CN104523356A - Intervertebral disc imitating spine fuser and preparing method thereof - Google Patents
Intervertebral disc imitating spine fuser and preparing method thereof Download PDFInfo
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- CN104523356A CN104523356A CN201410838729.6A CN201410838729A CN104523356A CN 104523356 A CN104523356 A CN 104523356A CN 201410838729 A CN201410838729 A CN 201410838729A CN 104523356 A CN104523356 A CN 104523356A
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Abstract
The invention discloses an intervertebral disc imitating spine fuser and a preparing method thereof. An inner cylinder of an annular cylindrical support is filled with a core layer. Locating blind holes are formed in the upper surface and the lower surface of the annular cylindrical support. A magnesium wire is embedded on the outer periphery of the annular cylindrical support. The annular cylindrical support is made of chitosan with the porosity of 0%-40%. The core layer is of a chitosan mult-hole structure with the hole diameter of 50-500 microns and the porosity of 60%-95%. Interferon, bone morphogenetic protein and nanometer hydroxyapatite composite are arranged on a hole wall of the multi-hole structure. The intervertebral disc imitating spine fuser is used as a fusion support in an intervertebral fusion operation, an autogenous bone and an allograft bone are of no need, bone fusion is induced quickly, the support can be degraded safely, and secondary operation is of no need.
Description
Technical field
The present invention relates to a kind of degradable with induced osteogenesis ability and imitate intervertebral disc spine cage and preparation method thereof.
Background technology
Clinical treatment lumbar disc disease, effective method is interbody fusion the most.I.e. Artificial Intervention supporting bracket, then places autologous bone or homogeneous allogenic bone in the bracket, and induction vertebra merges mutually.
Present stage Clinical practice Invasive lumbar fusion device without osteoinductive and degradability.Get autologous patient osteodynia bitterness very big, homogeneous allogenic bone acquiring way difficulty.Fusion device, without degradability, makes patient must bear secondary misery, and inflammation infection risk increases.
Researched and developed at present and had polylactic acid (PLA) with the Biodegradable scaffold material of clinical trial, hydroxyapatite (HA), magnesium metal, Poly(D,L-lactide-co-glycolide (PLGA), cellulose and chitosan (CS) several.Wherein PLA and PLGA support, catabolite lactic acid can cause inflammatory reaction in body.Hydroxyapatite is difficult to become support separately, and degradation in vivo speed is extremely slow.Magnesium metal support, degradation rate is difficult to control, and can cause structural failure after implantation because of fast erosion.Cellulose rack forming difficulty, degradation cycle is difficult to regulation and control.Chitosan is shrimp and crab shells modified product, and mechanical property is good, and biocompatibility is excellent, and degradation property controllable is safe and reliable.
Summary of the invention
The object of the invention is the deficiency for current Invasive lumbar fusion device technology, propose a kind of imitative intervertebral disc spine cage and preparation method thereof
Imitative intervertebral disc spine cage of the present invention comprises ring-shaped cylinder support, sandwich layer is full of in cylinder in ring-shaped cylinder support, there is Blind locating holes on the upper and lower surface of ring-shaped cylinder support respectively, annularly the excircle of cylindrical holder is embedded with magnesium silk, the chitosan of described ring-shaped cylinder support to be porosity be 0-40%, sandwich layer is that aperture is at 50-500 μm, porosity is the chitosan multi-porous structure of 60-95%, and the hole wall of loose structure has interferon, bone morphogenetic protein and nanometer hydroxyapatite complex.
The preparation method of imitative intervertebral disc spine cage of the present invention, comprises the steps:
1) be dissolved in the aqueous acetic acid of mass concentration 2%-5% by chitosan, the chitosan-acetic acid solution of preparation mass concentration 3%-10%, is filled with in ring mould, then after using the gelation of mass concentration 3%-10% sodium hydroxide, washing is dried, and obtains ring-shaped cylinder support;
2) chitosan is dissolved in the aqueous acetic acid of mass concentration 2%-5%, the chitosan-acetic acid solution of preparation mass concentration 1%-10%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of mass concentration 3%-10% sodium hydroxide again, washing, freezing at-20 DEG C to-60 DEG C, dry, obtaining porosity is 60-95%, the chitosan multi-porous structural core layer of aperture 50-500 μm;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 10-500ng/mL, the concentration of bone morphogenetic protein is 5-200ng/mL, the concentration of nanometer hydroxyapatite is 0.1-1g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this mixed dispersion liquid, lyophilizing;
4) at the upper and lower surface of ring-shaped cylinder support several diameters of uniform brill 4-6 mm respectively, the hole of degree of depth 1-2 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
Interferon described in the present invention can IFN-α, IFN-β or IFN-γ.Described bone morphogenetic protein can be BMP-2 or BMP-7.
Imitative intervertebral disc spine cage of the present invention has the three dimensional structure similar with people's spinal disc, and ring-shaped cylinder brace aperture rate is lower, has higher comprcssive strength and mechanical stability, can provide the support force in intervertebral fusion process.The Blind locating holes on upper and lower surface makes support stablize holding position after placement, does not move in intervertebral plane.Embed the magnesium silk of annular cylindrical holder, make support have development effect to X-ray in put procedure, facilitate operation technique, guarantee that stentplacement position is accurate.
The invention has the advantages that:
The Invasive lumbar fusion device with biomimetic features is providing outside support necessary in intervertebral agglutination, in vertebra, osteoblast under the induction of support inner core, can enter internal stent and attaches and breed, and then forms osseous tissue, rapid induction bone tissue restoration can regenerate, realize interbody bone and merge.Owing to not using autologous bone and homogeneous allogenic bone, considerably reduce operation painful, simplify operation process.After osseous tissue is formed, support can degradation in vivo, and patient takes out support without the need to accepting second operation, avoids misery, complication and inflammation probability are reduced greatly.Use this Invasive lumbar fusion device, patient's healing time after undergoing surgery can be made to reduce.Thus this Invasive lumbar fusion device has good Clinical practice effect.
Accompanying drawing explanation
Fig. 1 is imitative intervertebral disc spine cage schematic diagram.
Detailed description of the invention
The present invention is further illustrated below in conjunction with accompanying drawing and example.
Concentration described in embodiment all refers to mass concentration.
With reference to Fig. 1, imitative intervertebral disc spine cage of the present invention comprises ring-shaped cylinder support 3, sandwich layer 2 is full of in cylinder in ring-shaped cylinder support 3, the upper and lower surface of ring-shaped cylinder support 3 has Blind locating holes 1 respectively, annularly the excircle of cylindrical holder 3 is embedded with magnesium silk 4, the chitosan of described ring-shaped cylinder support 3 to be porositys be 0-40%, sandwich layer 2 is that aperture is at 50-500 μm, porosity is the chitosan multi-porous structure of 60-95%, and the hole wall of loose structure has interferon, bone morphogenetic protein and nanometer hydroxyapatite complex.
example 1
1) take 9 grams of Chitosan powder, join in 300 ml concn 2% aqueous acetic acids, mechanical agitation 2 hours, obtains the chitosan solution of transparent and homogeneous.Be poured in ring mould, be immersed in concentration 3% sodium hydrate aqueous solution after gelation in 2 hours, washing is dried, and obtains ring-shaped cylinder support;
2) taking 1g chitosan is dissolved in the aqueous acetic acid of 100g concentration 2%, the chitosan-acetic acid solution of compound concentration 1%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of concentration 3% sodium hydroxide again, washing,-20 DEG C of lyophilizations, obtaining porosity is 95%, the chitosan multi-porous structural core layer in 500 μm, aperture;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 10ng/mL, the concentration of bone morphogenetic protein is 5ng/mL, the concentration of nanometer hydroxyapatite is 0.1g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this mixed dispersion liquid, lyophilizing;
4) at upper and lower surface uniform brill 6 diameter 4 mm respectively of ring-shaped cylinder support, the hole of the degree of depth 1 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
example 2:
1) take 15 grams of Chitosan powder, join in 300 ml concn 3% aqueous acetic acids, mechanical agitation 2 hours, obtains the chitosan solution of transparent and homogeneous.Be poured in ring mould, be immersed in concentration 3% sodium hydrate aqueous solution after gelation in 2 hours, washing is dried, and obtains ring-shaped cylinder support;
2) taking 3g chitosan is dissolved in the aqueous acetic acid of 100g concentration 2%, the chitosan-acetic acid solution of preparation mass concentration 3%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of concentration 4% sodium hydroxide again, washing,-40 DEG C of lyophilizations, obtaining porosity is 90%, the chitosan multi-porous structural core layer in 350 μm, aperture;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 100ng/mL, the concentration of bone morphogenetic protein is 50ng/mL, the concentration of nanometer hydroxyapatite is 0.3g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this mixed dispersion liquid, lyophilizing;
4) uniform 6 diameter 4 mm that spud in respectively on the upper and lower surface of ring-shaped cylinder support, the hole of the degree of depth 1.5 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
example 3:
1) take 20 grams of Chitosan powder, join in 300 ml concn 4% aqueous acetic acids, mechanical agitation 2 hours, obtains the chitosan solution of transparent and homogeneous.Be poured in ring mould, be immersed in concentration 5% sodium hydrate aqueous solution after gelation in 2 hours, washing is dried, and obtains ring-shaped cylinder support;
2) taking 5g chitosan is dissolved in the aqueous acetic acid of 100g concentration 3%, the chitosan-acetic acid solution of compound concentration 5%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of concentration 5% sodium hydroxide again, washing, freezing at-40 DEG C, dry, obtaining porosity is 85%, the chitosan multi-porous structural core layer in 270 μm, aperture;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 300ng/mL, the concentration of bone morphogenetic protein is 100ng/mL, the concentration of nanometer hydroxyapatite is 0.5g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this dispersion liquid, lyophilizing;
4) uniform 6 diameter 5 mm that spud in respectively on the upper and lower surface of ring-shaped cylinder support, the hole of the degree of depth 1.5 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
example 4:
Take 25 grams of Chitosan powder, join in 300 ml concn 5% aqueous acetic acids, mechanical agitation 2 hours, obtains the chitosan solution of transparent and homogeneous.Be poured in ring mould, be immersed in concentration 8% sodium hydrate aqueous solution after gelation in 2 hours, washing is dried, and obtains ring-shaped cylinder support;
2) taking 8g chitosan is dissolved in the aqueous acetic acid of 100g concentration 5%, the chitosan-acetic acid solution of compound concentration 8%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of concentration 8% sodium hydroxide again, washing, freezing at-60 DEG C, dry, obtaining porosity is 70%, the chitosan multi-porous structural core layer in 100 μm, aperture;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 400ng/mL, the concentration of bone morphogenetic protein is 180ng/mL, the concentration of nanometer hydroxyapatite is 0.7g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this mixed dispersion liquid, lyophilizing;
4) uniform 4 diameter 5 mm that spud in respectively on the upper and lower surface of ring-shaped cylinder support, the hole of the degree of depth 2 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
example 5:
1) take 30 grams of Chitosan powder, join in 300 ml concn 5% aqueous acetic acids, mechanical agitation 2 hours, obtains the chitosan solution of transparent and homogeneous.Be poured in ring mould, be immersed in concentration 10% sodium hydrate aqueous solution after gelation in 2 hours, washing is dried, and obtains ring-shaped cylinder support;
2) taking 10g chitosan is dissolved in the aqueous acetic acid of 100g concentration 5%, the chitosan-acetic acid solution of compound concentration 10%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of concentration 10% sodium hydroxide again, washing, freezing at-60 DEG C, dry, obtaining porosity is 60%, the chitosan multi-porous structural core layer in 50 μm, aperture;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 500ng/mL, the concentration of bone morphogenetic protein is 200ng/mL, the concentration of nanometer hydroxyapatite is 0.1g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this mixed dispersion liquid, lyophilizing;
4) uniform 6 diameter 6 mm that spud in respectively on the upper and lower surface of ring-shaped cylinder support, the hole of the degree of depth 2 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
Claims (2)
1. an imitative intervertebral disc spine cage, it is characterized in that comprising ring-shaped cylinder support (3), sandwich layer (2) is full of in the interior cylinder of ring-shaped cylinder support (3), ring-shaped cylinder support (3) upper, lower surface has Blind locating holes (1) respectively, annularly the excircle of cylindrical holder (3) is embedded with magnesium silk (4), the chitosan of described ring-shaped cylinder support (3) to be porosity be 0-40%, sandwich layer (2) is that aperture is at 50-500 μm, porosity is the chitosan multi-porous structure of 60-95%, the hole wall of loose structure has interferon, bone morphogenetic protein and nanometer hydroxyapatite complex.
2. the method for preparation imitative intervertebral disc spine cage as claimed in claim 1, is characterized in that comprising the steps:
1) be dissolved in the aqueous acetic acid of mass concentration 2%-5% by chitosan, the chitosan-acetic acid solution of preparation mass concentration 3%-10%, is filled with in ring mould, then after using the gelation of mass concentration 3%-10% sodium hydroxide, washing is dried, and obtains ring-shaped cylinder support;
2) chitosan is dissolved in the aqueous acetic acid of mass concentration 2%-5%, the chitosan-acetic acid solution of preparation mass concentration 1%-10%, be filled with in the interior cylinder of ring-shaped cylinder support, use the gelation of mass concentration 3%-10% sodium hydroxide again, washing, freezing at-20 DEG C to-60 DEG C, dry, obtaining porosity is 60-95%, the chitosan multi-porous structural core layer of aperture 50-500 μm;
3) interferon, bone morphogenetic protein are dissolved in PBS solution, add nanometer hydroxyapatite again, obtain mixed dispersion liquid, the concentration of interferon in mixed dispersion liquid is made to be 10-500ng/mL, the concentration of bone morphogenetic protein is 5-200ng/mL, the concentration of nanometer hydroxyapatite is 0.1-1g/mL, by step 2) obtained chitosan multi-porous structural core layer is soaked in 1h in this mixed dispersion liquid, lyophilizing;
4) at the upper and lower surface of ring-shaped cylinder support several diameters of uniform brill 4-6 mm respectively, the hole of degree of depth 1-2 mm, annularly the excircle of cylindrical holder offers the groove of wide 1mm, dark 1mm, embeds magnesium silk.
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Cited By (1)
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CN106913406A (en) * | 2015-12-25 | 2017-07-04 | 苏州微创脊柱创伤医疗科技有限公司 | A kind of spinal fusion device and preparation method thereof |
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US20080183292A1 (en) * | 2007-01-29 | 2008-07-31 | Warsaw Orthopedic, Inc. | Compliant intervertebral prosthetic devices employing composite elastic and textile structures |
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CN102293693A (en) * | 2011-06-01 | 2011-12-28 | 中国人民解放军第四军医大学 | Porous titanium alloy human cervical interbody fusion cage with bioactivity and preparation method thereof |
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