CN111166539B - Modularized integrated bone regeneration repair capability test chip and preparation method and application thereof - Google Patents

Abstract

The invention discloses a modularized integrated bone regeneration repair capability test chip, and belongs to the technical field of biomedical engineering. The invention combines the 3D printing technology and the computer chip modularization integration theory, provides a modularized assembled and integrated bone regeneration repair capability test chip, integrates test body units corresponding to different test parameters, screens key parameters favorable for bone regeneration repair in a high throughput manner through in-vivo or in-vitro experiments, greatly improves the biological material optimization design screening efficiency, reduces experimental animals, saves experimental expenses and manpower data, simultaneously avoids the influence of uncontrollable differential factors in a plurality of experiments on experimental results, and can be used for precisely screening bone tissue regeneration biological materials in a high throughput manner.

Description

Modularized integrated bone regeneration repair capability test chip and preparation method and application thereof

Technical Field

The invention belongs to the technical field of biomedical engineering, and particularly relates to a bone regeneration repair capability test chip and a preparation method and application thereof.

Technical Field

Bone defects, i.e., the destruction of the structural integrity of bone, are common clinical conditions. Irreversible bone defects caused by bone defects, osteoporosis, bone tumor excision, accident wounds, congenital deformities and the like are one of the major challenges facing the clinic, so that the demand for bone repair materials is high. It is counted that more than 350 ten thousand patients need to be subjected to bone grafting every year in China, and the patients grow rapidly. With the rise of the health level of people, patients are not satisfied with pain relief and basic exercise function restoration through orthopedic implants at present, but are required to restore the original functions to the maximum extent.

The existing artificial bone repair stent is a potential replacement body of autologous bone. Not only is there a great demand in the market, but the induction and repair of living organisms with non-living materials is also one of the hot spots of current scientific research. The bone repair stent can fill the defect after bone loss after implantation to ensure the structural integrity of the bone, and can be used as a carrier of new tissues. Calcium phosphate is similar to inorganic components in human bone tissue in bone repair materials, and is considered as an ideal bone repair material, and calcium phosphate has been shown to have good osteoinductive and osteoconductive properties in previous studies.

Bone tissue repair and reconstruction is a very complex process, and many factors of the scaffold material affect its repair effect. Influencing factors include the physicochemical properties of the material: composition, phase structure; macroscopic porous structure of material (> 100 um): porous shape, porous size, connectivity of pores, porosity; surface micro-nano structure of material (< 100 um): surface micropores and surface whisker structures. Since 1990, some researchers have developed studies of the effects of the above parameters on bone repair. However, due to different material preparation processes, different experimental animal models are selected, and the differences of analysis technologies are analyzed. The transverse and longitudinal comparison between different research results is difficult, so that the bone repair theory of the calcium phosphate material only establishes a rudiment, and the bone repair theory still needs to be continuously perfected by subsequent researchers.

There are two important indexes in the evaluation of bone repair scaffolds, namely, the phenomenon that bone conduction, i.e., new bone tissue grows along the surface of the scaffold, and the phenomenon that bone induction, i.e., scaffold recruitment growth factors and stem cells, induces new bone tissue in the interior of the scaffold. Osteoinductive is an important evaluation criterion for the level of biological activity of scaffolds. In general, the materials are implanted into non-bone sites (subcutaneous, muscle, etc.) and the scaffolds are observed for the formation of new bone to evaluate the osteoinductive properties. However, it is currently unclear whether or not there are both bone conduction and bone induction phenomena during in situ repair. If the relation between the two can be explained clearly, the bone repair process can be well known, and the basic theory of bone repair is further laid.

In the evaluation of the material repairing capability, the animal body repairing effect is the final evaluation standard of the material performance. But the comparison between the different experimental groups is not obvious due to individual differences of animals. In addition, the screening efficiency of single factor at every turn is not high, can cause economy, manpower, the waste of animal resource. Therefore, how to realize large-scale screening of parameters affecting bone repair is still a problem to be solved.

Disclosure of Invention

Aiming at the technical problems, the invention combines the 3D printing technology with the theory of computer chip modularization integration, provides a modularized assembled and integrated bone regeneration repair capability test chip, integrates test body units corresponding to different test parameters, screens key parameters favorable for bone regeneration repair through in-vivo or in-vitro experiments with high flux, greatly improves the optimal design screening efficiency of biological materials, reduces experimental animals, saves experimental expenses and manpower data, can avoid the influence of uncontrollable factors on experimental results in a plurality of experiments, and can be used for screening advanced bone tissue regeneration biological materials with high flux.

The invention comprises the following technical scheme:

the utility model provides a regeneration repair ability test chip of integrated bone regeneration repair ability test chip of modularization, includes base plate and a plurality of test unit body, the base plate is used for integrating and fixing the test unit body, every test unit body corresponds specific test parameter, be provided with the structure of mutually agreeing with between test unit body and the base plate for can assemble and the stability of post-assembling chip between assurance unit body and the base plate.

Alternatively, in the test chip, different test unit bodies are isolated from each other, so that the environments where the single test unit body is located are relatively independent, and the mutual influence is avoided.

In the test chip, the test unit body and the substrate are detachably connected, so that the chip is convenient to assemble, and each test unit body is conveniently detached for testing and characterization respectively after in-vivo or in-vitro experiments are completed. Further, the structure that mutually agrees between the test unit body and the base plate is the buckle structure that can lock, and this structure can guarantee overall structure's stability, and no glue bonds, has avoided introducing other materials to cause the influence to the test result.

Alternatively, in the test chip, the chip is circular as a whole. The circular structure is adopted, so that the test unit bodies on the test unit bodies are distributed circularly, and therefore, when the chip is tested in vivo or in vitro, the relative position and orientation of each test unit body and the surrounding test environment are guaranteed to be similar, and experimental errors are reduced. Further, the diameter of the round chip is 1-20mm.

Alternatively, in the test chip, the substrate is spoke-shaped and includes a circular periphery and a plurality of spokes extending from the center of the circular periphery to the periphery. The number of the spokes can be flexibly designed according to actual needs so as to assemble different numbers of test unit bodies. The spoke-shaped structure contains more gaps, which is beneficial to the material exchange between the test unit body and the surrounding environment.

Alternatively, in the test chip, the spokes are fixedly connected to the circular periphery. The fixed connection is beneficial to improving the overall stability of the chip.

Alternatively, in the test chip, the spoke is provided with a bayonet matched and matched with the test unit body. The spoke can be used as a connecting site of the test unit bodies and plays a role in isolating adjacent test unit bodies, so that the environments of the single test unit bodies are relatively independent, and the mutual influence is avoided. Further, the number of the spokes is 3-8.

Alternatively, in the above test chip, the test unit body includes an outer ring test unit body and an inner ring test unit body, and after the assembly is completed, the outer ring test unit bodies are mutually spliced to form a chip outer ring, the inner ring test unit bodies are mutually spliced to form a chip inner ring, and the chip outer ring and the inner ring are mutually isolated by a gap structure isolation belt. The gap structure isolation belt divides the chip into two main areas of an inner ring and an outer ring, the outer ring can be used for testing the bone conduction effect of different unit bodies, and the inner ring can be used for evaluating the bone induction effect of different unit bodies. The gap structure isolation belt is used for isolating the bone conduction effect of the outer ring, isolating the mutual influence of the inner layer and the outer layer through the middle gap, and preventing the influence of the surrounding bone tissue on the bone induction result caused by the fact that the surrounding bone tissue grows into the inner part along the material in the in-vivo experiment. Therefore, what parameters are respectively beneficial to bone conduction and bone induction can be selected in the same chip. Further, the width of the gap structure isolation belt is 0.5-3mm.

Alternatively, in the above test chip, the specific test parameters corresponding to the test unit include, but are not limited to, parameters of phase composition, pore structure parameters, grain size, surface roughness, wettability, and the like of the material. In the use process, the test unit bodies corresponding to different test parameters can be designed according to actual test requirements. Alternatively, the single factor may be selected from the same test chip, or multiple factors may be selected simultaneously, and preferably the single factor is selected, that is, the test unit has a single key material parameter with different specifications.

Optionally, in the test chip, the material component used for manufacturing the test unit body is one or more of calcium silicate, tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, monocalcium phosphate and other biological ceramic materials

Alternatively, in the above test chip, the values of the test parameters corresponding to the test unit bodies may be completely different, or partially the same or completely the same, and the test unit bodies having the same values of the test parameters may be used as parallel tests.

In the above test chip, the test unit body is prepared by a 3D printing technology, and the values of the material components, pore structure parameters, physicochemical properties and other test parameters are precisely regulated and customized by the 3D printing technology.

Alternatively, in the above test chip, the substrate is made of one or more of calcium phosphate ceramic (CAP CERAMICS), pure titanium, and titanium alloy (Ti 6Al 4V), preferably a material with good biocompatibility, so as to minimize the influence on the test structure.

The invention also provides a preparation method of the modularized integrated bone regeneration repair capability test chip, which is characterized in that the substrate and the test unit body are prepared by adopting a 3D printing technology. The 3D printing is based on a digital model, and specific materials are stacked and solidified layer by layer through software and a numerical control system, so that the technology for manufacturing the solid product becomes possible to realize the manufacturing of the complex structure. The combination of 3D printing technology and artificial bone repair material is an important trend of current development, and promotes the development of bone repair to precise medical treatment and personalized medical treatment. With the improvement of 3D printing technology, it is possible to process complex models and high-precision models.

Alternatively, in the above preparation method, the 3D printing technology used for customizing the test chip is any one or more of 3D printing technologies such as three-dimensional inkjet printing (Three Dimension Printing,3 DP), selective laser sintering (SELECTIVE LASER SINTERING, SLS), stereolithography (Stereo lithographyAppearance, SLA), digital light processing (DIGITAL LIGHT processing, DLP), and the like.

Alternatively, in the above preparation method, the method includes the steps of:

(1) Determining the number of the test unit bodies and the corresponding specific test parameters according to the test requirement, and designing a model of the test unit bodies and the substrate;

(2) Preparing 3D printing raw materials of the substrate, and preparing corresponding 3D printing raw materials according to specific test parameters corresponding to each test unit body;

(3) Preparing a substrate and a test unit body corresponding to specific test parameters by adopting a 3D printing technology;

(4) And assembling the test unit body and the substrate to obtain the test chip.

Alternatively, in the above preparation method step (1), the corresponding unit bodies are divided according to the experimentally required tested parameters and positions, and models of the unit bodies and the substrate are designed in a computer.

Alternatively, in the step (2) of the preparation method, the raw materials corresponding to the different unit bodies, the photosensitive resin and the photoinitiator are uniformly mixed to obtain the printing ink with different material compositions.

Alternatively, in the above-described preparation method step (3), the configured printing ink is molded into the target unit body and substrate using a 3D printing apparatus.

Alternatively, in the above preparation method step (3), the different unit bodies and the substrate are sintered into bioceramics.

The invention also provides application of the modularized integrated bone regeneration repair capability test chip, which is characterized in that the chip is used for high-throughput screening of advanced bone tissue regeneration biological materials. The chip is particularly used for in-vivo or in-vitro biological evaluation, and appropriate material parameters are selected according to evaluation results.

All of the features disclosed in this specification, or all of the steps in a method or process disclosed, may be combined in any combination, except for mutually exclusive features and/or steps.

The invention has the beneficial effects that:

1. The invention assembles and integrates the modules with different characteristics, such as components of module materials, pore structure parameters of the modules, physicochemical properties of the modules and other assembly units on a circular chip, and intensively screens out key material parameters favorable for bone repair and bone induction. The integrated concept of the computer chip module is extended to the biomedical field, the problem that the experimental sample size is large due to the single factor variable in the past is solved, the phenomenon that the test data cannot be compared due to the difference of experimental animals can be avoided, and the influence of uncontrollable variables in the experiment is greatly reduced.

2. The invention utilizes advanced preparation technology to prepare different unit bodies and substrates, can accurately prepare the materialism factors of single variables, and is beneficial to large-scale test and research of chips.

3. The invention can be used for testing the relation between the osteoinduction and the bone conduction, directly measuring whether the osteoinduction phenomenon exists in the in-situ bone repair process, further knowing the bone repair rule and perfecting the design theory of the osteoinduction regeneration material.

4. The invention can accurately customize the materialism factors of a single variable, realizes simultaneous measurement and screening of a plurality of assembly modules of the single variable, is beneficial to the large-scale high-flux test of the bone regeneration capability of a chip, greatly reduces the experiment cost and ensures accurate experiment results.

Drawings

FIG. 1 is a schematic plan view of a modular integrated bone regeneration and repair capability test chip according to the present invention before assembly;

Fig. 2 is a schematic diagram of a three-dimensional structure of the modular integrated bone regeneration and repair capability test chip before the assembly of the chip;

fig. 3 is a schematic plan view of an assembled modular integrated bone regeneration and repair capability test chip according to the present invention;

Fig. 4 is a schematic diagram of a three-dimensional structure of a modular integrated bone regeneration and repair capability test chip after the assembly of the chip;

reference numerals: 1 is a substrate, 2 is an inner ring test unit body, 3 is an outer ring test unit body, 4 is a gap isolation belt, 5 is a buckle structure, 11 is a spoke, and 12 is the circular periphery of the substrate.

Detailed Description

The above-described aspects of the present invention will be described in further detail below by way of specific embodiments of the present invention. It should not be construed that the scope of the above subject matter of the present invention is limited to the following examples. Any modifications, equivalent substitutions or improvements made by those skilled in the art, without departing from the spirit and principles of the present invention, should be included within the scope of the present invention.

Examples

The utility model provides a regeneration repair ability test chip of integrated bone regeneration repair ability test chip of modularization, includes base plate and a plurality of test unit body, the base plate is used for integrating and fixing the test unit body, every test unit body corresponds specific test parameter, be provided with the structure of mutually agreeing with between test unit body and the base plate for can assemble and the stability of post-assembling chip between assurance unit body and the base plate.

Alternatively, in the test chip, different test unit bodies are isolated from each other, so that the environments where the single test unit body is located are relatively independent, and the mutual influence is avoided.

In the test chip, the test unit body and the substrate are detachably connected, so that the chip is convenient to assemble, and each test unit body is conveniently detached for testing and characterization respectively after in-vivo or in-vitro experiments are completed. Further, the structure that mutually agrees between the test unit body and the base plate is the buckle structure that can lock, and this structure can guarantee overall structure's stability, and no glue bonds, has avoided introducing other materials to cause the influence to the test result.

Alternatively, in the test chip, the chip is circular as a whole. The circular structure is adopted, so that the test unit bodies on the test unit bodies are distributed circularly, and therefore, when the chip is tested in vivo or in vitro, the relative position and orientation of each test unit body and the surrounding test environment are guaranteed to be similar, and experimental errors are reduced. Further, the diameter of the round chip is 1-20mm.

Alternatively, in the test chip, the substrate is spoke-shaped and includes a circular periphery and a plurality of spokes extending from the center of the circular periphery to the periphery. The number of the spokes can be flexibly designed according to actual needs so as to assemble different numbers of test unit bodies. The spoke-shaped structure contains more gaps, which is beneficial to the material exchange between the test unit body and the surrounding environment.

Alternatively, in the test chip, the spokes are fixedly connected to the circular periphery. The fixed connection is beneficial to improving the overall stability of the chip.

Alternatively, in the test chip, the spoke is provided with a bayonet matched and matched with the test unit body. The spoke can be used as a connecting site of the test unit bodies and plays a role in isolating adjacent test unit bodies, so that the environments of the single test unit bodies are relatively independent, and the mutual influence is avoided. Further, the number of the spokes is 3-8.

Alternatively, in the above test chip, the test unit body includes an outer ring test unit body and an inner ring test unit body, and after the assembly is completed, the outer ring test unit bodies are mutually spliced to form a chip outer ring, the inner ring test unit bodies are mutually spliced to form a chip inner ring, and the chip outer ring and the inner ring are mutually isolated by a gap structure isolation belt. The gap structure isolation belt divides the chip into two main areas of an inner ring and an outer ring, the outer ring can be used for testing the bone conduction effect of different unit bodies, and the inner ring can be used for evaluating the bone induction effect of different unit bodies. The gap structure isolation belt is used for isolating the bone conduction effect of the outer ring, and prevents the effect of the surrounding bone tissue on the bone induction result caused by the fact that the surrounding bone tissue grows into the inner part along the material in the in-vivo experiment. Therefore, what parameters are respectively beneficial to bone conduction and bone induction can be selected in the same chip. Further, the width of the gap structure isolation belt is 0.5-3mm.

Alternatively, in the above test chip, the specific test parameters corresponding to the test unit include, but are not limited to, parameters of phase composition, pore structure parameters, grain size, surface roughness, wettability, and the like of the material. In the use process, the test unit bodies corresponding to different test parameters can be designed according to actual test requirements. Alternatively, the single factor may be selected from the same test chip, or multiple factors may be selected simultaneously, and preferably the single factor is selected, that is, the test unit has a single key material parameter with different specifications.

Optionally, in the test chip, the material component used for manufacturing the test unit body is one or more of calcium silicate, tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, monocalcium phosphate and other biological ceramic materials

Alternatively, in the above test chip, the values of the test parameters corresponding to the test unit bodies may be completely different, or partially the same or completely the same, and the test unit bodies having the same values of the test parameters may be used as parallel tests.

In the above test chip, the test unit body is prepared by a 3D printing technology, and the values of the material components, pore structure parameters, physicochemical properties and other test parameters are precisely regulated and customized by the 3D printing technology.

Alternatively, in the above test chip, the substrate is made of one or more of calcium phosphate ceramic (CAP CERAMICS), pure titanium, and titanium alloy (Ti 6Al 4V), preferably a material with good biocompatibility, so as to minimize the influence on the test structure.

The preparation method of the modularized integrated bone regeneration repair capability test chip comprises the following steps: the substrate and the test unit body are prepared by adopting a 3D printing technology.

Alternatively, in the above preparation method, the 3D printing technology used for customizing the test chip is any one or more of 3D printing technologies such as three-dimensional inkjet printing (Three Dimension Printing,3 DP), selective laser sintering (SELECTIVE LASER SINTERING, SLS), stereolithography (Stereo lithographyAppearance, SLA), digital light processing (DIGITAL LIGHT processing, DLP), and the like.

Alternatively, in the above preparation method, the method includes the steps of:

(1) Determining the number of the test unit bodies and the corresponding specific test parameters according to the test requirement, and designing a model of the test unit bodies and the substrate;

(2) Preparing 3D printing raw materials of the substrate, and preparing corresponding 3D printing raw materials according to specific test parameters corresponding to each test unit body;

(3) Preparing a substrate and a test unit body corresponding to specific test parameters by adopting a 3D printing technology;

(4) And assembling the test unit body and the substrate to obtain the test chip.

Alternatively, in the above preparation method step (1), the corresponding unit bodies are divided according to the experimentally required tested parameters and positions, and models of the unit bodies and the substrate are designed in a computer.

Alternatively, in the step (2) of the preparation method, the raw materials corresponding to the different unit bodies, the photosensitive resin and the photoinitiator are uniformly mixed to obtain the printing ink with different material compositions.

Alternatively, in the above-described preparation method step (3), the configured printing ink is molded into the target unit body and substrate using a 3D printing apparatus.

Alternatively, in the above preparation method step (3), the different unit bodies and the substrate are sintered into bioceramics.

Application example 1

The application example researches the influence of components of different module materials on bone conductivity and bone inducibility. In this example, different Hydroxyapatite (HA) and tricalcium phosphate (TCP) in biphasic calcium phosphate ceramics (BCP) were selected as key test materials and their effects on bone conductivity and osteoinductive properties were studied. The proportions of the 4 BCPs used in the experiment were planned to be: 1) pure TCP, 2) HA/tcp=2/8, 3) HA/tcp=5/5, 4) pure HA. Thus the chip contains 4 bone conduction test units and 4 bone induction test units. Therefore, the capability difference of different TCP and HA ratios in the calcium phosphate on bone tissue regeneration and repair can be screened and detected.

The first step: 8 unit cells and a substrate model were designed in a computer (as shown in fig. 1-4). And a second step of: and uniformly mixing the four calcium phosphate powders, the photosensitive resin and the photoinitiator to obtain different printing inks. And a third step of: the configured printing ink was prepared into 8 kinds of unit bodies and a substrate using a 3D printing apparatus. Fourth step: and sintering the different unit bodies and the different base plates into calcium phosphate ceramics in a furnace, and assembling the unit bodies and the base plates to obtain the test chip. Fifth step: the assembled test chip is implanted into the skull defect part of the beagle, after the implantation is carried out for 2 months, the in-situ bone conduction effect of which BCP proportion is evaluated according to the new bone generation amount in 4 peripheral unit individuals is good, and the bone induction effect of which BCP proportion is evaluated according to the new bone generation amount of 4 unit bodies in the inner layer is best. Through the method, the expected parameters can be efficiently screened, on one hand, the efficiency of improving the number of animals is greatly reduced, and the adverse effects caused by individual differences of the animals can be reduced. In addition, the comparison of the experiment is more visual.

Application example 2

In this application example, the influence of the components of different module materials on the bone conductivity and the bone inducibility was studied. In this example, different Hydroxyapatite (HA) and tricalcium phosphate (TCP) in biphasic calcium phosphate ceramics (BCP) were selected as key test materials and their effects on bone conductivity and osteoinductive properties were studied. The other steps of the present application example are the same as those of application example 1, except that: the proportions of 6 BCPs used in the experiments were: 1) pure TCP, 2) HA/tcp=2/8, 3) HA/tcp=3/7, 4) HA/tcp=4/6, 5) HA/tcp=5/5, 6) pure HA. The number of spokes in the chip was therefore 6, comprising 6 osteoinductive test units and 6 osteoinductive test units. Therefore, the capability difference of different TCP and HA ratios in the calcium phosphate on bone tissue regeneration and repair can be screened and detected.

Application example 3

In this application example, the influence of the components of different module materials on the bone conductivity and the bone inducibility was studied. In this example, different Hydroxyapatite (HA) and tricalcium phosphate (TCP) in biphasic calcium phosphate ceramics (BCP) were selected as key test materials and their effects on bone conductivity and osteoinductive properties were studied. The other steps of the present application example are the same as those of application example 1, except that: the proportions of the 4 BCPs used in the experiment were planned to be: 1) Pure TCP, 2) TCP/Ca ₂SiO₄＝3/7,3)TCP/Ca₂SiO₄ =4/6, 4) pure Ca ₂SiO₄. Thus the chip contains 4 bone conduction test units and 4 bone induction test units. Therefore, the capability difference of different ratios of TCP and Ca ₂SiO₄ in the calcium phosphate to regeneration and repair of bone tissues can be screened and detected.

Application example 4

In this application example, the influence of the components of different module materials on the bone conductivity and the bone inducibility was studied. In this example, different Hydroxyapatite (HA) and tricalcium phosphate (TCP) in biphasic calcium phosphate ceramics (BCP) were selected as key test materials and their effects on bone conductivity and osteoinductive properties were studied. The other steps of the present application example are the same as those of application example 1, except that: the proportions of the 4 BCPs used in the experiment were planned to be: 1) Pure HA, 2) HA/Ca ₂SiO₄＝3/7,3)HA/Ca₂SiO₄ =4/6, 4) pure Ca ₂SiO₄, only 4 bone conduction test units were contained in the chip. Therefore, the capability difference of different HA and Ca ₂SiO₄ ratios in the calcium phosphate on bone tissue regeneration and repair can be screened and detected.

Application example 5

In this application example, the effect of 4 different bioceramic grains on bone conduction and bone induction was tested. In this example, hydroxyapatite was selected as a test target material, and the other steps of this example were the same as those of example 1 except that: 8 hydroxyapatite units of different grain sizes (ceramic grain size 1-8um was prepared by sintering process, screening grain size step size 1 um) were prepared in a similar manner to application example 1 and assembled with a substrate, and the chip contained 8 bone conduction test units and 8 bone induction test units. In the skull of the goat implanted, after 2 months of implantation, the osteogenesis behaviors of different unit bodies are respectively analyzed, so that the influences of different hydroxyapatite grain sizes on bone conduction and bone induction phenomena can be screened and detected.

Application example 6

In this application example, the effect of 4 different bioceramic grains on bone conduction and bone induction was tested. In this example, hydroxyapatite was selected as a test object material, and 4 assembly units were required for the inner and outer peripheries, respectively, in the same manner as in application example 1. The other steps of the present application example are the same as those of application example 1, except that: 8 hydroxyapatite units of different grain sizes (ceramic grain size 10-50um prepared by sintering process, screening grain size step size 5 um) were prepared in a similar manner to application example 1 and assembled with a substrate. In the skull of the goat implanted, after 2 months of implantation, the osteogenesis behaviors of different unit bodies are respectively analyzed, so that the influences of different hydroxyapatite grain sizes on bone conduction and bone induction phenomena can be screened and detected.

Application example 7

In this application example, the influence of 4 kinds of macroscopic porous structures on the bone regeneration ability and the influence of the porous structure on the bone inducibility were tested. Unlike the above application example 1, the material parameters to be examined in the present application example are the effects of the macroscopic porous structure. Therefore, first, 4 peripheral unit bodies with different porous structures and 4 inner unit bodies with different porous structures are designed in a computer. The other steps of the present application example are the same as those of application example 1, except that: the 4 macroscopic porous structures are designed to be 100um, 200um, 300um and 400um, and the porous structure test chip is prepared and assembled in the manner of application example 1. Implanted into target animals, the effect of the macro-porous size on bone repair can be screened and detected by analyzing the osteogenic behaviors of different unit bodies.

Application example 8

In this application example, the influence of 4 kinds of macroscopic porous structures on the bone regeneration ability and the influence of the porous structure on the bone inducibility were tested. Unlike the above application example 1, the material parameters to be examined in the present application example are the effects of the macroscopic porous structure. Therefore, first, 4 peripheral unit bodies with different porous structures and 4 inner unit bodies with different porous structures are designed in a computer. The other steps of this application example are the same as those of application example 7, except that: 4 kinds of macroscopic porous structures are designed to be 500um, 600um, 700um and 800um, and the porous structure test chip is prepared and assembled in the manner of application example 1. Implanted into target animals, the effect of the macro-porous size on bone repair can be screened and detected by analyzing the osteogenic behaviors of different unit bodies.

Application example 9

In this application example, it is planned to examine the effect of 5 (silver, strontium, magnesium, copper, silicon) element-doped tricalcium phosphate on bone conductivity, and the effect of these 5 element doping on bone regeneration ability. In comparison with the above-described application example 1, in the present application example, 5 external different element doped unit bodies and 5 internal different element doped unit bodies are required. Therefore, firstly, 5 tricalcium phosphate powder doped with different elements is adopted to prepare the 3D printing ink. Thereafter, 10 unit bodies and corresponding substrates were prepared and assembled into test chips according to the manner provided in application example 1. The other steps of the present application example are the same as those of application example 1, except that: in pure tricalcium phosphate, 5 (silver, strontium, magnesium, copper, silicon) elements are synthesized and doped, and the doping amount of each element is 1 weight percent. The components with different material compositions are customized through printing, the number of spokes in the chip is 5, the spokes are finally implanted into a target animal after assembly, and the influences of doping of different elements on bone repair can be screened and detected through analyzing the osteogenesis behaviors of different unit bodies.

Application example 10

In this application example, it is planned to examine the effect of 5 (silver, strontium, magnesium, copper, silicon) element-doped tricalcium phosphate on bone conductivity, and the effect of these 5 element doping on bone regeneration ability. In comparison with the above-described application example 1, in the present application example, 5 external different element doped unit bodies and 5 internal different element doped unit bodies are required. Therefore, firstly, 5 tricalcium phosphate powder doped with different elements is adopted to prepare the 3D printing ink. Thereafter, 10 unit bodies and corresponding substrates were prepared and assembled into test chips according to the manner provided in application example 1. The other steps of this application example are the same as those of application example 9, except that: in pure tricalcium phosphate, 5 (silver, strontium, magnesium, copper, silicon) elements are synthesized and doped, and the doping amount of each element is 2 weight percent. The components with different material compositions are customized through printing, the components are finally implanted into a target animal after being assembled, and the influences of doping of different elements on bone repair can be screened and detected through analyzing the osteogenesis behaviors of different unit bodies.

Application example 11

In this application example, it is planned to examine the effect of 5 (silver, strontium, magnesium, copper, silicon) element-doped tricalcium phosphate on bone conductivity, and the effect of these 5 element doping on bone regeneration ability. In comparison with the above-described application example 1, in the present application example, 5 external different element doped unit bodies and 5 internal different element doped unit bodies are required. Therefore, firstly, 5 tricalcium phosphate powder doped with different elements is adopted to prepare the 3D printing ink. Thereafter, 10 unit bodies and corresponding substrates were prepared and assembled into test chips according to the manner provided in application example 1. The other steps of this application example are the same as those of application example 9, except that: in pure tricalcium phosphate, 5 (silver, strontium, magnesium, copper, silicon) elements are synthesized and doped, and the doping amount of each element is 3 weight percent. The components with different material compositions are customized through printing, the components are finally implanted into a target animal after being assembled, and the influences of doping of different elements on bone repair can be screened and detected through analyzing the osteogenesis behaviors of different unit bodies.

The foregoing is merely a preferred embodiment of the present invention, which is intended to be illustrative and not limiting; it will be appreciated by those skilled in the art that many variations, modifications and even equivalent changes may be made thereto, within the spirit and scope of the invention as defined in the appended claims, but are to be accorded the full scope of the invention.

Claims (4)

1. The modularized integrated bone regeneration repair capability test chip is characterized by comprising a substrate and a plurality of test unit bodies, wherein the different test unit bodies are isolated from each other; the substrate is used for integrating and fixing the test unit bodies, each test unit body corresponds to a specific test parameter, and a mutually matched structure is arranged between the test unit bodies and the substrate and used for guaranteeing the stability of the chip after the unit bodies and the substrate are assembled; the test unit body comprises an outer ring test unit body and an inner ring test unit body, after the assembly is completed, the outer ring test unit bodies are mutually spliced to form a chip outer ring, the inner ring test unit bodies are mutually spliced to form a chip inner ring, and the chip outer ring and the inner ring are mutually isolated through a gap structure isolation belt;

The whole chip is round;

The substrate is spoke-shaped and comprises a round periphery and a plurality of spokes extending from the center of the round periphery to the periphery, and bayonets matched and matched with the test unit body are arranged on the spokes;

The specific test parameters corresponding to the test unit body comprise one or more of material phase components, pore structure parameters, material grain size, surface roughness and wettability of the material.

2. A method of manufacturing a modular integrated bone regeneration repair capability test chip according to claim 1, wherein the substrate and the test unit are manufactured using a 3D printing technique.

3. The preparation method according to claim 2, characterized by comprising the steps of:

(1) Determining the number of the test unit bodies and the corresponding specific test parameters according to the test requirement, and designing a model of the test unit bodies and the substrate;

(2) Preparing 3D printing raw materials of the substrate, and preparing corresponding 3D printing raw materials according to specific test parameters corresponding to each test unit body;

(3) Preparing a substrate and a test unit body corresponding to specific test parameters by adopting a 3D printing technology;

(4) And assembling the test unit body and the substrate to obtain the test chip.

4. Use of the modular integrated bone regeneration repair capability test chip according to claim 1, for high throughput screening of advanced bone tissue regeneration biomaterials.