CN107303397B - A kind of biologically active Injectable compound bone cement and its preparation method and application - Google Patents
A kind of biologically active Injectable compound bone cement and its preparation method and application Download PDFInfo
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- CN107303397B CN107303397B CN201610248345.8A CN201610248345A CN107303397B CN 107303397 B CN107303397 B CN 107303397B CN 201610248345 A CN201610248345 A CN 201610248345A CN 107303397 B CN107303397 B CN 107303397B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The present invention relates to a kind of biologically active Injectable compound bone cements and its preparation method and application.The bone cement is made of solid phase powder and solidify liquid two parts；Wherein, the solid phase powder is made of phosphosilicate bioactivity glass and calcium sulfate mixing, and chitosan and sodium β-glycerophosphate are contained in solidify liquid.Solid phase powder and solidify liquid are mixed according to a certain percentage, stirs evenly, forms composite bone cement after room temperature curing.Bone cement of the invention has good syringeability, anti-collapsibility and mechanical property.Simultaneously, bone cement of the invention has excellent bioactivity, biocompatibility and biological degradability, and the problem of being collapsed there is no calcium phosphate (CPC), calcium sulfate (CSC) bone cement later period, it can be grown for cell and necessary " bridge " is provided, it can be used in fractures, prepare the bio-medical material of filling material of bone and Bone Defect Repari, regeneration.
Description
Technical field
The invention belongs to biomedical material technology, it is related to a kind of bioactive bone cement and preparation method thereof and uses
On the way.
Background technique
As the aging trend of China human mortality increasingly aggravates, the incidence of osteoporosis centrum compression fracture (OVCF)
Increase year by year, has become one of the thorny problem in clinic.Percutaneous kyplasty (PKP) or minimally invasive centrum plasty
It (VP) is the main means for treating OVCF.Currently, common material has PMMA bone cement in PKP or VP
(PMMA), calcium phosphate bone cement (CPC) and calcium sulfate bone cement (CSC) etc., still, these materials are all lacked there is apparent
It falls into.
There are apparent heating problems in PMMA solidification process, and inject the hard solid non-degradable formed after centrum,
Inactive；Calorigenic effect of CPC with the CSC bone cement without similar PMMA has good biocompatibility, and can be degraded suction
It receives, however, this kind of material is easily defeated and dispersed, no bone-inducting active promotes bone tissue nucleus formation limited, and degradation rate and human body bone
Growth rate mismatches, and support prolonged enough cannot be provided when treating OVCF.For example, currently on the market applied to PKP'sBone cement (CSC and β-TCP composite bone cement), some patientss have apparent vertebral height to collapse during follow-up
It falls into, and the formation of its trabecular bone structure is slower.Therefore, seek one kind and have good bioactivity, bone tissue can be induced
It repairs, regeneration, and there is good anti-collapsibility and degradation rate appropriate, can be grown in new bone growth repair process for cell
The bone renovating material for providing long-time support enough, which has become, clinically to be compeled highly necessary to solve the problems, such as.
Phosphosilicate bioactivity glass (SPBG) is that one kind has good biological activity, degradable absorbability and biofacies
The bone renovating material of capacitive.In fluid environment, it can be formed on the surface of the material and hydroxy-apatite as bone tissue constituent class
Stone (HA), to make to form firm chemical bonding between bone tissue and material, induction new bone tissue is formed；In addition, it is precipitated
The adherency of Si, P, Ca ion pair osteocyte, proliferation and differentiation also have certain facilitation.It implants after a certain period of time,
SPBG can show excellent osteoinductive and osteogenic, provide the bon e formation interface for having biocompatibility, but also
The Osteogenic Stem that can dissociate for field of operation provides the bioactivity surface that can be colonized, and promotes the shape of new bone tissue
At.Currently, bio-vitricIt has been widely used for dentistry and plastic surgery etc. as filling or repair materials and faces
In bed treatment.
From the point of view of biology and chemical aspect, SPBG and calcium sulfate compound the two there are certain complementarity, will
It is possible that improving the osteoinductive of material, promotes bone tissue to be formed, solve the problems, such as that the absorbable material later period collapses.However, passing
Preparation method unite usually using half-H 2 O calcium sulphate as cured matrix, curing agent is done with water or physiological saline, by SPBG with the shape of filler
Formula introduces system.The content of SPBG in the system is very few, and the calcium sulfate itself as main body is degraded quickly, thus body
It is easy defeated and dispersed, the too fast problem of degradation rate, it is enough that this makes it be difficult to bone and its cells growth offer during Bone Defect Repari
Effective support of time.
Summary of the invention
The purpose of the present invention is to provide a kind of novel Injectable compound bone cement and preparation method thereof, the Composite Bone water
Mud has good syringeability, anti-collapsibility and a mechanical property, at the same also have excellent bioactivity, biocompatibility and
Biological degradability.
To achieve the above object, the present invention adopts the following technical scheme:
A kind of biologically active Injectable compound bone cement, is made of solid phase powder and solidify liquid two parts；Wherein,
The solid phase powder is made of phosphosilicate bioactivity glass and calcium sulfate mixing, and chitosan and β-glycerol are contained in solidify liquid
Sodium phosphate.
According to the present invention, the solid phase powder and the mass volume ratio (solid-to-liquid ratio) of solidify liquid are 1:1~3:1 (g/ml),
Preferably, it is 1.5:1~2:1 (g/ml).
According to the present invention, the sodium β-glycerophosphate is five water sodium β-glycerophosphates.
According to the present invention, the solid phase powder is grouped as by the group of following weight percent content:
Phosphosilicate bioactivity glass: greater than be equal to 20wt.% but be not 100wt.%, preferably 25wt.%~
99wt.%, also preferably 30wt.%~90wt.%；
Calcium sulfate: less than be equal to 80wt.% but be not 0wt.%, preferably 1wt.%~75wt.%, also preferably
10wt.%~70wt.%.
According to the present invention, the phosphosilicate bioactivity glass composition are as follows: x (SiO2)·y(CaO)·m(P2O5)·n
(Na2O), wherein x, y, m, n range (mol.%) are as follows: x be 45mol.%~80mol.%, y be 15mol.%~
40mol.%, m are 0mol.%~11mol.%, and n is 0mol.%~25mol.%.
According to the present invention, the calcium sulfate is α-half-H 2 O calcium sulphate, β-half-H 2 O calcium sulphate, calcium sulphate dihydrate, anhydrous slufuric acid
One of calcium etc. is a variety of.
According to the present invention, the mass percentage of chitosan is 1wt.%~5wt.%, β-glycerol phosphorus in the solidify liquid
The mass percentage of sour sodium (preferably five water sodium β-glycerophosphates) is 4wt.%~9wt.%.
According to the present invention, also containing aqueous acid is contained in the solidify liquid, specifically, the solidify liquid is by following quality
The group of percentage is grouped as:
Chitosan 1wt.%~5wt.%
Sodium β-glycerophosphate (preferably five water sodium β-glycerophosphates) 4wt.%~9wt.%
86wt.% containing aqueous acid~95wt.%.
According to the present invention, it is described containing aqueous acid be concentration be 0.1~1mol/L acetic acid aqueous solution, aqueous hydrochloric acid solution,
One of aqueous citric acid solution.
The preparation method of above-mentioned Injectable compound bone cement, it includes following steps:
(1) preparation of solid phase powder
Powder is made in phosphosilicate bioactive glass material；Calcium sulfate is spiked into the bioactivity glass powder
In, it is uniformly mixed, obtains solid phase powder；
(2) preparation of solidify liquid
Chitosan and sodium β-glycerophosphate in solidify liquid and the other components in solidify liquid are mixed to get the solidification
Liquid；
(3) preparation of composite bone cement
The solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1) is reconciled, the Composite Bone water is obtained
Mud.
According to the present invention, in step (1), the weight percent content of phosphosilicate bioactivity glass and calcium sulfate are as follows:
Phosphosilicate bioactivity glass: greater than be equal to 20wt.% but be not 100wt.%, preferably 25wt.%~
99wt.%, also preferably 30wt.%~90wt.%；
Calcium sulfate: less than be equal to 80wt.% but be not 0wt.%, preferably 1wt.%~75wt.%, also preferably
10wt.%~70wt.%.
According to the present invention, step (2) specifically: the solidify liquid is grouped as by the group of following mass percent: chitosan
1wt.%~5wt.%, sodium β-glycerophosphate (preferably five water sodium β-glycerophosphates) 4wt.%~9wt.%, and contain aqueous acid
86wt.%~95wt.%；It is matched according to above-mentioned solidify liquid, the chitosan for accounting for solidify liquid total amount 1wt.%~5wt.% is added
Containing in aqueous acid, being stirred to clear to get to chitosan aqueous solution；Then, solidify liquid total amount 4wt.% will be accounted for
The sodium β-glycerophosphate (preferably five water sodium β-glycerophosphates) of~9wt.% is dissolved in containing in aqueous acid, then under the action of stirring
It is instilled in the chitosan aqueous solution dropwise, the solidify liquid can be obtained.
According to the present invention, in step (3), the solid phase powder and solidify liquid by mass volume ratio (solid-to-liquid ratio) be 1:1~
3:1 (g/ml) reconciles, it is preferable that is 1.5:1~2:1 (g/ml).
Biologically active Injectable compound bone cement prepared by the present invention has good syringeability, anti-collapsibility
And mechanical property.Meanwhile having excellent bioactivity, biocompatibility and biological degradability, and calcium phosphate (CPC) is not present
The problem of collapsing with calcium sulfate (CSC) the bone cement later period can provide effective support in a long time, can be used for sclerotin and dredge
The treatment of loose vertebral compression fracture or collapse of vertebra (is used to prepare treatment Treatment of osteoporotic vertebral compression fractures or collapse of vertebra
Bio-medical material), it can also be used to prepare filling material of bone, Bone Defect Repari bio-medical material or osteanagenesis bio-medical material
Material.
Compared with other prior arts, the invention has the characteristics that:
1. the solidify liquid in composite bone cement of the invention contains chitosan and sodium β-glycerophosphate.Chitosan is a kind of day
Right high molecular material has good adhesiveness, degradability and biocompatibility, has adherency well to make osteoblast
With being introduced into solidify liquid of the invention can be used as strong Binder Phase so as to improve the curing performance of material and greatly mention
The anti-collapsibility of high material.Sodium β-glycerophosphate is a kind of common human body phosphorus replenishers, in addition to this, weakly alkaline β-is sweet
Oleophosphoric acid sodium introduces solidify liquid, and solidify liquid can be made to tend to be neutral；Meanwhile the glycerol group of sodium β-glycerophosphate can be with hydrone
Between by hydrogen bond formed combine water be centered around around chitosan molecule chain, prevent chitosan to be precipitated from solution；Moreover, β-is sweet
Oleophosphoric acid sodium can adjust the sol-gel transition of solidify liquid, to influence the performances such as the solidification rate of system.
2. a small amount of silicate bioactivity glass can only be introduced calcium sulfate bone cement system, and this hair by existing method
The bone cement of bright method preparation can introduce the phosphosilicate bioactivity glass of high-content, can more efficiently play this
Two respective functions of component in invention bone cement solid phase powder.Wherein, the bioactivity glass has good biology
Compatibility and bioactivity can be firmly combined together with the skeletal tissue of surrounding；In fluid environment, quick release
Si, P, Ca plasma out promotes the cell interior of osteoblast metabolism to respond, while improving the degradation property of material；It plants
After entering in vivo, formation on the surface of the material and HA as bone tissue constituent class can be induced, thus between bone tissue and material
Firm chemical bonding is formed, the formation of new bone tissue is induced, so that the composite bone cement be made to have excellent bioactivity.
The calcium sulfate has been widely used in Bone Defect Repari, field of medicaments, can regulate and control the mechanical property and degradation of composite bone cement
Rate.And the raising of the content based on the bioactivity glass, and the chitosan added in above-mentioned solidify liquid is combined, in this hair
While the anti-collapsibility of bright bone cement significantly improves, degradation rate is significantly improved with human body bone uptake rate-matched.
3. composite bone cement of the invention has excellent bioactivity, biocompatibility and biological degradability.It is simulating
In body fluid (SBF) culture, composite bone cement surface forms HA；After cultivating 12 weeks, in the case where the degradation of calcium sulfate almost all,
The original shape of composite bone cement still without significant change, there is certain mechanical support intensity, and there is no after CPC and CSC bone cement
The problem of phase collapses can grow for bone and its cells and provide necessary " bridge ", there is good potential applicability in clinical practice.
4. composite bone cement of the invention has excellent syringeability and anti-collapsibility, can be incited somebody to action using ordinary syringe
It is injected into Bone Defect Repari position, can be used for minimal invasive operation.
Detailed description of the invention
Fig. 1 is that composite bone cement solidifies appearance picture after demoulding in embodiment 1.
Fig. 2 be embodiment 1 in different solid than when composite bone cement injection rate.
Fig. 3 is the compressive strength of composite bone cement in embodiment 2-4.
Fig. 4 be in embodiment 3 composite bone cement in vitro in activity experiment different time surface topography scanning electron microscope (SEM) photograph.
The a figure time is 0 day, and the b figure time is 1 week, and the c figure time is 3 weeks, and the d figure time is 8 weeks.
Fig. 5 is X-ray diffractogram of the composite bone cement after simulated body fluid culture 8 weeks in embodiment 6.
Fig. 6 is the degradation in vitro of composite bone cement and existing calcium sulfate bone cement in different time points in embodiment 3
(weight loss) compares.
Fig. 7 is the degradation in vitro of composite bone cement and existing calcium sulfate bone cement in different time points in embodiment 3
(diameter change) compares, and a figure is calcium sulfate bone cement, and b figure is composite bone cement, and c figure is calcium sulfate bone cement and Composite Bone water
Mud diameter change statistical result comparison diagram.
Fig. 8 is the cell proliferation experiment of composite bone cement and existing calcium sulfate bone cement in embodiment 2 and embodiment 3:
Cell is MG-63 cell, and culture is detected after 1 day with mtt assay.
Fig. 9 is the cell adhesion experiments of composite bone cement in embodiment 3: cell is MG-63 cell.
Specific embodiment
As described above, traditional preparation method is done with water or physiological saline and is solidified usually using half-H 2 O calcium sulphate as cured matrix
Phosphosilicate bioactivity glass (SPBG) is introduced system by agent in the form of filler.The study found that since SPBG itself does not have
There is the characteristic of spontaneous coagulation, therefore above-mentioned system is only capable of introducing a small amount of SPBG, otherwise, a large amount of SPBG can seriously destroy half water sulphur
Sour calcium is formed by structure when solidifying, and causes that system cannot solidify or cured strength cannot be met the requirements.In addition, traditional system
Why there is a problem of that degradation is too fast, mainly calcium sulfate itself is degraded quickly, and SPBG content is less in system, in sulfuric acid
SPBG cannot interconnect to form block-like network after calcium has been degraded, can only in the form of granules " defeated and dispersed ".
Based on this, the present invention provides a kind of novel Injectable compound bone cement and preparation method thereof, by solidify liquid
The middle method for introducing chitosan, sodium β-glycerophosphate (preferably five water sodium β-glycerophosphates), can greatly improve SPBG/ calcium sulfate
The content of SPBG in composite bone cement, makes the composite bone cement while having good biological activity and mechanical property, also has
It is the shortcomings that having excellent anti-collapsibility and biological degradability, effectively overcoming conventional method, with important application prospects.It is non-
Limitation, possible mechanism is: if SPBG content height is to a certain extent, the HA that the surface SPBG is formed in body fluid can be
They are connected with each other, and form blocky network, thus remain to provide certain support after calcium sulfate is degradable, thus
It is too fast to solve system degradation in the prior art, the problem of " bridge " is provided cannot be grown for cell.
Further, solidify the sol-gel transition for relying primarily on solidify liquid and solidify liquid system early period of the present invention and consolidate
Interaction between phase powder, later period maintain shape mainly by formation connected network between the HA of SPBG and SPBG Surface Creation
Shape provides mechanics support and cell growth " bridge ", is applicable not only to addition half-H 2 O calcium sulphate, can also use dead plaster
And calcium sulphate dihydrate.And traditional system solidifies and relies primarily on half-H 2 O calcium sulphate aquation into the crystal transfer of calcium sulphate dihydrate, it can only
Use half-H 2 O calcium sulphate.
The present invention is further explained with example with reference to the accompanying drawing.But those skilled in the art understands, guarantor of the invention
Shield range is not limited only to following embodiment.According to the present disclosure, those skilled in the art will appreciate that not departing from
In the case where technical characteristic and range that technical solution of the present invention is given, many change and modification are made to following embodiment and are all belonged to
In protection scope of the present invention.Raw material used in following embodiments is unless otherwise specified that can be commercially available
's.
Embodiment 1
(1) according to the composition and ratio of bioactivity glass, respectively with ethyl orthosilicate, triethyl phosphate, four water-calcium nitrate,
Sodium nitrate is the presoma of silicon, phosphorus, calcium, sodium, and nitric acid is catalyst, is prepared into 46.1%SiO using sol-gel method2-
26.9%CaO-2.6%P2O5- 24.4%Na2O (mol.%) bulk material.It is crushed, to obtain powder by screening spare.It will be above-mentioned
Powder is spiked into half-H 2 O calcium sulphate according to the 50% of solid phase powder total amount, is uniformly mixed, is obtained solid phase powder.
(2) preparation of solidify liquid
Preparation contains 2.5% chitosan, and 2.5g chitosan the solidify liquid of 8% 5 water sodium β-glycerophosphate: is dissolved in 74.5g second
It in acid solution (1mol/L), stirs to clarify transparent, obtains chitosan aqueous solution.Five water sodium β-glycerophosphate of 8g is weighed to be dissolved in
It in 15g acetic acid solution (1mol/L), then is instilled in above-mentioned chitosan aqueous solution dropwise under the action of stirring, as Composite Bone water
The solidify liquid of mud.
(3) preparation of composite bone cement
It is respectively 1:1 according to solid-to-liquid ratio by the middle solidify liquid prepared of the solid phase powder and step (2) that are prepared in step (1),
1min is sufficiently stirred in 2:1,3:1 (g/ml), reconciles into paste, injects mold cured.Curing time difference is measured with Vicat apparatus
It for 80min, 36min, 24min, demoulds and takes out after room temperature curing, obtain the smooth cylindrical body (Fig. 1) in surface, i.e., it is of the invention
Composite bone cement.
Utilize the syringeability energy of injector for medical purpose characterization Injectable compound bone cement.Syringe before precise is tested
Weight M0, by mass M after the paste loading syringe of reconciliation1, and will be after composite bone cement slurry extrusion injector for medical purpose
Weight M2, the injection rate (Fig. 2) of composite bone cement is calculated using formula (1).
Formula (1): injection rate J%=[(M1-M2)÷(M1-M0)] * 100%
As shown in Figure 2, with the increase of bone cement solid-to-liquid ratio, the syringeability of bone cement can decline.Adjustable solid-liquid
Than enabling composite bone cement to have good syringeability, being used for minimal invasive operation bone injury.
Embodiment 2
(1) preparation of solid phase powder
According to the composition and ratio of bioactivity glass, respectively using ethyl orthosilicate, phytic acid, four water-calcium nitrate as silicon, phosphorus, calcium
Presoma, 54.2%SiO is prepared into using sol-gel method2- 35%CaO-10.8%P2O5(mol.%) bulk material.Through
Crush, screen powder is spare.Above-mentioned bioactivity glass powder is spiked into half water sulphur according to the 30% of solid phase powder total amount
In sour calcium, it is uniformly mixed, obtains solid phase powder.
(2) preparation contains 1.75% chitosan, and the solidify liquid of 7% 5 water sodium β-glycerophosphate: 1.75g chitosan is dissolved in
It in 77.25g acetic acid solution (1mol/L), stirs to clarify transparent, obtains chitosan aqueous solution.Weigh five water β of 7g-phosphoglycerol
Sodium is dissolved in 14g acetic acid solution (1mol/L), then is instilled in above-mentioned chitosan aqueous solution dropwise under the action of stirring, as multiple
Close the solidify liquid of bone cement.
(3) preparation of composite bone cement
It according to solid-to-liquid ratio is 2:1 (g/ml) by the solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1)
1min is sufficiently stirred, reconciles into paste.By the paste of reconciliation, paste is injected into mold with syringe, room temperature is solid
It demoulds and takes out after change, obtain the smooth cylindrical body in surface.Curing time is 35min.Compressive strength after solidification is 6.04
± 0.43Mpa (Fig. 3), in compressive strength (2~12Mpa) range for the cancellous bone that document is reported；Compression modulus be 362 ±
149MPa also complies with the requirement (100~500MPa) of cancellous bone, shows that this composite bone cement is expected to the substitution as cancellous bone
Or repair materials, treat bone injury.The composite bone cement does not have cytotoxicity (Fig. 8).
Embodiment 3
(1) with embodiment 2,54.2%SiO is prepared2- 35%CaO-10.8%P2O5(mol.%) bioactivity glass powder
Material.It is spiked into half-H 2 O calcium sulphate according to the 55% of solid phase powder total amount, is uniformly mixed, obtains solid phase powder.
(2) with step (2) in embodiment 2
(3) preparation of composite bone cement
It according to solid-to-liquid ratio is 2:1 (g/ml) by the solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1)
1min is sufficiently stirred, reconciles into paste.Mechanical strength decreases compared with Example 2 after solidification, but still meets cancellous bone
Requirement (Fig. 3).After cultivating 1 week in SBF, compressive strength reaches 15.5 ± 2.8Mpa, detects great amount of hydroxy group apatite
(HA) (Fig. 4) is deposited.Before culture, the intensity after culture improves a lot, this may be the HA and bioactivity of deposition
Structure interconnected is formed between glass or HA and HA.Meanwhile a large amount of depositions of HA, it is external to show that the bone cement has
Bioactivity.It impregnates in SBF 8 weeks, surface forms fine and close HA (Fig. 4), and without phenomenon of collapsing, compressive strength is 3.4 ± 1.2Mpa,
Effective mechanical support can be provided, and provided " bridge " for bone and its cells growth, Bone Defect Repari is promoted.
After SBF impregnates 12 weeks, composite bone cement quality about 50% (Fig. 6) of degradation, while diameter is without significant change (figure
7) the existing layer-by-layer spallation problems of calcium sulfate bone cement, are not present, are expected to provide long term support when treating bone injury, solve existing
The problem of providing support cannot be grown for cell by having the bone cement later period to collapse.The composite bone cement does not have cytotoxicity (Fig. 8),
Cell can be very good the surface (Fig. 9) for being adhered to it.
Embodiment 4
(1) with embodiment 2,54.2%SiO is prepared2- 35%CaO-10.8%P2O5Bioactivity glass powder.It is pressed
It is spiked into half-H 2 O calcium sulphate according to the 75% of solid phase powder total amount, 99%, is uniformly mixed, obtains solid phase powder.
(2) with step (2) in embodiment 2
(3) preparation of composite bone cement
It with the solidify liquid that is prepared in step (2) according to solid-to-liquid ratio is respectively 2:1 by the solid phase powder prepared in step (1)
(g/ml) 1min is sufficiently stirred, reconciles into paste, injects mold cured.The compressive strength of composite bone cement is respectively after solidification
2.74 ± 0.45Mpa, 2.48 ± 0.80Mpa (Fig. 3), compressive strength data in integrated embodiment 2, embodiment 3, after showing solidification
Mechanical strength is declined with the increase of bio-vitric content in solid phase powder.There is HA generation after impregnating SBF, shows
External activity out.
Embodiment 5
(1) 58%SiO is divided into using sol-gel method preparation group2- 38%CaO-4%P2O5Bioactivity glass block-shaped material
Material is crushed, to obtain powder by screening spare.Above-mentioned powder is spiked into dead plaster according to the 75% of solid phase powder total amount
In, it is uniformly mixed, obtains solid phase powder.
(2) preparation of solidify liquid
Preparation contains 5% chitosan, and 5g chitosan the solidify liquid of 9% 5 water sodium β-glycerophosphate: is dissolved in 68g hydrochloric acid solution
It in (1mol/L), stirs evenly, obtains chitosan aqueous solution.It weighs five water sodium β-glycerophosphate of 9g and is dissolved in 18g hydrochloric acid solution
It in (1mol/L), then is instilled in above-mentioned chitosan aqueous solution dropwise under the action of stirring, as the solidify liquid of composite bone cement.
(3) preparation of composite bone cement
It according to solid-to-liquid ratio is 2.5:1 (g/ by the solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1)
Ml 1min) is sufficiently stirred, reconciles into paste, the smooth cylindrical body composite bone cement in surface is obtained after solidification.
Utilize the anti-collapsibility of phosphate buffer (PBS) test composite bone cement.The paste for having been reconciled 2g with syringe
Shape object injects in phosphate buffer (PBS), is placed in 37 DEG C of environment.It is observed after 24 hours, composite bone cement is without obvious defeated and dispersed
Phenomenon takes out not defeated and dispersed part, freeze-drying, weighing (W2), the paste for separately taking 2g to reconcile is freeze-dried, weigh (W1),
It is 93% using the anti-collapsibility D that formula (2) calculate composite bone cement.Compared to existing calcium sulfate bone cement (α-half water sulphur
Sour calcium and physiological saline reconcile by solid-to-liquid ratio 2:1g/ml) larger area it is defeated and dispersed, and there is little particle to fall within container bottom phenomenon and
Speech, the composite bone cement anti-collapsibility are good.
Formula (2): anti-collapsibility D%=W2/W1* 100%
Wherein, W1For the dry weight of 2g bone cement (not impregnating PBS), W2For the dry weight of bone cement after immersion PBS.
Embodiment 6
(1) 70%SiO is divided into using sol-gel method preparation group2- 30%CaO bioactivity glass bulk material, ball milling
It crushes, to obtain powder by screening spare.Above-mentioned powder is spiked into dead plaster according to the 60% of solid phase powder total amount, is mixed
Uniformly, solid phase powder is obtained.
(2) preparation of solidify liquid
Preparation contains 1% chitosan, and 1g chitosan the solidify liquid of 4% 5 water sodium β-glycerophosphate: is dissolved in 85g acetic acid solution
It in (0.1mol/L), stirs to clarify transparent, obtains chitosan aqueous solution.It weighs five water sodium β-glycerophosphate of 4g and is dissolved in 10g second
It in acid solution (0.1mol/L), then is instilled in above-mentioned chitosan aqueous solution dropwise under the action of stirring, as composite bone cement
Solidify liquid.
(3) preparation of composite bone cement
It according to solid-to-liquid ratio is 2:1 (g/ml) by the solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1)
1min is sufficiently stirred, reconciles into paste, is injected into mold, demoulds and takes out after room temperature curing, it is smooth to obtain surface
Cylindrical body.In the external SBF experiment of the composite bone cement, surface forms close HA accumulation, shows external activity (Fig. 5).
Embodiment 7
(1) 80%SiO is divided into using sol-gel method preparation group2- 16%CaO-4%P2O5Bioactivity glass block-shaped material
Material, ball mill grinding, to obtain powder by screening spare.Above-mentioned powder is spiked into calcium sulphate dihydrate according to the 50% of solid phase powder total amount
In, it is uniformly mixed, obtains solid phase powder.
(2) preparation of solidify liquid
Preparation contains 3% chitosan, and 3g chitosan the solidify liquid of 8% 5 water sodium β-glycerophosphate: is dissolved in 74g acetic acid solution
It in (0.6mol/L), stirs to clarify transparent, obtains chitosan aqueous solution.It weighs five water sodium β-glycerophosphate of 8g and is dissolved in 15g second
It in acid solution (0.6mol/L), then is instilled in above-mentioned chitosan aqueous solution dropwise under the action of stirring, as composite bone cement
Solidify liquid
(3) preparation of composite bone cement
It according to solid-to-liquid ratio is 1.75:1 (g/ by the solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1)
Ml 1min) is sufficiently stirred, reconciles into paste, is injected into mold, demoulds and takes out after room temperature curing, it is smooth to obtain surface
Cylindrical body.The composite bone cement is in SBF after impregnating 8 weeks, and diameter is without significant change, and there is no peeling or collapse phenomena, uses
When making filling material of bone, it is expected to provide long term support for cell growth.
Claims (14)
1. a kind of biologically active Injectable compound bone cement, which is characterized in that the bone cement is by solid phase powder and admittedly
Change liquid two parts composition；Wherein, the solid phase powder is made of phosphosilicate bioactivity glass and calcium sulfate mixing, solidify liquid
In contain chitosan and sodium β-glycerophosphate；
The solid phase powder and the mass volume ratio (solid-to-liquid ratio) of solidify liquid are 1:1~3:1 (g/ml)；
The solid phase powder is grouped as by the group of following weight percent content:
Phosphosilicate bioactivity glass: greater than be equal to 20wt.% but be not 100wt.%；
Calcium sulfate: less than be equal to 80wt.% but be not 0wt.%；
The mass percentage of chitosan is 1wt.%~5wt.% in the solidify liquid, and the quality percentage of sodium β-glycerophosphate contains
Amount is 4wt.%~9wt.%.
2. Injectable compound bone cement according to claim 1, wherein the quality volume of the solid phase powder and solidify liquid
It is 1.5:1~2:1 (g/ml) than (solid-to-liquid ratio).
3. Injectable compound bone cement according to claim 1, wherein the sodium β-glycerophosphate is five water β-glycerol phosphorus
Sour sodium.
4. Injectable compound bone cement according to claim 1, which is characterized in that the solid phase powder is by following weight hundred
The group than content is divided to be grouped as:
Phosphosilicate bioactivity glass: 25wt.%~99wt.%；
Calcium sulfate: 1wt.%~75wt.%.
5. Injectable compound bone cement according to claim 4, which is characterized in that the solid phase powder is by following weight hundred
The group than content is divided to be grouped as:
Phosphosilicate bioactivity glass: 30wt.%~90wt.%；
Calcium sulfate: 10wt.%~70wt.%.
6. Injectable compound bone cement according to claim 1, wherein the phosphosilicate bioactivity glass composition
Are as follows: x (SiO2)·y(CaO)·m(P2O5)·n(Na2O), wherein x, y, m, n range (mol.%) are as follows: x 45mol.%
~80mol.%, y are 15mol.%~40mol.%, and m is 0mol.%~11mol.%, and n is 0mol.%~25mol.%.
7. Injectable compound bone cement according to claim 1, wherein the calcium sulfate is α-half-H 2 O calcium sulphate, β-half
One of H 2 O calcium sulphate, calcium sulphate dihydrate, dead plaster are a variety of.
8. Injectable compound bone cement according to claim 1, which is characterized in that also containing containing sour water in the solidify liquid
Solution.
9. Injectable compound bone cement according to claim 8, wherein the solidify liquid by following mass percent group
It is grouped as:
Chitosan 1wt.%~5wt.%
Sodium β-glycerophosphate 4wt.%~9wt.%
86wt.% containing aqueous acid~95wt.%.
10. Injectable compound bone cement according to claim 8 or claim 9, wherein described containing aqueous acid be concentration is 0.1
One of the acetic acid aqueous solution of~1mol/L, aqueous hydrochloric acid solution, aqueous citric acid solution.
11. the preparation method of any one of the claim 1-10 Injectable compound bone cement, which is characterized in that the method packet
Containing following steps:
(1) preparation of solid phase powder
Powder is made in phosphosilicate bioactive glass material；Calcium sulfate is spiked into the bioactivity glass powder,
It is uniformly mixed, obtains solid phase powder；
(2) preparation of solidify liquid
Chitosan and sodium β-glycerophosphate in solidify liquid and the other components in solidify liquid are mixed to get the solidify liquid；
(3) preparation of composite bone cement
The solidify liquid prepared in the solid phase powder and step (2) that prepare in step (1) is reconciled, the composite bone cement is obtained.
12. preparation method according to claim 11, which is characterized in that step (2) specifically: the solidify liquid is by following
The group of mass percent is grouped as: chitosan 1wt.%~5wt.%, sodium β-glycerophosphate 4wt.%~9wt.%, and contains sour water
Solution 86wt.%~95wt.%；It is matched according to above-mentioned solidify liquid, the chitosan of solidify liquid total amount 1wt.%~5wt.% will be accounted for
It is added containing in aqueous acid, is stirred to clear, obtains chitosan aqueous solution；Then, solidify liquid total amount will be accounted for
The sodium β-glycerophosphate of 4wt.%~9wt.% is dissolved in containing in aqueous acid, then to instill under the action of stirring the shell dropwise poly-
In sugar aqueous solution, the solidify liquid is obtained.
13. the purposes of any one of the claim 1-10 Injectable compound bone cement, which is characterized in that be used to prepare treatment bone
The bio-medical material of the loose vertebral compression fracture of matter or collapse of vertebra.
14. the purposes of any one of the claim 1-10 Injectable compound bone cement, which is characterized in that be used to prepare bone filling
Material, Bone Defect Repari bio-medical material or osteanagenesis bio-medical material.
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| CN108114312A (en) * | 2018-02-26 | 2018-06-05 | 王由 | A kind of plasticity 45S5 bioactivity glass and preparation method thereof |
| CN108273131B (en) * | 2018-03-19 | 2021-07-27 | 深圳市中科海世御生物科技有限公司 | Composite bone cement, preparation method and application thereof, and bone repair material |
| CN108714244B (en) * | 2018-06-05 | 2021-05-04 | 黄冈师范学院 | Mesoporous bioglass/graphene oxide composite bone cement and preparation method thereof |
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| CN110498664B (en) * | 2019-09-17 | 2021-11-30 | 扬州大学 | Preparation method of high-strength injectable multiphase calcium phosphate-based bone cement |
| CN110755682A (en) * | 2019-10-31 | 2020-02-07 | 湖北联结生物材料有限公司 | Calcium sulfate bone cement containing bioglass and preparation method thereof |
| CN111012946B (en) * | 2019-12-31 | 2022-05-17 | 广州润虹医药科技股份有限公司 | Thermo-sensitive calcium phosphate bone cement and preparation method thereof |
| CN115554468B (en) * | 2022-09-20 | 2023-12-01 | 中科硅骨(东莞)医疗器械有限公司 | Bone cement containing bioactive glass and preparation method and application thereof |
| CN115400272B (en) * | 2022-09-21 | 2023-07-11 | 松山湖材料实验室 | Calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and preparation method thereof |
| CN115770320A (en) * | 2022-12-12 | 2023-03-10 | 浙江工业大学 | Preparation method of magnesium phosphate/phytic acid/gelatin/calcined dolomite bone adhesive |
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