CN112773933A - Bone repair material, preparation method thereof and craniomaxillofacial repair prosthesis - Google Patents
Bone repair material, preparation method thereof and craniomaxillofacial repair prosthesis Download PDFInfo
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- 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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- A61L2430/34—Materials or treatment for tissue regeneration for soft tissue reconstruction
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Abstract
The invention belongs to the technical field of bone repair, and particularly relates to a bone repair material, a preparation method thereof and a craniomaxillofacial repair prosthesis, wherein the bone repair material comprises a main body part and a hydrophilic sponge part, the main body part is subjected to hydrophilic modification and then is connected with the hydrophilic sponge part through hydrogen bonds, the main body part is provided with a through hole structure, and the hydrophilic sponge part is filled in the through hole of the main body part and covers the surface of the main body part; the bone repairing material can increase the interaction of tissue fluid at two sides of the material, provide attachment points for soft tissues, accelerate the fusion of the repairing material and the soft tissues, achieve remarkable repairing effect, and is very suitable for repairing craniomaxillofacial bone defects, especially for repairing craniomaxillofacial bone defects with more soft tissue parts.
Description
Technical Field
The invention belongs to the technical field of bone repair. More particularly, it relates to a bone repairing material and its preparation method and craniomaxillofacial prosthesis.
Background
The craniomaxillofacial bone is one of the most important parts in human skeleton, and if the skull is accidentally injured, the craniomaxillofacial bone not only affects the appearance of a patient and brings an unsafe feeling to the patient, but also can cause brain tissue to be injured again in a more serious way. In order to prevent brain tissue from being damaged again, restore the cranial cavity tightness and not influence the appearance of a patient, the cranio-maxillofacial bone defect is usually repaired by adopting a surgical operation mode.
At present, for repairing bone defects, selected repairing materials mainly comprise autogenous bone, allogenic bone, medical high polymer materials, titanium metal materials, bone cement and the like. For example, the chinese patent application CN108175539A discloses a bone plate for repairing skull defects of a human body, which has a physiological curvature of a plate surface, and is provided with a plurality of through holes, and the edge of the bone plate is connected with a plurality of linking plates through screws; the bone plate is made of medical polyether-ether-ketone polymer materials through individual design and machining. The intracranial discomfort phenomenon caused by the sensitivity to temperature change of a patient after the patient is repaired by the titanium alloy mesh plate is improved, and the artifact problem of the repair of the titanium alloy mesh plate under the influence is eliminated. However, in practical application, the polyether-ether-ketone and other high polymer materials have certain hydrophobicity, and although the through holes are formed, the through holes are small, and the tissue fluid interaction at two sides of the bone plate is difficult, so that the nutrient supply is unbalanced; and the soft tissue has no attachment point, can not be attached to high polymer materials such as polyether-ether-ketone and the like, and is easy to cause the atrophy and exposure of the soft tissue.
Therefore, it is urgently needed to provide a bone repair material which can increase the tissue-fluid interaction, accelerate the rapid fusion of the repair material and the soft tissue and has the function of repairing the soft tissue.
Disclosure of Invention
The invention aims to solve the technical problems of difficult tissue-fluid interaction, unbalanced nutrition supply and easy atrophy and exposure of soft tissues without attachment points of the existing bone repair materials after bone repair surgery, and provides a bone repair material which increases tissue-fluid interaction, accelerates the rapid fusion of the repair material and the soft tissues and has a soft tissue repair function.
The invention also aims to provide a preparation method of the bone repair material with the soft tissue repair function.
Another object of the present invention is to provide a density-differentiated craniomaxillofacial prosthesis.
The above purpose of the invention is realized by the following technical scheme:
a bone repair material comprises a main body part and a hydrophilic sponge part, wherein the main body part is connected with the hydrophilic sponge part through hydrogen bonds after hydrophilic modification, the main body part is provided with a through hole structure, and the hydrophilic sponge part is filled in the through hole of the main body part and covers the surface of the main body part;
wherein the main body part is polyaryletherketone material; the hydrophilic sponge part is made of hydrophilic materials.
The bone repair material mainly comprises a main body part and a hydrophilic sponge part, wherein polyaryletherketone materials of the main body part can be connected with the hydrophilic sponge part through hydrogen bonds after hydrophilic modification treatment, so that the hydrophilic sponge part covering the surface of the main body part has a root-like fixing effect, the displacement and migration of the hydrophilic material on the surface of the main body part are avoided, meanwhile, the main body part comprises a through hole structure, the hydrophilic sponge part penetrates through the through hole structure and covers the surface of the main body part, namely the hydrophilic sponge part and the main body part are mutually nested, the stability of the whole structure is facilitated, the exertion of the flow guide effect of the hydrophilic sponge part is facilitated, and the attachment of soft tissues on the surface of the main body part is promoted. On one hand, the integral hydrophilicity of the material can provide attachment points for soft tissues on the bone repair material, and the fusion of the bone repair material and the soft tissues is accelerated; on the other hand, the main body part particularly has a through hole structure with hydrophilic characteristics, rich tissue fluid on the inner side of the implanted bone repair material can rapidly pass along the capillary structure of the hydrophilic sponge part, so that the interaction of the tissue fluid is remarkably increased, the nutrition effect on soft tissue attached to the outer side of the bone repair material is enhanced, and the atrophy of the soft tissue of the defect part is prevented. The integral structure of the bone repair material can provide certain mechanical support, can increase the interaction of tissue fluid on two sides of the material, provides attachment points for soft tissues, accelerates the fusion of the repair material and the soft tissues, and has obvious soft tissue repair effect.
Preferably, the hydrophilic material is hyaluronic acid and/or gelatin.
Further, the hydrophilic sponge part is modified with a succinimide end group. The bone repair material can be subjected to activation post-treatment after freeze-drying and forming, so that the material is modified with a succinimide end group, the reaction with primary amino groups in soft tissues is facilitated, and the adhesion between the material and the soft tissues is further enhanced.
Furthermore, the porosity of the main body part is less than or equal to 50%, and the cross-sectional area of a single through hole is less than or equal to 30mm2(ii) a Preferably, the porosity of the main body part is 2.5-50%, and the cross-sectional area of a single through hole is 1mm2～30mm2On one hand, the larger porosity and the cross-sectional area of a single through hole are beneficial to the adhesion growth of soft tissues; on the other hand, the larger porosity and the cross-sectional area of a single through hole, the larger the volume of the hydrophilic sponge part in the main body part, namely, the more the hydrophilic sponge part is embedded into the main body part, the more the hydrophilic sponge part is favorable for strengthening the fixation of the hydrophilic material on the surface of the main body part, and the displacement and the wandering of the hydrophilic material are avoided.
Further, the thickness of the main body part is 1.0 mm-4.0 mm, and the thickness of the hydrophilic sponge part covering the surface of the main body part is 0.05 mm-0.2 mm.
Furthermore, the polyaryletherketone material is selected from one or a combination of more than two of polyetheretherketone, polyetherketoneketone and polyetheretherketoneketone.
Further, the surface contact angle of the main body part after hydrophilic modification is less than or equal to 60 degrees.
In addition, the invention also provides a preparation method of the bone repair material, which comprises the following steps:
s1, forming a main body part with a through hole structure by using polyaryletherketone materials in an additive or subtractive mode;
s2, soaking the main body part obtained in the step S1 in concentrated sulfuric acid to modify the surface of the main body part with sulfonic hydrophilic groups to obtain a hydrophilic modified main body part;
and S3, soaking the hydrophilic modified main body part obtained in the step S2 in an aqueous solution of a hydrophilic material, taking out the main body part after the hydrophilic material completely fills the through hole structure of the main body part and covers the surface of the main body part, and freeze-drying the main body part to obtain the hydrophilic modified main body.
The additive mode can be 3D printing, parameters such as aperture porosity of the through hole can be controlled more finely by adopting a 3D printing forming mode, the material reducing mode can be mechanical processing including turning forming, drilling and the like, the forming process is simple, and the purpose of the invention can be achieved.
Further, step S3 is followed by the following steps:
s4, activating the product lyophilized in the step S3 by 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to obtain the bone repair material modified with the succinimide end group.
Specifically, firstly, soaking the freeze-dried bone repair material with a sponge structure on the surface layer in an EDC solution, preferably placing the EDC solution in an ice-water mixed water bath at 0 ℃, further preferably completely soaking and standing the surface of the bone repair prosthesis, which is in contact with soft tissues, in the EDC solution, and standing for 5-10 min; adding an NHS solution at 0 ℃ into the EDC solution, and continuously standing for 5-10 min again; finally, fishing out the bone prosthesis, placing the bone prosthesis in a purified water solution at 0 ℃ for removing redundant EDC and NHS, and replacing the purified water at 0 ℃ for 3-5 times, wherein the infiltration process is not more than 1min each time; and finally, carrying out secondary freeze-drying treatment on the modified bone repair prosthesis material to obtain the bone repair material modified with the succinimide end group.
Preferably, the mass fraction of the EDC solution and the NHS solution is 10% to 20%, more preferably 15%.
Further, in step S2, the temperature of the main body portion being immersed in the concentrated sulfuric acid is 30 ℃ to 70 ℃, preferably 50 ℃, and the reaction time is not less than 0.5 h.
Further, in step S3, the aqueous solution of the hydrophilic material is an aqueous solution of hyaluronic acid and/or gelatin; the mass fraction of the hyaluronic acid aqueous solution is 0.5-10%, preferably 0.5-5%, and more preferably 2%; the mass fraction of the gelatin water solution is 0.5-10%, preferably 2-10%, and more preferably 5%; in the mixed aqueous solution of hyaluronic acid and gelatin, the mass fraction of hyaluronic acid is preferably 1%, and the mass fraction of gelatin is preferably 2%.
Further, in step S3, the hydrophilic modified main body portion obtained in step S2 is immersed in a solution of a hydrophilic material, and the ultrasonic treatment is performed for at least 0.5h, so that the ultrasonic treatment facilitates uniform dispersion of the hydrophilic material, sufficient contact with the main body portion, acceleration and increase of generation of hydrogen bonds between the hydrophilic material and the polyaryletherketone material of the main body portion, and facilitates fixing of the hydrophilic sponge portion in the through hole and/or on the surface of the main body portion. And/or after the hydrophilic material completely fills the through hole structure of the main body part and covers the surface of the through hole structure, clamping one end of the obtained material, lifting upwards at the speed of 1-100 mm/min and taking out, and slowly and uniformly lifting to ensure that the hydrophilic material uniformly covers the surface of the main body part and has certain thickness.
The invention also provides a density-differentiated craniomaxillofacial prosthesis, which is made of a bone repair material, wherein the bone repair material comprises a main body part and a hydrophilic sponge part, and the main body part is connected with the hydrophilic sponge part through a hydrogen bond after hydrophilic modification; wherein the main body part is polyaryletherketone material, and the hydrophilic sponge part is hydrophilic material;
the main body part comprises an integrally formed dense region for bearing force and a sparse region for soft tissue attachment, and the dense region surrounds the periphery of the sparse region and is connected with autologous bone tissue;
the hydrophobic area is provided with a through hole structure, and the hydrophilic sponge is partially filled in the through hole of the hydrophobic area and covers the surface of the hydrophobic area.
The density-differentiated craniomaxillofacial prosthesis provided by the invention is provided with the compact region and the sparse region, and the distribution of the compact region and the sparse region can be set individually according to the defect condition of a patient, wherein the compact region mainly bears the function of mechanical load and protects brain tissues from being injured by external force to a certain extent; the sparse matter area corresponds to a part with small stress in human tissues, such as a part where a temporalis muscle is located, and mainly plays a role in repairing soft tissues, and the reasonable personalized arrangement enables the craniomaxillofacial prosthesis to have the function of repairing soft tissues on the basis of ensuring a certain mechanical protection effect, so that the temporalis muscle atrophy is prevented.
Further, the dense region may contain a through-hole structure or not, and for the dense region containing the through-hole structure, the cross-sectional area of a single through-hole is less than 1mm2The porosity of the dense area is less than 2.5 percent, and the integral mechanical property of the material can be ensured under the condition; the cross-sectional area of a single through hole of the hydrophobic region is 1mm2～30mm2The porosity of the sparse zone is 2.5% -50%, and the soft tissue repair function of the sparse zone is better under the condition.
The invention has the following beneficial effects:
the bone repair material comprises a main body part and a hydrophilic sponge part, wherein the main body part is connected with the hydrophilic sponge part through hydrogen bonds after hydrophilic modification, and is provided with a through hole structure, so that the hydrophilic sponge part is filled in the through hole and covers the surface of the main body part; the stable hydrophilic sponge part can increase the interaction of tissue fluid on two sides of the material, provide attachment points for soft tissues, accelerate the rapid fusion of the bone repair material and the soft tissues and achieve the effect of remarkable repair.
According to the invention, the outer surface of the material is further modified with the succinimide end group which can be connected with the primary amino group in the autologous soft tissue, so that the bone repair material has good adhesion with the soft tissue after being implanted, the bone repair material is beneficial to better adhesion of the external soft tissue on the surface of the bone repair material, tissue fluid is continuously nourished, and the rapid growth of the soft tissue is realized.
The invention relates to a density-differentiated craniomaxillofacial prosthesis, which comprises a main body part and a main body part, wherein the main body part comprises a dense area for bearing force and a sparse area for soft tissue attachment, and the dense area surrounds the periphery of the sparse area and is connected with autologous bone tissues; the craniomaxillofacial prosthesis has the function of soft tissue repair and prevents temporalis atrophy on the basis of ensuring a certain mechanical protection effect.
Drawings
Fig. 1 is a graph showing the pathological results of an animal experiment of the bone repair material prepared in example 2 of the present invention.
Fig. 2 is an animal experimental anatomy diagram of a bone repair material prepared in example 3 of the present invention.
FIG. 3 is a schematic structural diagram of a density-differentiated craniomaxillofacial prosthesis prepared according to example 4 of the present invention; wherein, the porosity of the 1-dense region is 0%; 2-dense region, porosity 2%; 3-hydrophobic region, porosity 50%.
Fig. 4 is an animal experimental anatomy of a bone repair prosthesis prepared in comparative example according to the present invention.
Detailed Description
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
Example 1A bone repair Material
The bone repair material consists of a main body part and a hydrophilic sponge part, wherein the main body part is subjected to hydrophilic modification and then is connected with the hydrophilic sponge part through hydrogen bonds, the main body part is provided with a through hole structure, and the hydrophilic sponge part is filled in the through hole of the main body part and covers the surface of the main body part;
the main body part is polyether-ether-ketone, and the surface contact angle after hydrophilic modification is 60 degrees; the hydrophilic sponge part is hyaluronic acid; the porosity of the through hole structure of the main body part is 30%, and the cross-sectional area of a single through hole is 15mm2(ii) a The thickness of main part is 2.0mm, the thickness that the hydrophilic sponge part covers the main part surface is 0.1 mm.
The preparation method comprises the following steps:
s1, forming a main body part with a through hole structure by 3D printing with polyether-ether-ketone, wherein the weight of the material is 100 g;
s2, soaking the main body part obtained in the step S1 in concentrated sulfuric acid (the concentration of the concentrated sulfuric acid is 98 percent), and reacting for 1h at 50 ℃ to modify the surface of the main body part with sulfonic hydrophilic groups to obtain a hydrophilic modified main body part;
s3, soaking the hydrophilic modified main body part obtained in the step S2 in a 2 wt% hyaluronic acid aqueous solution, performing ultrasonic treatment for 1h, taking out after the hydrophilic material completely fills the through hole structure of the main body part and covers the surface of the main body part, and performing freeze-drying to obtain a bone repair material;
s4, placing the bone repairing material obtained in the S3 into 10% EDC solution, placing the EDC solution into ice-water mixed water, keeping the solution at 0 ℃, standing and infiltrating for 5min, adding 10% NHS solution into the EDC solution, and further standing and infiltrating for 5 min;
s5, placing the bone repair material subjected to the operation of S4 in 0 ℃ purified water with the volume much larger than that of the bone repair material for rinsing, and replacing the 0 ℃ purified water for 5 times, wherein the infiltration time is 0.5min each time;
and S6, taking out the bone repair material subjected to the operation S5, and freeze-drying to obtain the surface modified bone repair material.
Filling inert gas into the materials, sealing, and then performing irradiation sterilization; performing tissue adhesion test of pigskin after sterilization, collecting bone repairing material and thoroughly wetted pigskin, and adhering with an adhesion area of 1cm2The result of the test by using the universal mechanical testing machine shows that the stripping force of the bone repairing material and the pigskin tissue is 5.3N.
Example 2A bone repair Material
The bone repair material consists of a main body part and a hydrophilic sponge part, wherein the main body part is subjected to hydrophilic modification and then is connected with the hydrophilic sponge part through hydrogen bonds, the main body part is provided with a through hole structure, and the hydrophilic sponge part is filled in the through hole of the main body part and covers the surface of the main body part;
wherein the main body part is polyether ketone, and the surface contact angle after hydrophilic modification is 30 degrees; the hydrophilic sponge part is gelatin; the porosity of the through hole structure of the main body part is 10%, and the section of a single through holeThe area is 5mm2(ii) a The thickness of main part is 2.0mm, the thickness that hydrophilic sponge part covers the main part surface is 0.2 mm.
The preparation method comprises the following steps:
s1, forming a main body part with a through hole structure by using polyether ketone through 3D printing, wherein the weight of the material is 50 g;
s2, soaking the main body part obtained in the step S1 in concentrated sulfuric acid (the concentration of the concentrated sulfuric acid is 98 percent), and reacting for 1h at 50 ℃ to modify the surface of the main body part with sulfonic hydrophilic groups to obtain a hydrophilic modified main body part;
s3, soaking the hydrophilic modified main body part obtained in the step S2 in 5 wt% gelatin water solution, performing ultrasonic treatment for 2h, after the hydrophilic material completely fills the through hole structure of the main body part and covers the surface of the main body part, clamping one end of the material, lifting upwards at the speed of 30mm/min to enable the hydrophilic sponge material to uniformly cover the surface of the main body part, taking out and freeze-drying;
s4, placing the bone repairing material obtained in the S3 into an EDC solution with the concentration of 15%, placing the EDC solution into ice-water mixed water, keeping the solution at 0 ℃, standing and infiltrating for 10min, then adding an NHS solution with the concentration of 15% and the temperature of 0 ℃ into the EDC solution, and further standing and infiltrating for 10 min;
s5, placing the bone repair material subjected to the operation of S4 in 0 ℃ purified water which is far more than the bone repair material for rinsing, and replacing the 0 ℃ purified water for 3 times, wherein the infiltration time is 1min each time;
and S6, taking out the bone repair material subjected to the operation S5, and freeze-drying to obtain the surface modified bone repair material.
Filling inert gas into the materials, sealing, and then performing irradiation sterilization; performing tissue adhesion test of pigskin after sterilization, and adhering the bone repair material with thoroughly wetted pigskin with an adhesion area of 1cm2The peeling force of the bone repairing material and the soft tissue is 20.7N according to the test result of the universal mechanical testing machine.
And sampling to carry out a rabbit back implantation test, wherein the implantation time is 3 months, no obvious muscle atrophy is seen at the end, and sampling is carried out for tissue dissection observation: pathological results referring to fig. 1, the lower left corner of the figure is the implantation site of the bone repair material, the upper right corner is the muscle tissue attached above the prosthesis, and the light-colored line indicated by the arrow is the regenerated fibrous connective tissue. Animal experiment results show that after the bone repair material is implanted for 3 months, soft tissues are obviously fused with the bone repair material, and a layer of fibrous connective tissue is visible on the interface of a muscle layer and the bone repair material.
EXAMPLE 3A bone repair Material
The bone repair material consists of a main body part and a hydrophilic sponge part, wherein the main body part is subjected to hydrophilic modification and then is connected with the hydrophilic sponge part through hydrogen bonds, the main body part is provided with a through hole structure, and the hydrophilic sponge part is filled in the through hole of the main body part and covers the surface of the main body part;
the main body part is polyether ether ketone, and the surface contact angle after hydrophilic modification is 44 degrees; the hydrophilic sponge part is gelatin and hyaluronic acid; the porosity of the through hole structure of the main body part is 50%, and the cross-sectional area of a single through hole is 1mm2(ii) a The thickness of main part is 1.0mm, the thickness that the hydrophilic sponge part covers the main part surface is 0.05 mm.
The preparation method comprises the following steps:
s1, machining polyether-ether-ketone to form a main body part with a through hole structure, wherein the weight of the material is 10 g;
s2, soaking the main body part obtained in the step S1 in concentrated sulfuric acid (the concentration of the concentrated sulfuric acid is 98 percent), and reacting for 0.5h at 60 ℃ to modify the surface of the main body part with sulfonic hydrophilic groups to obtain a hydrophilic modified main body part;
s3, soaking the hydrophilic modified main body part obtained in the step S2 in a mixed aqueous solution containing 2 wt% of gelatin and 1 wt% of hyaluronic acid, performing ultrasonic treatment for 1h, taking out after the hydrophilic sponge material completely fills the through hole structure of the main body part and covers the surface of the through hole structure, and freeze-drying to obtain the bone repair material.
Filling inert gas into the materials, sealing, and then performing irradiation sterilization; after the sterilization is finished, the tissue adhesion test of the pigskin is carried out, the bone repairing material and the fully wetted pigskin are taken for adhesion,the adhesion area is 1cm2The results of the test using the universal mechanical testing machine showed that the peel force between the prosthetic bone and the pigskin tissue was 3.2N.
Sampling again to carry out a rabbit back implantation test, wherein the implantation time is 3 months, and after the implantation time is up, carrying out tissue dissection and sampling observation; referring to fig. 2, animal experiment results show that the muscle layer is completely wrapped on the surface of the bone repair material after the bone repair material is implanted for 3 months.
Example 4 Density-differentiated craniomaxillofacial prosthesis
The craniomaxillofacial prosthesis is made of a bone repair material, the bone repair material comprises a main body part and a hydrophilic sponge part, and the main body part is connected with the hydrophilic sponge part through hydrogen bonds after hydrophilic modification; the main body part comprises an integrally formed dense region for bearing force and a sparse region for soft tissue attachment, and the dense region surrounds the periphery of the sparse region and is connected with autologous bone tissue;
the dense region comprises a portion having a porosity of 0 and a porosity of 2%, wherein the cross-sectional area of a single through-hole having a portion having a porosity of 2% is 4mm2The thickness of the dense region part is 5.0mm, the porosity of the sparse region is 50%, and the cross-sectional area of a single through hole of the sparse region is 9mm2And the thickness of the lyophobic part is 2.0 mm. The thickness of the hydrophilic sponge part covering the surface of the main body part is 0.2 mm. The structure of the obtained craniomaxillofacial prosthesis is schematically shown in figure 3.
The preparation method comprises the following steps:
s1, designing the porosity of the dense area and the sparse area of the main body part, and forming the main body part by 3D printing with polyether-ether-ketone, wherein the weight of the material is 113 g;
s2, soaking the main body part obtained in the step S1 in concentrated sulfuric acid (the concentration of the concentrated sulfuric acid is 98 percent), and reacting for 1h at 30 ℃ to modify the surface of the main body part with sulfonic hydrophilic groups to obtain a hydrophilic modified main body part;
s3, soaking the hydrophilic modified main body part obtained in the step S2 in an aqueous solution containing 10 wt% of gelatin, performing ultrasonic treatment for 1h, taking out after the hydrophilic sponge material completely fills the through hole structure of the main body part and covers the surface of the main body part, and freeze-drying;
s4, placing the craniomaxillofacial prosthesis obtained in the step S3 in 15% EDC solution, and placing the EDC solution in ice-water mixed water, wherein the temperature of the solution is 0 ℃. Standing and infiltrating the face, close to the temporalis muscle soft tissue side, of the implanted craniomaxillofacial prosthesis into the EDC solution for 5min, then adding an NHS solution with the concentration of 10% and the temperature of 0 ℃ into the EDC solution, and further standing and infiltrating for 10 min;
s5, placing the craniomaxillofacial prosthesis subjected to the operation of S4 in 0 ℃ purified water which is far more than the bone repair material for rinsing, and replacing the 0 ℃ purified water for 3 times, wherein the infiltration time is 0.5min each time;
and S6, taking out the craniomaxillofacial prosthesis subjected to the operation of S5, and freeze-drying to obtain the craniomaxillofacial prosthesis with the surface modified.
Filling inert gas into the craniomaxillofacial prosthesis for sealing, and then irradiating for sterilization; performing pig skin tissue adhesion test after sterilization, and adhering the dense region and sparse region with the thoroughly wetted pig skin tissue with an adhesion area of 1cm2The peel force between the test result and the skin tissue of the pig is 29.8N; the stripping force of the compact area and the pigskin tissue is 10.7N.
Comparative example a bone prosthesis
The bone repair prosthesis comprises a main body part and a sponge part, wherein the main body part is not modified by hydrophilic modification, and the main body material has no through hole structure.
The main body part is polyetheretherketone ketone, and the surface contact angle of the main body part which is not subjected to hydrophilic modification is 120 degrees; the hydrophilic sponge part is gelatin; the thickness of the main body portion is 1.0 mm.
The preparation method comprises the following steps:
s1, cutting polyether-ether-ketone by a numerical control machine tool to form a main body part of a through-hole-free structure, wherein the weight of the material is 20 g;
s2, soaking the main body obtained in the step S1 in an aqueous solution, and reacting for 1h at 60 ℃;
s3, soaking the main body part obtained in the step S2 in a gelatin aqueous solution containing 3 wt%, performing ultrasonic treatment for 1h, taking out, and performing freeze-drying;
s4, placing the bone repair prosthesis obtained in the S3 into 10% EDC solution, placing the EDC solution into ice-water mixed water, keeping the solution at 0 ℃, standing and infiltrating for 10min, then adding 20% NHS solution into the EDC solution, and further keeping standing and infiltrating for 10 min;
s5, placing the bone repair prosthesis which is finished with the operation of S4 in 0 ℃ purified water with the volume far larger than the lifting volume of the bone repair prosthesis for rinsing, and replacing the 0 ℃ purified water for 5 times, wherein the infiltration time is 1min each time;
and S6, taking out the bone repair material subjected to the operation of S5, and freeze-drying to obtain the surface modified bone repair prosthesis.
Filling inert gas into the bone repair prosthesis, sealing, and performing irradiation sterilization; after the sterilization, the adhesion test of the pigskin tissue is carried out, the middle of the bone prosthesis is taken for adhesion, and the adhesion area is 1cm2The test result shows that the stripping force of the bone prosthesis and the soft tissue is 1.0N.
Sampling and carrying out a rabbit back implantation test, wherein the implantation time is 3 months, and after the period, carrying out tissue dissection and sampling observation; referring to fig. 4 in detail, the results of the animal experiments showed that the muscle layer was completely free from adhesion to the bone prosthesis 3 months after the bone prosthesis was implanted.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (12)
1. The bone repair material is characterized by comprising a main body part and a hydrophilic sponge part, wherein the main body part is subjected to hydrophilic modification and then is connected with the hydrophilic sponge part through hydrogen bonds, the main body part is provided with a through hole structure, and the hydrophilic sponge part is filled in the through hole of the main body part and covers the surface of the main body part;
wherein the main body part is polyaryletherketone material; the hydrophilic sponge part is made of hydrophilic materials.
2. The bone repair material according to claim 1, wherein the hydrophilic material is hyaluronic acid and/or gelatin; preferably, the hydrophilic sponge moiety is modified with a succinimide end group.
3. The bone repair material according to claim 1, wherein the porosity of the main body portion is 50% or less, and the sectional area of the single through-hole is 30mm or less2(ii) a Preferably, the porosity is 2.5-50%, and the cross-sectional area of a single through hole is 1mm2～30mm2。
4. The bone repair material as set forth in claim 1, wherein the main body portion has a thickness of 1.0mm to 4.0mm, and the hydrophilic sponge portion has a thickness of 0.05mm to 0.2mm covering the surface of the main body structure.
5. The bone repair material according to claim 1, wherein the body portion has a surface contact angle of 60 ° or less after the hydrophilic modification.
6. A method for preparing a bone repair material according to any one of claims 1 to 5, comprising the steps of:
s1, forming a main body part with a through hole structure by using polyaryletherketone materials in an additive or subtractive mode;
s2, soaking the main body part obtained in the step S1 in concentrated sulfuric acid to modify the surface of the main body part with sulfonic hydrophilic groups to obtain a hydrophilic modified main body part;
and S3, soaking the hydrophilic modified main body part obtained in the step S2 in an aqueous solution of a hydrophilic material, taking out the main body part after the hydrophilic material completely fills the through hole structure of the main body part and covers the surface of the main body part, and freeze-drying the main body part to obtain the hydrophilic modified main body.
7. The method according to claim 6, further comprising the following steps after step S3:
s4, activating the product lyophilized in the step S3 by 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide to obtain the bone repair material modified with succinimide end groups.
8. The method according to claim 6, wherein the main body is soaked in concentrated sulfuric acid at a temperature of 30 ℃ to 70 ℃, preferably 50 ℃ in step S2; the reaction time is not less than 0.5 h.
9. The method of claim 6, wherein in step S3, the hydrophilically modified body portion obtained in step S2 is immersed in a solution of a hydrophilic material: ultrasonic treatment is not less than 0.5 h; and/or after the hydrophilic material completely fills the through hole structure of the main body part and covers the surface of the through hole structure, clamping one end of the material, and pulling upwards at the speed of 1-100 mm/min for taking out.
10. The method for preparing a bone repair material according to claim 6, wherein the hydrophilic material is hyaluronic acid and/or gelatin, and wherein the concentration of the hyaluronic acid aqueous solution is 0.5-5% by mass, and the concentration of the gelatin aqueous solution is 2-10% by mass.
11. The craniomaxillofacial prosthesis with the density difference is characterized in that the craniomaxillofacial prosthesis is made of a bone repair material, the bone repair material comprises a main body part and a hydrophilic sponge part, and the main body part is connected with the hydrophilic sponge part through hydrogen bonds after being subjected to hydrophilic modification; wherein the main body part is polyaryletherketone material, and the hydrophilic sponge part is hydrophilic material;
the main body part comprises an integrally formed dense region for bearing force and a sparse region for soft tissue attachment, and the dense region surrounds the periphery of the sparse region and is connected with autologous bone tissue;
the hydrophobic area is provided with a through hole structure, and the hydrophilic sponge is partially filled in the through hole of the hydrophobic area and covers the surface of the hydrophobic area.
12. Craniomaxillofacial prosthesis according to claim 11, wherein said compact zone is optionally free of a through-hole structure, said compact zone having a single through-hole cross-sectional area < 1mm2The porosity of the dense region is less than 2.5 percent; the cross-sectional area of a single through hole in the hydrophobic area is 1mm2～30mm2The porosity of the lyophobic area is 2.5-50%.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050147656A1 (en) * | 2001-06-14 | 2005-07-07 | Hemcon, Inc. | Tissue dressing assemblies, systems, and methods formed from hydrophilic polymer sponge structures such as chitosan |
| CN104667345A (en) * | 2015-01-30 | 2015-06-03 | 深圳迈普再生医学科技有限公司 | Cranioplasty prosthesis with biological activity and preparation method of cranioplasty prosthesis |
| JP2016209197A (en) * | 2015-05-01 | 2016-12-15 | 国立大学法人信州大学 | Resin implant material and method for producing the same |
| CN108175539A (en) * | 2016-12-08 | 2018-06-19 | 西安康拓医疗技术有限公司 | A kind of human skull's defect repair bone plate and preparation method thereof, application method |
| CN108273137A (en) * | 2018-01-02 | 2018-07-13 | 山东百多安医疗器械有限公司 | A kind of porous bionical material for repairing skull and personalized production method |
| CN108478849A (en) * | 2018-02-07 | 2018-09-04 | 广州迈普再生医学科技股份有限公司 | One kind is absorbable can to stick styptic sponge and preparation method thereof |
| CN109223248A (en) * | 2018-11-29 | 2019-01-18 | 北京奥精医药科技有限公司 | A kind of skull repairing body and preparation method thereof inducing bone tissue regeneration |
| CN109464711A (en) * | 2018-11-07 | 2019-03-15 | 山东省药学科学院 | A kind of amphipathic medical soft tissue repairs microporous barrier and its preparation method and application |
| US20200179569A1 (en) * | 2016-11-25 | 2020-06-11 | Stimos Gmbh | Material for a bone implant and method for producing the same |
-
2020
- 2020-12-30 CN CN202011631275.7A patent/CN112773933B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050147656A1 (en) * | 2001-06-14 | 2005-07-07 | Hemcon, Inc. | Tissue dressing assemblies, systems, and methods formed from hydrophilic polymer sponge structures such as chitosan |
| CN104667345A (en) * | 2015-01-30 | 2015-06-03 | 深圳迈普再生医学科技有限公司 | Cranioplasty prosthesis with biological activity and preparation method of cranioplasty prosthesis |
| JP2016209197A (en) * | 2015-05-01 | 2016-12-15 | 国立大学法人信州大学 | Resin implant material and method for producing the same |
| US20200179569A1 (en) * | 2016-11-25 | 2020-06-11 | Stimos Gmbh | Material for a bone implant and method for producing the same |
| CN108175539A (en) * | 2016-12-08 | 2018-06-19 | 西安康拓医疗技术有限公司 | A kind of human skull's defect repair bone plate and preparation method thereof, application method |
| CN108273137A (en) * | 2018-01-02 | 2018-07-13 | 山东百多安医疗器械有限公司 | A kind of porous bionical material for repairing skull and personalized production method |
| CN108478849A (en) * | 2018-02-07 | 2018-09-04 | 广州迈普再生医学科技股份有限公司 | One kind is absorbable can to stick styptic sponge and preparation method thereof |
| CN109464711A (en) * | 2018-11-07 | 2019-03-15 | 山东省药学科学院 | A kind of amphipathic medical soft tissue repairs microporous barrier and its preparation method and application |
| CN109223248A (en) * | 2018-11-29 | 2019-01-18 | 北京奥精医药科技有限公司 | A kind of skull repairing body and preparation method thereof inducing bone tissue regeneration |
Non-Patent Citations (2)
| Title |
|---|
| 吴九平等: "聚醚醚酮表面多孔羟基化改性对MC3T3-E1细胞黏附、增殖的影响", 《生物骨科材料与临床研究》 * |
| 章俊良等: "《燃料电池-原理•关键材料和技术》", 31 December 2014, 上海交通大学出版社 * |
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