CN101905032A - Method for forming composite rhBMP-2 elasticity modulus graded porous titanium alloy support rod for femoral head and neck - Google Patents

Method for forming composite rhBMP-2 elasticity modulus graded porous titanium alloy support rod for femoral head and neck Download PDF

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Publication number
CN101905032A
CN101905032A CN2010102265259A CN201010226525A CN101905032A CN 101905032 A CN101905032 A CN 101905032A CN 2010102265259 A CN2010102265259 A CN 2010102265259A CN 201010226525 A CN201010226525 A CN 201010226525A CN 101905032 A CN101905032 A CN 101905032A
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titanium alloy
rhbmp
preparation
porous titanium
modelling quantity
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CN101905032B (en
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郭征
郝玉林
李述军
樊向利
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Fourth Military Medical University FMMU
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Fourth Military Medical University FMMU
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Abstract

The invention relates to a method for forming a composite rhBMP-2 elasticity modulus graded porous titanium alloy support rod for the femoral head and the neck. Titanium alloy powder is prepared with an electrode induction melting gas atomization method, and the integrated elasticity modulus graded porous titanium alloy support rod consisting of a head part, a body part and a tail part is prepared according to actually measured biomechanical parameters of the femoral head, the neck and a rotor, wherein the head part and the body part are prepared by sintering the titanium alloy powder and pore-forming agents through the adoption of a cold rolling method, the tail part is prepared by directly sintering the titanium alloy powder, and the porous titanium alloy support rod is immersed in a rhBMP-2/gelatin controlled release microsphere solution. The product prepared by the method can simulate the biomechanical properties of the femoral head and the neck of a human body to the utmost extent, thereby being beneficial to the stress transfer between materials and bone tissue interfaces, avoiding poor bone restoration caused by the stress shielding effect; and simultaneously, sustained-release microspheres on which bone induced growth factors (rhBMP-2) are loaded endue the materials per se with good bone conductivity.

Description

The construction method of the elastic modelling quantity alternation femoral head and neck porous titanium alloy support stick of compound rhBMP-2
Technical field
The present invention relates to a kind of preparation method for the treatment of the support stick of early ischemic necrosis of femoral head, be specifically related to the construction method of the elastic modelling quantity alternation femoral head and neck porous titanium alloy support stick of a kind of compound rhBMP-2.
Background technology
Ischemic necrosis of femoral head is young and middle-aged common orthopaedic disease.Along with disease progression, the patient that 60-80% arranged owing to collapse of the femoral head, be out of shape and cause that traumatic arthritis has to carry out replacement of total hip, cause great loss for thus patient, family and society.Femur head necrosis early treatment is improper or to treat untimely all are the main causes that cause this consequence.At present the method for early stage femur head necrosis of control and prevention collapse of the femoral head has multiplely, comprises that mainly decompression in restricted heavy burden, the marrow, free fibula transplantation and femur head necrosis rebuild the support fixation of rod etc.
The metal porous tantalum of bone trabecula, elastic modelling quantity are 3.00GPa, and porosity is 70-80%, and it is clinical to be applied to orthopaedics with its excellent biological compatibility and enough mechanical strengths, rebuild rod etc. comprising porous tantalum surface artificial articular prosthesis and femur head necrosis.Femur head necrosis is rebuild rod with the porous tantalum preparation, and is little with wound, go out characteristics such as insufficiency of blood, hospital stays be short and be applied to the early stage downright bad treatment of femoral head more and more, effectively alleviates or stoped the further deterioration of femur head necrosis and subsiding of cartilage surface.Yet, this single porous tantalum rod exists certain deficiency: the one, though the porous tantalum rod can play the certain structure supporting role, but at design aspect and reckon without the variation characteristic of the biomechanics of femoral head and neck, and the biomechanical property (especially elastic modelling quantity aspect) of the nearly section of the femur of human body exists notable difference, regional stress can occur and do not match unavoidably like this, produce stress-shielding effect, thereby influence the bone reconstruction around the support stick; The 2nd, the porous tantalum rod is single porous metal material, does not possess the induced osteogenesis activity, repairs the femoral head tissue of pathological changes with it, is difficult to the satisfied repair of performance; The 3rd, porous tantalum rod complicated process of preparation, domestic no this item technology of preparing still, the complete dependence on import of product.Therefore, the support system of seeking a kind of bionical human femur under loading incidence biomechanics characteristic and having good bone repair ability simultaneously just becomes new problem.
Titanium is as the inert metal element, stable chemical performance, and titanium and alloy material preparation technology thereof are simple, are fit to suitability for industrialized production more.Studies confirm that; porous titanium alloy (Ti2448) material has the favorable tissue compatibility, avirulence; good bone conductibility and enough comprcssive strength; especially its elastic modelling quantity can transfer to and be lower than a lot (0.70GPa<3.00GPa) of porous tantalum; porosity can reach 50~70%; the aperture is 100~500 μ m; and has very big modulability; when guaranteeing mechanical strength; can satisfy of the requirement of the nearly section of femur osseous tissue biomechanics to a greater degree to elastic modelling quantity, thus the needs that satisfy the osseous tissue growth, repair.
On the other hand, bone morphogenetic protein (BMPs) is one group of one group of skeletal growth factor that is present in the substrate, especially the BMP-2 effect is the strongest, can induce undifferentiated mescenchymal stem cell and bone precursor to osteoblastic directed differentiation and propagation, promote the osteoblast differentiation maturation, participate in the growth promoter and the process of reconstruction thereof of bone, and then the damaged reparation of accelerated bone.Gelatine microsphere is as the good slow release system, and it has the favorable tissue compatibility and reliable degradation property, can be used as the carrier of a lot of medicines and somatomedin, forms controlled release system, avoids one of medicine, the factor to cross the property effect.Gelatin-compounded rhBMP-2 microsphere in vivo, can discharge rhBMP-2 slowly along with the degraded of gelatine microsphere, thereby reach persistent, stable bone inductive effect.
Summary of the invention
The objective of the invention is to overcome the deficiency of existing treatment early ischemic necrosis of femoral head method, seek a kind of biomechanics characteristic that can bionical as far as possible human femur under loading incidence, the Stress Transfer that helps material-osseous tissue interface, avoid the bone faulty restoration that causes owing to stress-shielding effect, load the sustained-release micro-spheres of bone inductive factor (rhBMP-2) simultaneously, make material itself have good osteoconductive nature, possess the construction method of the elastic modelling quantity alternation femoral head and neck porous titanium alloy support stick of the compound rhBMP-2 of bone-inducting active preferably simultaneously.
For achieving the above object, the technical solution used in the present invention is:
1) preparation of elastic modelling quantity alternation porous titanium alloy support stick
At first by " electrode induction melting gas atomization " preparation titanium alloy powder, the integrated elastic modelling quantity alternation porous titanium alloy support stick that preparation is made up of head, body and afterbody according to the biomechanical parameter between the femoral head of surveying, cervical region, rotor then;
The preparation of described head is to adopt " cold-rolling practice " that titanium alloy powder and pore creating material polymethyl methacrylate are got the powder block by 1: 1 volume ratio mixed-forming, again the powder block is made at 1000~1400 ℃ of sintering, the particle diameter of pore creating material is the 32-60 order, the length of head is 2.50cm, diameter is 1.00cm, and elastic modelling quantity is 3.00Gpa;
The preparation of described body be adopt " cold-rolling practice " with titanium alloy powder and pore creating material polymethyl methacrylate by 1: the volume ratio mixed-forming of 1-4 gets the powder block, again the powder block is made at 1000~1400 ℃ of sintering, the particle diameter of pore creating material is the 60-100 order, the length of body is 6.50-9.00cm, diameter is 1.00cm, and elastic modelling quantity is 0.70-3.00Gpa;
The preparation of described afterbody is that titanium alloy powder is made at 1000~1400 ℃ of sintering, and the length of afterbody is 1.00cm, and diameter is 1.40cm, and elastic modelling quantity is 15.00GPa, and the surface of afterbody is screw-like, and afterbody bottom surface central authorities are interior hexagonal lock hole;
2) preparation of rhBMP-2/ gelatin control-release microsphere
The gelatin dry powder that adds rhBMP-2, the 1g of 8 μ g by every 100ml plasma water at room temperature stirs, and obtains rhBMP-2/ gelatin control-release microsphere behind the vacuum drying, in-80 ℃ of preservations, with standby;
3) rhBMP-2/ gelatin control-release microsphere and porous titanium alloy support stick is compound
Will be through step 2) the rhBMP-2/ gelatin control-release microsphere of preparation redissolves uniformly according to 1g: 100ml and obtain rhBMP-2/ gelatin control-release microsphere solution in plasma water, to after ultrasonic cleaning, be soaked in earlier 24h in the rhBMP-2/ gelatin control-release microsphere solution through the elastic modelling quantity alternation porous titanium alloy support stick of step 1) preparation again, then under-93.3kPa, the negative pressure pump evacuation is placed 30min, can obtain being rich in the hole porous titanium alloy support stick of the elastic modelling quantity alternation of rhBMP-2/ gelatine microsphere.
Advantage of the present invention is: 1. compare with traditional method such as reduce pressure in the traditional marrow, this prosthetic material has been inherited femoral head and has been rebuild rod advantage in the early stage femur head necrosis of treatment: go out insufficiency of blood, simple, few, the good effect of complication of operation; 2. this prosthetic material has the characteristic of high strength, low elastic modulus, in use, can guarantee the demand of skeleton to prosthetic material intensity, and its elastic modelling quantity is more near osseous tissue, can obviously improve the mechanics transmission of material surface-osseous tissue, thereby avoid stress-shielding effect, promote knitting; 3. the characteristics that this prosthetic material is bigger are, have the elastic modelling quantity transmutability, biomechanics characteristic that can bionical as much as possible femoral head and neck, thus avoid partial stress-shielding effect to a greater extent, promote knitting; 4. this prosthetic material combines with biotic factor (rhBMP-2)/gelatine microsphere, make when originally just having had good bone conductibility, also had controlled, persistent, stable osteoinductive energy, really accomplish to promote to greatest extent the bone reparation of early ischemic necrosis of femoral head, prevent the generation of complication such as collapse of the femoral head.
Description of drawings
Fig. 1 is the electromicroscopic photograph of the porous titanium alloy material for preparing of the present invention;
Fig. 2 is the structural representation of the elastic modelling quantity alternation femoral head and neck porous titanium alloy support stick of the compound rhBMP-2 for preparing of the present invention.
The specific embodiment
Below in conjunction with accompanying drawing the present invention is described in further detail.
Preparation method of the present invention is as follows:
1) preparation of elastic modelling quantity alternation porous titanium alloy support stick
At first by " electrode induction melting gas atomization " preparation titanium alloy powder, adopt " cold-rolling practice " that the titanium alloy powder and the molding of pore creating material polymethyl methacrylate hybrid process of preparation are got the powder block then, the powder block is obtained the porous titanium alloy block materials at 1000~1400 ℃ of sintering.In manufacturing process, according to the biomechanical parameter between the femoral head of surveying, cervical region, rotor, by adjusting the volume ratio of titanium alloy powder and pore creating material polymethyl methacrylate, and the granular size of pore creating material, thereby change the porosity and the aperture of material, so that prepare the integrated porous titanium alloy support stick that matches with human femur under loading incidence biomechanics stage by stage, making the aperture that makes final material is 100~500 μ m, porosity can reach 50~70% (see figure 1)s, and the elastic modelling quantity scope is 0.70~15.00Gpa;
Described integrated porous titanium alloy support stick promptly in a jacket (sheath material adopts pure titanium) wait to be prepared into and carry out machine according to accessory size behind the block materials and add last molding according to the distribution situation uniform distribution of elastic modelling quantity.The porous titanium alloy support stick length that finally makes is about 10.00 ± 2.50cm, considers that skeleton varies in size, and body length is alternation unit with 0.50cm, is made up of head, body and afterbody:
Referring to Fig. 2, head 3: long 2.50cm, diameter 1.00cm, elastic modelling quantity are about 3.00GPa, and the volume ratio of titanium alloy powder and pore creating material is 1: 1, and the pore creating material granular size is the 32-60 order;
Body 4: long 6.50cm, diameter 1.00cm is the changeover portion of an elastic modelling quantity alternation, and elastic modelling quantity is 0.70~3.00Gpa, and the volume ratio of titanium alloy powder and pore creating material polymethyl methacrylate is 1: (1~4), pore creating material granular size are 60~100 orders;
Afterbody 5: long 1.00cm, diameter is 1.40cm, elastic modelling quantity is 15.00GPa, the volume ratio of titanium alloy powder and pore creating material is 1: 0, promptly do not add pore creating material, only obtain the porous titanium alloy block materials, realize the preparation of porous material by the gap between the titanium alloy powder at 1000~1400 ℃ of sintering.The surface is screw-like, is used for being locked of barred body and cortical bone position.Afterbody bottom surface central authorities are interior hexagonal lock hole 6, and the length of side is about 0.30cm, is 0.80cm deeply, is used to screw in the draw-in groove of support stick.The screw-like of tail surface and lock hole all after material is made, form by lathe and milling machine machined.
2) preparation of rhBMP-2/ gelatin control-release microsphere
The gelatin dry powder that adds rhBMP-2, the 1g of 8 μ g by every 100ml plasma water at room temperature stirs, and obtains rhBMP-2/ gelatin control-release microsphere behind the vacuum drying, in-80 ℃ of preservations, with standby;
3) rhBMP-2/ gelatin control-release microsphere and porous titanium alloy support stick is compound
Will be through step 2) the rhBMP-2/ gelatin control-release microsphere of preparation according to 1g: 100ml redissolve uniformly in plasma water rhBMP-2/ gelatin control-release microsphere solution, to after ultrasonic cleaning, be soaked in earlier 24h in the rhBMP-2/ gelatin control-release microsphere solution through the elastic modelling quantity alternation porous titanium alloy support stick of step 1) preparation again, then under-93.3kPa, the negative pressure pump evacuation is placed 30min, can obtain being rich in the hole porous titanium alloy support stick of the elastic modelling quantity alternation of rhBMP-2/ gelatine microsphere 2.

Claims (1)

1. the construction method of the elastic modelling quantity alternation femoral head and neck porous titanium alloy support stick of compound rhBMP-2 is characterized in that:
1) preparation of elastic modelling quantity alternation porous titanium alloy support stick
At first by " electrode induction melting gas atomization " preparation titanium alloy powder, the integrated elastic modelling quantity alternation porous titanium alloy support stick that preparation is made up of head, body and afterbody according to the biomechanical parameter between the femoral head of surveying, cervical region, rotor then;
The preparation of described head is to adopt " cold-rolling practice " that titanium alloy powder and pore creating material polymethyl methacrylate are got the powder block by 1: 1 volume ratio mixed-forming, again the powder block is made at 1000~1400 ℃ of sintering, the particle diameter of pore creating material is the 32-60 order, the length of head is 2.50cm, diameter is 1.00cm, and elastic modelling quantity is 3.00Gpa;
The preparation of described body be adopt " cold-rolling practice " with titanium alloy powder and pore creating material polymethyl methacrylate by 1: the volume ratio mixed-forming of 1-4 gets the powder block, again the powder block is made at 1000~1400 ℃ of sintering, the particle diameter of pore creating material is the 60-100 order, the length of body is 6.50-9.00cm, diameter is 1.00cm, and elastic modelling quantity is 0.70-3.00Gpa;
The preparation of described afterbody is that titanium alloy powder is made at 1000~1400 ℃ of sintering, and the length of afterbody is 1.00cm, and diameter is 1.40cm, and elastic modelling quantity is 15.00GPa, and the surface of afterbody is screw-like, and afterbody bottom surface central authorities are interior hexagonal lock hole;
2) preparation of rhBMP-2/ gelatin control-release microsphere
The gelatin dry powder that adds rhBMP-2, the 1g of 8 μ g by every 100ml plasma water at room temperature stirs, and obtains rhBMP-2/ gelatin control-release microsphere behind the vacuum drying, in-80 ℃ of preservations, with standby;
3) rhBMP-2/ gelatin control-release microsphere and porous titanium alloy support stick is compound
Will be through step 2) the rhBMP-2/ gelatin control-release microsphere of preparation according to 1g: 100ml redissolve uniformly in plasma water rhBMP-2/ gelatin control-release microsphere solution, to after ultrasonic cleaning, be soaked in earlier 24h in the rhBMP-2/ gelatin control-release microsphere solution through the elastic modelling quantity alternation porous titanium alloy support stick of step 1) preparation again, then under-93.3kPa, the negative pressure pump evacuation is placed 30min, can obtain being rich in the hole porous titanium alloy support stick of the elastic modelling quantity alternation of rhBMP-2/ gelatine microsphere.
CN 201010226525 2010-07-14 2010-07-14 Method for forming composite rhBMP-2 elasticity modulus graded porous titanium alloy support rod for femoral head and neck Expired - Fee Related CN101905032B (en)

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Cited By (5)

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Publication number Priority date Publication date Assignee Title
CN102178556A (en) * 2011-04-07 2011-09-14 北京畅想天行医疗技术有限公司 Femoral head support frame and manufacturing method thereof
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
CN104645419A (en) * 2014-12-02 2015-05-27 中国人民解放军第四军医大学 Preparation method of porous titanium-alloy femoral head support rod in bionic bone trabecula structure
CN105796214A (en) * 2016-03-08 2016-07-27 吴志宏 Porous metal cervical interbody fusion cage for directionally and slowly releasing rhBMP-2
CN112168431A (en) * 2020-10-23 2021-01-05 中国人民解放军空军军医大学 Functional bionic porous titanium alloy femoral head support rod and preparation method thereof

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CN101418392A (en) * 2008-12-08 2009-04-29 大连交通大学 Bio-medical porous titanium products and preparation method thereof

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102178556A (en) * 2011-04-07 2011-09-14 北京畅想天行医疗技术有限公司 Femoral head support frame and manufacturing method thereof
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
CN102293693B (en) * 2011-06-01 2013-06-26 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
CN104645419A (en) * 2014-12-02 2015-05-27 中国人民解放军第四军医大学 Preparation method of porous titanium-alloy femoral head support rod in bionic bone trabecula structure
CN105796214A (en) * 2016-03-08 2016-07-27 吴志宏 Porous metal cervical interbody fusion cage for directionally and slowly releasing rhBMP-2
CN112168431A (en) * 2020-10-23 2021-01-05 中国人民解放军空军军医大学 Functional bionic porous titanium alloy femoral head support rod and preparation method thereof

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