes electric spinning liquid.The spinning liquid that is disposed is joined in the reservoir of electric spinning device, adopt No. 9 the tack spinning head, the spinning liquid flow velocity is 0.5ml/h, applies voltage 5kV and carries out the electrospinning silk.On the receptor at 15cm place above the spinning nozzle, obtain the polylysine fiber.About 600 microns of average fibre diameter.
The loading that step 2 is obtained the hollow silica ball with kernel of epidermal growth factor and L-glutaminate and the composite balls that gelatin is formed be dispersed in the alcohol solvent, the hollow silica sub-micron ball with kernel that has loaded epidermal growth factor and L-glutaminate is 0.4mg/mL with the concentration of composite balls in alcohol solvent of gelatin composition; Add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, make N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in above-mentioned alcohol solvent be respectively 1 * 10
-3Mol/L, mix homogeneously, room temperature was fully reacted 30 minutes, washed 2 times with phosphate buffer afterwards, obtain on the surface of composite balls can with as the link coupled activated carboxylic group of the amino covalence on the collagen of human tissue engineering support base material.The composite balls 0.4mg/ml of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid that passes through the polylysine fiber that step 3 prepares that concentration is 0.4mg/ml, 4 ℃ were reacted 24 hours down, take out the polylysine after soaking, wash about 3 times with phosphate buffer, but obtain the polylysine fiber human tissue engineering support that load has the hollow silica ball with kernel that has loaded slow release epidermal growth factor and L-glutaminate.
When this human tissue engineering support can sustain damage at people's skin, when skin is repaired, its recovery support as skin is used.
Claims (19)
- A load human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, be that hollow silica sub-micron ball with kernel by having loaded cell growth factor and gelatin self assembly are to have loaded the composite balls that the hollow silica sub-micron ball with kernel of cell growth factor and gelatin are formed, it loaded on the high molecular polymer fiber base material for preparing by electrical spinning method then and obtain; It is characterized in that:On as the high molecular polymerization fibres of human tissue engineering support base material load the hollow silica sub-micron ball with kernel of controlled-release cell growth factor and the composite balls that gelatin is formed.
- Load according to claim 1 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: described have in the hollow silica sub-micron ball of kernel and the composite balls that gelatin is formed also loaded nutrient substance.
- Load according to claim 1 and 2 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: described have the hollow silica sub-micron ball of kernel and the particle diameter of the composite balls that gelatin is formed is 1 μ m～1000 μ m.
- Load according to claim 1 and 2 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: the particle diameter of described hollow silica sub-micron ball with kernel is between 100～1000nm, and outer casing thickness is between 20～200nm; It is the movably preparing spherical SiO 2 kernel of 50～500nm that one particle diameter is arranged in the cavity of this hollow silica sub-micron ball; This hollow silica sub-micron ball has meso-hole structure, and mesoporous aperture is 3～50nm; The specific surface area of this hollow silica sub-micron ball is 100～1000m 2/ g.
- Load according to claim 3 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: the particle diameter of described hollow silica sub-micron ball with kernel is between 100～1000nm, and outer casing thickness is between 20～200nm; It is the movably preparing spherical SiO 2 kernel of 50～500nm that one particle diameter is arranged in the cavity of this hollow silica sub-micron ball; This hollow silica sub-micron ball has meso-hole structure, and mesoporous aperture is 3～50nm; The specific surface area of this hollow silica sub-micron ball is 100～1000m 2/ g.
- Load according to claim 1 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: described cell growth factor is selected from transforming growth factor, epidermal growth factor, VEGF, basic fibroblast growth factor, nerve growth factor, the cartilage regulin, glial growth factor, platelet derivation somatomedin, hepatocyte growth factor, people's epithelial cells somatomedin, insulin like growth factor, a kind of in the bone morphogenetic protein or greater than more than one.
- Load according to claim 2 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: described nutrient substance is selected from vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, tryptophan, threonine, methionine, valine, lysine, leucine, isoleucine, phenylalanine, L-glutaminate, purine, pyrimidine, glucose, fructose, galactose, lactose, sucrose, maltose, cholic acid, choline, sterin, creatine, prostaglandin, epinephrine, insulin, cholesterol, phospholipid, glycolipid, hemoglobin, ribose, a kind of in the deoxyribose or greater than more than one.
- Load according to claim 1 the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: the diameter of described high molecular polymerization fibres as the human tissue engineering support base material is 10nm～1000 μ m.
- According to claim 1 or 8 described loads the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: described high molecular polymer is an amino polyvinyl alcohol, hold amino polylactic acid, hold the statistic copolymer of amino lactide and Acetic acid, hydroxy-, bimol. cyclic ester, hold the random or block copolymer of amino lactide-ethylene glycol-Acetic acid, hydroxy-, bimol. cyclic ester, polymine, the polypropylene imines, polyethyene diamine, polyamide, poly-ethanolamine, hold amino Polyethylene Glycol, polylysine, poly-gamma-glutamic acid, poly-aspartate, poly arginine, poly-asparagine, chitin, chitosan, poly-amino-beta--cyclodextrin, gelatin, collagen, aminoglycan, fibroin, spider silk fibroin, aminocellulose or amino starch.
- One kind according to each described load of claim 1～9 preparation method of human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that this method may further comprise the steps:1) the hollow silica sub-micron ball that will have a kernel is immersed in the cell growth factor aqueous solution, being 4 ℃ in temperature stirs down, be centrifugal under 4 ℃ in temperature then, with washed with de-ionized water gained solid product, lyophilization has obtained loading the hollow silica sub-micron ball with kernel of cell growth factor;2) loading that step 1) is obtained the hollow silica sub-micron ball ultra-sonic dispersion with kernel of cell growth factor in aqueous gelatin solution, lyophilization has then obtained loading the hollow silica sub-micron ball with kernel of cell growth factor and the composite balls that gelatin is formed;3) with step 2) loading that obtains the hollow silica sub-micron ball with kernel of cell growth factor and the composite balls that gelatin is formed be dispersed in the alcohol solvent, add N-hydroxy-succinamide and 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimides, mix homogeneously, fully reaction under the room temperature, afterwards with phosphate buffer washing, obtain on the surface of composite balls with as the link coupled activated carboxylic group of the amino covalence on the high molecular polymer of human tissue engineering support base material; The composite balls of the activated carboxylic that obtains is distributed to contains in the phosphate-buffered dispersion liquid for preparing by electrical spinning method as the high molecular polymerization fibres of human tissue engineering support base material, 4 ℃ of reactions down, take out the high molecular polymerization fibres after soaking, with phosphate buffer washing, the human tissue engineering support of hollow silica sub-micron ball of controlled-release cell growth factor that obtained load with kernel.
- 11. method according to claim 10 is characterized in that: be in the step 1) with 10 -3It is 10 that the hollow silica sub-micron ball that～10g has a kernel is immersed in concentration -3In the cell growth factor aqueous solution of～10mmol/L.
- 12. according to claim 10 or 11 described methods, it is characterized in that: also contain nutrient substance in the cell growth factor aqueous solution.
- 13. method according to claim 10 is characterized in that: the final concentration of hollow silica sub-micron ball in aqueous gelatin solution with kernel that has loaded cell growth factor is 10 -3～100mg/mL.
- 14. method according to claim 12 is characterized in that: the final concentration of hollow silica sub-micron ball in aqueous gelatin solution with kernel that has loaded cell growth factor and nutrient substance is 10 -3～100mg/mL.
- 15. according to claim 13 or 14 described methods, it is characterized in that: the mass concentration of aqueous gelatin solution is 0.05～10%.
- 16. method according to claim 10 is characterized in that: having loaded the hollow silica sub-micron ball with kernel of cell growth factor and the concentration of composite balls in alcohol solvent of gelatin composition in the step 3) is 10 -2～10 2Mg/mL; N-hydroxy-succinamide and 1-ethyl-3-(3-the dimethyl aminopropyl)-concentration of carbodiimides in alcohol solvent is respectively 10 -7～10 -3Mol/L.
- 17. method according to claim 10 is characterized in that: contain in the phosphate-buffered dispersion liquid in the step 3) to pass through the high molecular polymerization fibres as the human tissue engineering support base material that electrical spinning method prepares be 10 -2～10 2Mg/ml.
- 18. one kind according to each described load of claim 1～9 purposes of human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel, it is characterized in that: described load the human tissue engineering support of hollow silica ball of controlled-release cell growth factor with kernel as the support of the reparation or the reconstruction of tissue or organ.
- 19. purposes according to claim 18 is characterized in that: described tissue or organ comprise liver, nerve, bone, cartilage, kidney, bladder, blood vessel, skin or heart.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008102240131A CN101721751B (en) | 2008-10-10 | 2008-10-10 | Human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and preparation method and applications thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008102240131A CN101721751B (en) | 2008-10-10 | 2008-10-10 | Human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and preparation method and applications thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101721751A true CN101721751A (en) | 2010-06-09 |
| CN101721751B CN101721751B (en) | 2013-01-02 |
Family
ID=42443691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008102240131A Expired - Fee Related CN101721751B (en) | 2008-10-10 | 2008-10-10 | Human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and preparation method and applications thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101721751B (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953797A (en) * | 2010-09-06 | 2011-01-26 | 中华人民共和国卫生部肝胆肠外科研究中心 | Method for preparing medicament carrying controlled-release nanometer material and application |
| CN102091331A (en) * | 2011-01-19 | 2011-06-15 | 浙江大学 | Carboxyl mesoporous silica nanoparticle carrier material and preparation method thereof |
| CN102671244A (en) * | 2012-06-04 | 2012-09-19 | 广州迈普再生医学科技有限公司 | Micro/nano-fiber bone repairing scaffold and production method thereof |
| CN103990177A (en) * | 2014-04-29 | 2014-08-20 | 东华大学 | Preparation method for mesoporous-silicon medicine-carrying system modified by bone-morphogenetic-protein active polypeptide |
| CN105288749A (en) * | 2015-05-20 | 2016-02-03 | 北京航空航天大学 | Preparation method of slow-release polypeptide growth factor biological material scaffold |
| CN106344966A (en) * | 2015-07-13 | 2017-01-25 | 中南大学 | Method for improving cell adhesion of polyglycolic acid stent by using mesoporous silica |
| CN106706524A (en) * | 2017-02-22 | 2017-05-24 | 大连大学 | Method of quickly detecting oxygen content in gas by using fibroin membrane |
| CN106806939A (en) * | 2017-03-29 | 2017-06-09 | 中国人民解放军国防科学技术大学 | Bone renovating material and its preparation method and application |
| CN109754394A (en) * | 2018-12-28 | 2019-05-14 | 上海联影智能医疗科技有限公司 | 3 d medical images processing unit and method |
| CN109825194A (en) * | 2019-01-24 | 2019-05-31 | 首都医科大学宣武医院 | A kind of heat-proof coating material of medical catheter and the preparation method and application thereof |
| CN113750294A (en) * | 2021-08-31 | 2021-12-07 | 四川大学 | Nerve repair stent loaded with multiple gene vector microspheres and preparation method thereof |
| US11341734B2 (en) | 2018-12-17 | 2022-05-24 | Shanghai United Imaging Intelligence Co., Ltd. | Systems and methods for image segmentation |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0301130A3 (en) * | 2000-01-28 | 2006-07-28 | Smithkline Beecham Corp | Electrospun pharmaceutical compositions |
| TW200410714A (en) * | 2002-08-07 | 2004-07-01 | Smithkline Beecham Corp | Electrospun amorphous pharmaceutical compositions |
| CN1181892C (en) * | 2002-08-14 | 2004-12-29 | 苏州大学 | Porous material for scaffold of tissue engineering and its preparing process |
| CN1442133A (en) * | 2003-04-17 | 2003-09-17 | 中国科学院长春应用化学研究所 | Ultrafine fiber medicine dosage form and its preparation method |
| CN101121519B (en) * | 2006-08-08 | 2012-03-28 | 中国科学院理化技术研究所 | Hollow silicon dioxide sub-micron sphere with inner core and its preparation method and use |
| CN100396340C (en) * | 2006-09-05 | 2008-06-25 | 四川大学 | Composite nanometer hydroxy apatitel medical polymer material tissue engineering stent material and preparation method |
-
2008
- 2008-10-10 CN CN2008102240131A patent/CN101721751B/en not_active Expired - Fee Related
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953797A (en) * | 2010-09-06 | 2011-01-26 | 中华人民共和国卫生部肝胆肠外科研究中心 | Method for preparing medicament carrying controlled-release nanometer material and application |
| CN101953797B (en) * | 2010-09-06 | 2012-05-23 | 中华人民共和国卫生部肝胆肠外科研究中心 | Method for preparing medicament carrying controlled-release nanometer material and application |
| CN102091331A (en) * | 2011-01-19 | 2011-06-15 | 浙江大学 | Carboxyl mesoporous silica nanoparticle carrier material and preparation method thereof |
| CN102091331B (en) * | 2011-01-19 | 2012-11-21 | 浙江大学 | Carboxyl mesoporous silica nanoparticle carrier material and preparation method thereof |
| CN102671244A (en) * | 2012-06-04 | 2012-09-19 | 广州迈普再生医学科技有限公司 | Micro/nano-fiber bone repairing scaffold and production method thereof |
| CN102671244B (en) * | 2012-06-04 | 2015-01-21 | 广州迈普再生医学科技有限公司 | Micro/nano-fiber bone repairing scaffold and production method thereof |
| CN103990177A (en) * | 2014-04-29 | 2014-08-20 | 东华大学 | Preparation method for mesoporous-silicon medicine-carrying system modified by bone-morphogenetic-protein active polypeptide |
| CN105288749A (en) * | 2015-05-20 | 2016-02-03 | 北京航空航天大学 | Preparation method of slow-release polypeptide growth factor biological material scaffold |
| CN106344966A (en) * | 2015-07-13 | 2017-01-25 | 中南大学 | Method for improving cell adhesion of polyglycolic acid stent by using mesoporous silica |
| CN106706524A (en) * | 2017-02-22 | 2017-05-24 | 大连大学 | Method of quickly detecting oxygen content in gas by using fibroin membrane |
| CN106706524B (en) * | 2017-02-22 | 2019-04-19 | 大连大学 | A method of using oxygen content in the quick detection gas of fibroin film |
| CN106806939A (en) * | 2017-03-29 | 2017-06-09 | 中国人民解放军国防科学技术大学 | Bone renovating material and its preparation method and application |
| CN106806939B (en) * | 2017-03-29 | 2020-03-31 | 中国人民解放军国防科学技术大学 | Bone repair material and preparation method and application thereof |
| US11341734B2 (en) | 2018-12-17 | 2022-05-24 | Shanghai United Imaging Intelligence Co., Ltd. | Systems and methods for image segmentation |
| US11836925B2 (en) | 2018-12-17 | 2023-12-05 | Shanghai United Imaging Intelligence Co., Ltd. | Systems and methods for image segmentation |
| CN109754394A (en) * | 2018-12-28 | 2019-05-14 | 上海联影智能医疗科技有限公司 | 3 d medical images processing unit and method |
| CN109825194A (en) * | 2019-01-24 | 2019-05-31 | 首都医科大学宣武医院 | A kind of heat-proof coating material of medical catheter and the preparation method and application thereof |
| CN113750294A (en) * | 2021-08-31 | 2021-12-07 | 四川大学 | Nerve repair stent loaded with multiple gene vector microspheres and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101721751B (en) | 2013-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101721751B (en) | Human tissue engineering support loaded with controlled-release cell growth factor and provided with hollow silicon dioxide ball with kernel and preparation method and applications thereof | |
| Wu et al. | Resorbable polymer electrospun nanofibers: History, shapes and application for tissue engineering | |
| Gorain et al. | The use of nanoscaffolds and dendrimers in tissue engineering | |
| Ahmad et al. | Chitosan centered bionanocomposites for medical specialty and curative applications: a review | |
| Ghaee et al. | Biomimetic nanocomposite scaffolds based on surface modified PCL-nanofibers containing curcumin embedded in chitosan/gelatin for skin regeneration | |
| Asadi et al. | Common biocompatible polymeric materials for tissue engineering and regenerative medicine | |
| Bakhshandeh et al. | Tissue engineering; strategies, tissues, and biomaterials | |
| Dahlin et al. | Polymeric nanofibers in tissue engineering | |
| Liu et al. | Chitosan-based biomaterials for tissue repair and regeneration | |
| Toh et al. | Advances in hydrogel delivery systems for tissue regeneration | |
| Venugopal et al. | Interaction of cells and nanofiber scaffolds in tissue engineering | |
| Shi et al. | Therapeutic potential of chitosan and its derivatives in regenerative medicine | |
| US9925301B2 (en) | Methods of producing and using silk microfibers | |
| Ayres et al. | Nanotechnology in the design of soft tissue scaffolds: innovations in structure and function | |
| He et al. | Current advances in microsphere based cell culture and tissue engineering | |
| CN100421736C (en) | A gradient laminated composite supporting frame material based on bionic structures and its preparation method | |
| US9192655B2 (en) | System and method for a hydrogel and hydrogel composite for cartilage repair applications | |
| Maleki et al. | Nanofiber-based systems intended for diabetes | |
| Zhu et al. | Advanced injectable hydrogels for cartilage tissue engineering | |
| Rodriguez-Velazquez et al. | Polysaccharide-based nanobiomaterials as controlled release systems for tissue engineering applications | |
| Yang et al. | The application of natural polymer–based hydrogels in tissue engineering | |
| Yang et al. | Cell membrane-biomimetic coating via click-mediated liposome fusion for mitigating the foreign-body reaction | |
| Yuvarani et al. | Chitosan modified alginate-polyurethane scaffold for skeletal muscle tissue engineering | |
| de Lima et al. | Electrospinning of hydrogels for biomedical applications | |
| Deng et al. | Application of decellularized scaffold combined with loaded nanoparticles for heart valve tissue engineering in vitro |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130102 Termination date: 20151010 |
|
| EXPY | Termination of patent right or utility model |