CN104984394B - The preparation method of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating - Google Patents
The preparation method of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating Download PDFInfo
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Abstract
The preparation method of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating disclosed by the invention, including preparing calcic, phosphorus, collagen, the electrolyte of chitosan quaternary ammonium salt, using platinized platinum as to electrode, the metal substrate cleaned using acid is used as working electrode, electrochemical deposition is carried out using many potential step patterns, by adjusting the positive and negative of every section of step working electrode potential, size and every section of sedimentation time, without Multiple depositions, can quickly and easily realize that chitosan quaternary ammonium salt spatial distribution in substrate surface mineralized collagen coating is controllable, i.e. collagenic coating nexine enrichment chitosan quaternary ammonium salt and coating outer layer are enriched with chitosan quaternary ammonium salt.Using property of the chitosan quaternary ammonium salt with positive charge, Biological somatomedin is carried to collagenic coating different spatial, realize Biological somatomedin release behavior controllable adjustment, the ability that coating carries Biological somatomedin is increased simultaneously, and repairing field in hard bone tissue is with a wide range of applications.
Description
Technical field
The present invention relates to the preparation method of medical metal implant surfaces coating, especially medical metal implant surfaces
The preparation method of mineralized collagen coating.
Background technology
During Bone Defect Repari, internal own cells produce different growth factors to regulate and control Integrated implant mistake in different times
Journey is smoothed out, and the release behavior of growth factor usually determines whether Bone Defect Repari succeeds.Therefore, for novel metal implant material
Material, it should not only have preferable biocompatibility, should more have the bearing capacity of preferable growth factor or medicine and right
The release behaviors such as its growth factor for carrying have controllable ability.Typically one layer is coated with slow on metal implant surface
The organic substance embedded growth factor agent simultaneously of function is released to meet biocompatibility, growth therefore bearing capacity and release row
It is the requirement of control.But, coat one layer of organic matter coating with slow-release function to control growth factor release behavior, usually
Multistep, complicated preparation means are needed, its application in implant surfaces modification is limited.
At present, the method for organic coating is prepared on metallic matrix mainly electrochemical deposition method, spin-coating method and bionical heavy
Area method.Wherein, electrochemical deposition method has reaction condition gentle, the advantages of coating chemical composition and controllable thickness, in coating system
For being widely used for aspect.Chinese patent CN101545886B makes gold chloride in conducting polymer also using potential step method
Originally it was nano Au particle, and then fixed bio-sensing material and form composite sensitive film.But based on potential step method, using alternation
The research that potential deposition method regulates and controls distribution of the chitosan quaternary ammonium salt in collagenic coating has no report.Chitosan quaternary ammonium salt is wider
PH in the range of carry positive charge, its response to electric field is rapid, by using alternation potential deposition method, can regulate and control shitosan
The depositing behavior of quaternary ammonium salt, realizes that spatial distribution of the chitosan quaternary ammonium salt in collagenic coating is controllable, and then effectively control growth
The release behavior of the factor, it is significant for improving Bone Defect Repari speed and quality.
Collagen is one of main constituent in natural bone, and the signal that exposed functional group has in its molecule is passed
The effect of passing, thus with preferable biocompatibility.But collagen coating is limited to the bearing capacity of biotic factor etc..Have perhaps
Many researchs are devoted to improving bearing capacity, and such as Chinese patent CN103074659A is applied using constant potential electrodeposition process in mineralized collagen
Shitosan is introduced in layer, coating medicine, growth factor equivalent-load ability is improve.Chinese patent CN102028969A is using permanent
Current potential electrodeposition process is built with the fine and close chitosan layer of cause, porous mineralising chitosan layer and ore deposit successively from bottom to top in implant surfaces
Change collagen/chitosan crosslinked layer, improve the biology performance and drug carrying ability of coating.But according to mineralized collagen gravity pouring machine
Reason, can produce pH gradient near substrate in electrochemical deposition process, shitosan is depositing to the certain depth of coating with pH liters
Proton is lost after height, the shitosan for losing proton drastically declines to the response of electric field, it is impossible to which controllable adjustment shitosan is enriched in
The nexine or outer layer of mineralized collagen coating, limit control of the coating to growth factor equivalent-load locus, while losing
Coulomb force between the shitosan and growth factor of proton drastically declines so that bearing capacity of the whole coating to growth factor etc.
Improve limited.
The content of the invention
Carried it is an object of the invention to provide a kind of process is simple, with biological response high and the efficient growth factor
The system of ability and the controllable medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating of growth factor release behavior
Preparation Method.
The preparation method of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating of the invention, including with
Lower step：
1) chitosan quaternary ammonium salt is dissolved in distilled water, compound concentration is the chitosan quaternary ammonium saline solution of 0.5g/L, is put
It is stand-by in 4 DEG C；Type i collagen is dissolved in 0.005mol/L acetic acid, compound concentration is the collagen acetum of 0.5g/L, is placed in
4 DEG C stand-by；
2）Prepare electrolyte：Calcium containing compound is soluble in water, and it is containing for 10mmol/L ~ 100mmol/L to be configured to concentration
The calcium aqueous solution；Phosphorus-containing compound is soluble in water, it is configured to the phosphorous aqueous solution that concentration is 10mmol/L ~ 100mmol/L；To contain
The calcium aqueous solution and the phosphorous aqueous solution stirring mixing, solution A is obtained, by step 1) obtained in type i collagen acetum and shitosan
Quaternary ammonium salt aqueous solution mixes with solution A, calcium in mixed liquor, phosphorus, collagen, the quaternary ammonium root concentration of chitosan quaternary ammonium salt is respectively 4
~8mmol/L, 8~16 mmol/L, 0.3g/L, 0.32 ~ 0.016mmol/L, adjustment electrolyte ph are 4.3~4.6；
3) electrolyte is placed in the thermostat that temperature is 37 DEG C, using platinized platinum as to electrode, is crossed with sour cleaning treatment
Used as working electrode, distance is 1~2cm to metal substrate between two electrodes, and electrochemical deposition is carried out using many potential step patterns,
The positive voltage for applying on metallic substrates is 2.0~2.8V, and negative voltage is -1.5 ~ -2.5V, and step hop count is 3 ~ 7 sections, and every section is sunk
The product time is 1-20min, takes out metal substrate, stand-by after being cleaned with deionized water；
4) the biotic factor solution of 0.1 ~ 2 μ g/mL is prepared, the pH for adjusting biotic factor solution is 3 ~ 10, by what is 3) prepared
Metal substrate is immersed in biotic factor solution, is taken out after 1-3 days, in dry at 37 DEG C.
In the present invention, it is 20% ~ 99% that described chitosan quaternary ammonium salt is quaternary ammonium root substitution value, molecular mass is 1000 ~
100000 2- HACCs or quaternary ammonium root substitution value be 20% ~ 99%, molecular mass be 1000 ~
100000 N, N, N- trimethyl chitin quaternary ammonium salt.
In the present invention, described type i collagen is times water chestnut liquid type i collagen.
In the present invention, described biotic factor is that pH is 3 ~ 10 BMP-2, BMP-6 or BSA with negative electrical charge.
In the present invention, described calcium containing compound can be Ca (NO3)2·6H2O or CaCl2。
In the present invention, described phosphorus-containing compound can be NH4H2PO4Or NaH2PO4。
In the present invention, described metal substrate can be titanium plate, tantalum plate or magnesium plate.
The present invention carries out electrochemical deposition using many potential step patterns, realizes the Seedling height of medical metal implant surfaces
The factor is carried, the chitosan quaternary ammonium salt/collagen composite coating of cellular response high, by adjusting every section of step working electrode potential
Positive and negative, size and every section of sedimentation time, without Multiple depositions, can quickly and easily realize for chitosan quaternary ammonium salt being distributed to glue
Former coating different spaces, i.e. collagenic coating nexine are enriched with chitosan quaternary ammonium salt and collagenic coating outer layer enrichment chitosan quaternary ammonium salt.
Using property of the chitosan quaternary ammonium salt with positive charge, Biological somatomedin is carried to collagenic coating different spatial, it is real
Show Biological somatomedin release behavior controllable adjustment, while the ability that coating carries Biological somatomedin is increased, in os osseum
Tissue repair field is with a wide range of applications.
Brief description of the drawings
Fig. 1 is titanium implantses surface composite coating nexine enrichment 2- HACC patterns.
Fig. 2 is titanium implantses surface composite coating outer layer enrichment 2- HACC patterns.
Fig. 3 is that the nexine/outer layer of titanium implantses surface composite coating carries BMP-2 ability comparison diagrams.
Specific embodiment
The present invention is illustrated below in conjunction with instantiation：
Embodiment 1
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution；
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-1.5V(120s)、-2.4V(180s)、2V(60s)、-2.4V(480s)、2V(120s)、-
2.4V (720s), 2V (180s), take out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, dried in 37 DEG C of baking ovens, the 2- hydroxypropyls three that nexine is loaded with BMP-2 are obtained on titanium implantses surface
The composite coating of ammonio methacrylate shitosan/collagen, its pattern is shown in Fig. 1.Nexine refers to composite coating straight with titanium implantses surface
This side of contact.
Embodiment 2
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution.
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-2.4V(120s)、2V(60s)、-2.4V(360s)、2V(120s)、-2.4V(480s)、2V
(180s), -2.4V (480s), takes out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that outer layer is loaded with BMP-2 are obtained on titanium implantses surface
The composite coating of ammonium chloride shitosan/collagen, its pattern is shown in Fig. 2.Outer layer refers to composite coating non-straight with titanium implantses surface
This side of contact.
Embodiment 3
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.064mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution；
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-1.5V(120s)、-2.4V(180s)、2V(60s)、-2.4V(480s)、2V(120s)、-
2.4V (720s), 2V (180s), take out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, dried in 37 DEG C of baking ovens, the 2- hydroxypropyls three that nexine is loaded with BMP-2 are obtained on titanium implantses surface
The composite coating of ammonio methacrylate shitosan/collagen.
Embodiment 4
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.064mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution.
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-2.4V(120s)、2V(60s)、-2.4V(360s)、2V(120s)、-2.4V(480s)、2V
(180s), -2.4V (480s), takes out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that outer layer is loaded with BMP-2 are obtained on titanium implantses surface
The composite coating of ammonium chloride shitosan/collagen.
Embodiment 5
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.048mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution；
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-1.5V(120s)、-2.4V(180s)、2V(60s)、-2.4V(480s)、2V(120s)、-
2.4V (720s), 2V (180s), take out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, dried in 37 DEG C of baking ovens, the 2- hydroxypropyls three that nexine is loaded with BMP-2 are obtained on titanium implantses surface
The composite coating of ammonio methacrylate shitosan/collagen.
Embodiment 6
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.048mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution.
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-2.4V(120s)、2V(60s)、-2.4V(360s)、2V(120s)、-2.4V(480s)、2V
(180s), -2.4V (480s), takes out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that outer layer is loaded with BMP-2 are obtained on titanium implantses surface
The composite coating of ammonium chloride shitosan/collagen.
Comparing embodiment 1 arrives embodiment 6, and the nexine and outer layer of composite coating carry the contrast of BMP-2 abilities and see Fig. 3.
Embodiment 7
1) by quaternary ammonium root substitution value be 20%, molecular mass be 100000 2- HACCs it is molten
In distilled water, compound concentration is the chitosan quaternary ammonium saline solution of 0.5g/L, be placed in 4 DEG C it is stand-by；Times water chestnut liquid type i collagen is molten
Solution in 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By CaCl2It is soluble in water, it is configured to the Ca (NO that calcium concentration is 80mmol/L3)2The aqueous solution, will
NaH2PO4It is soluble in water, it is configured to the NaH for 80mmol/L containing phosphorus concentration2PO4The aqueous solution, by CaCl2The aqueous solution and NaH2PO4
Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- HACCs solution and A
Solution mix, make quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs concentration respectively 8mmol/L,
16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4. to adjust electrolyte ph with NaOH solution
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-2.4V(120s)、2V(60s)、-2.4V(360s)、2V(120s)、-2.4V(480s)、2V
(180s), -2.4V (480s), takes out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that outer layer is loaded with BMP-2 are obtained on titanium implantses surface
Ammonium chloride shitosan/collagen composite coating.
Embodiment 8
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 20mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 20mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 4mmol/L, 8 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.3 to adjust electrolyte ph with NaOH solution.
3) using the cleaned magnesium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to magnesium substrate
On voltage and time be respectively：-2.4V(120s)、2V(60s)、-2.4V(360s)、2V(120s)、-2.4V(480s)、2V
(180s), -2.4V (480s), takes out magnesium substrate after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the magnesium substrate of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that outer layer is loaded with BMP-2 are obtained in magnesium implant surfaces
Ammonium chloride shitosan/collagen composite coating.
Embodiment 9
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 100mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 100mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.016mmol/L, 0.3g/L, then it is 4.3 to adjust electrolyte ph with NaOH solution.
3) using the cleaned tantalum plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
2cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to tantalum substrate
On voltage and time be respectively：-2.4V(120s)、2V(60s)、-2.4V(360s)、2V(120s)、-2.4V(480s)、2V
(180s), -2.4V (480s), takes out tantalum substrate after deposition, standby after deionized water cleaning；
4) the BMP-6 solution of 2 μ g/mL is prepared, it is 3 to reconcile pH, the tantalum substrate of above-mentioned preparation is immersed in into 10mLBMP-6 molten
In liquid.Taken out after 1 day, in 37 DEG C of oven dryings, the 2- Hydroxyproyl Trimethyls that outer layer is loaded with BMP-6 are obtained in tantalum implant surfaces
Ammonium chloride shitosan/collagen composite coating.
Embodiment 10
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution.
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-2V(60s)、-2.5V(120s)、2.3V(120s)、-2.5V(480s)、2.3V(120s)、-
2.5V (720s), 2.3V (180s), take out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 10 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that nexine is loaded with BMP-2 are obtained on titanium implantses surface
Ammonium chloride shitosan/collagen composite coating.
Embodiment 11
1) it is 98% by quaternary ammonium root substitution value, molecular mass is that 30000 2- HACCs are dissolved in
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；Will times water chestnut liquid type i collagen dissolving
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2
The aqueous solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2Water
Solution and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, 2- hydroxypropyl-trimethyl ammonium chlorides
Chitosan solution mixes with solution A, makes the concentration of quaternary ammonium root and collagen in calcium, phosphorus, 2- HACCs
Respectively 8mmol/L, 16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4. to adjust electrolyte ph with NaOH solution
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：- 1.5V (240s), -2.4V (360s), 2V (180s), -2.4V (720s), 2V (180s), sink
Titanium-base is taken out after product, it is standby after deionized water cleaning；
4) the BSA solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mLBSA solution
In.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- Hydroxyproyl Trimethyl chlorinations that nexine is loaded with BSA are obtained on titanium implantses surface
Ammonium shitosan/collagen composite coating.
Embodiment 12
1) it is 98% by quaternary ammonium root substitution value, molecular mass is 30000 N, and N, N- trimethyl chitin quaternary ammonium salt are dissolved in steaming
Distilled water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；A times water chestnut liquid type i collagen is dissolved in
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
2) electrolyte is prepared：By CaCl2It is soluble in water, it is configured to the Ca (NO that calcium concentration is 60mmol/L3)2The aqueous solution, will
NH4H2PO4It is soluble in water, it is configured to the NH for 60mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by CaCl2The aqueous solution and
NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, N, N, N- trimethyl chitin quaternary ammonium salt are molten
Liquid mixes with solution A, makes calcium, phosphorus, N, and the concentration of quaternary ammonium root and collagen is respectively in N, N- trimethyl chitin quaternary ammonium salt
8mmol/L, 16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution.
3) using the cleaned titanium plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to titanium-base
On voltage and time be respectively：-1.5V(120s)、-2.4V(180s)、2V(60s)、-2.4V(480s)、2V(120s)、-
2.4V (720s), 2V (180s), take out titanium-base after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the titanium-base of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that nexine is loaded with BMP-2 are obtained on titanium implantses surface
Ammonium chloride shitosan/collagen composite coating.
Embodiment 13
It is 98% by quaternary ammonium root substitution value, molecular mass is 30000 N, and N, N- trimethyl chitin quaternary ammonium salt are dissolved in distillation
Water, compound concentration for 0.5g/L chitosan quaternary ammonium saline solution, be placed in 4 DEG C it is stand-by；A times water chestnut liquid type i collagen is dissolved in
In 0.005mol/L acetic acid, compound concentration for 0.5g/L collagen acetum, be placed in 4 DEG C it is stand-by；
Prepare electrolyte：By Ca (NO3)2·6H2O is soluble in water, is configured to the Ca (NO that calcium concentration is 80mmol/L3)2Water
Solution, by NH4H2PO4It is soluble in water, it is configured to the NH for 80mmol/L containing phosphorus concentration4H2PO4The aqueous solution, by Ca (NO3)2It is water-soluble
Liquid and NH4H2PO4Aqueous solution stirring mixing, obtains solution A.By times water chestnut liquid type i collagen, N, N, N- trimethyl chitin quaternary ammonium
Salting liquid mixes with solution A, makes calcium, phosphorus, N, and the concentration of quaternary ammonium root and collagen is respectively in N, N- trimethyl chitin quaternary ammonium salt
8mmol/L, 16 mmol/L, 0.08mmol/L, 0.3g/L, then it is 4.4 to adjust electrolyte ph with NaOH solution.
3) using the cleaned tantalum plate of surface acid as working electrode, used as to electrode, two electrode spacings are platinum electrode
1cm, takes 15ml electrolyte and is placed in 37 DEG C of thermostats, using many potential step electrochemical deposition patterns, is applied to tantalum substrate
On voltage and time be respectively：-1.5V(120s)、-2.4V(180s)、2V(60s)、-2.4V(480s)、2V(120s)、-
2.4V (720s), 2V (180s), take out tantalum substrate after deposition, standby after deionized water cleaning；
4) the BMP-2 solution of 2 μ g/mL is prepared, it is 7 to reconcile pH, and the tantalum substrate of above-mentioned preparation is immersed in into 10mL BMP-2
In solution.Taken out after 3 days, in 37 DEG C of oven dryings, the 2- hydroxypropyl trimethylammoniums that nexine is loaded with BMP-2 are obtained in tantalum implant surfaces
Ammonium chloride shitosan/collagen composite coating.
Claims (6)
1. the preparation method of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating, it is characterised in that including with
Lower step：
1) chitosan quaternary ammonium salt is dissolved in distilled water, compound concentration is the chitosan quaternary ammonium saline solution of 0.5g/L, is placed in 4 DEG C
It is stand-by；Type i collagen is dissolved in 0.005mol/L acetic acid, compound concentration is the collagen acetum of 0.5g/L, is placed in 4 DEG C and treats
With；
2）Prepare electrolyte：Calcium containing compound is soluble in water, it is configured to the calcic water that concentration is 10mmol/L ~ 100mmol/L
Solution；Phosphorus-containing compound is soluble in water, it is configured to the phosphorous aqueous solution that concentration is 10mmol/L ~ 100mmol/L；By calcic water
Solution and the phosphorous aqueous solution stirring mixing, solution A is obtained, by step 1) obtained in type i collagen acetum and chitosan quaternary ammonium
Saline solution mixes with solution A, make calcium in mixed liquor, phosphorus, collagen, the quaternary ammonium root concentration of chitosan quaternary ammonium salt be respectively 4~
8mmol/L, 8~16 mmol/L, 0.3g/L, 0.32 ~ 0.016mmol/L, adjustment electrolyte ph are 4.3~4.6；
3) electrolyte is placed in the thermostat that temperature is 37 DEG C, using platinized platinum as to electrode, with the metal that sour cleaning treatment is crossed
Used as working electrode, distance is 1~2cm to substrate between two electrodes, and electrochemical deposition is carried out using many potential step patterns, is applied
Positive voltage on metallic substrates is 2.0~2.8V, and negative voltage is -1.5 ~ -2.5V, and step hop count is 3 ~ 7 sections, during every section of deposition
Between be 1-20min, take out metal substrate, it is stand-by after being cleaned with deionized water；Described many its voltage changes of potential step pattern
Have：
- 1.5V, -2.4V, 2V, -2.4V, 2V, -2.4V, 2V, or -2.4V, 2V, -2.4V, 2V, -2.4V, 2V, -2.4V, or -
1.5V、-2.4V、2V、-2.4V、2V；
4) the biotic factor solution of 0.1 ~ 2 μ g/mL is prepared, the pH for adjusting biotic factor solution is 3 ~ 10, the metal that will 3) prepare
Substrate is immersed in biotic factor solution, is taken out after 1-3 days, in dry at 37 DEG C.
2. the preparation side of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating according to claim 1
Method, it is characterised in that described chitosan quaternary ammonium salt is that quaternary ammonium root substitution value is 20% ~ 99%, and molecular mass is 1000 ~ 100000
2- HACCs or quaternary ammonium root substitution value be 20% ~ 99%, molecular mass for 1000 ~ 100000 N,
N, N- trimethyl chitin quaternary ammonium salt.
3. the preparation side of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating according to claim 1
Method, it is characterised in that described type i collagen is times water chestnut liquid collagen.
4. the preparation side of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating according to claim 1
Method, it is characterised in that described biotic factor is that pH is 3 ~ 10 BMP-2, BMP-6 or BSA with negative electrical charge.
5. the preparation side of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating according to claim 1
Method, it is characterised in that described calcium containing compound is Ca (NO3)2·6H2O or CaCl2。
6. the preparation side of medical metal implant surfaces chitosan quaternary ammonium salt/collagen composite coating according to claim 1
Method, it is characterised in that described phosphorus-containing compound is NH4H2PO4Or NaH2PO4。
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| CN101156963A (en) * | 2007-11-08 | 2008-04-09 | 浙江大学 | Method for preparing similar bone bioactivity coatings medical material by galvano-chemistry method |
| CN103074659A (en) * | 2013-01-29 | 2013-05-01 | 浙江大学 | Preparation method of collagen coating embedded with chitosan microspheres on medical metal implant surface |
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| CN103074659A (en) * | 2013-01-29 | 2013-05-01 | 浙江大学 | Preparation method of collagen coating embedded with chitosan microspheres on medical metal implant surface |
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