Plasma matrix bone block, guided bone regeneration composite material and preparation method thereof

Abstract

The invention relates to the technical field of medical materials, in particular to a plasma matrix bone block, a guided bone regeneration composite material and a preparation method thereof. According to the plasma matrix bone block provided by the invention, a plasma matrix and a bone repair material are compounded by utilizing a rolling-pressing scheme to construct a densified bone block core, the crosslinking degree of internal fibers is remarkably improved, and a guided bone regeneration composite material obtained by organically compounding the densified bone block core with a plasma matrix membrane can form a complete biological barrier; and when the material is applied to bone defect repair, operation steps can be simplified, a bionic microenvironment is established, vascularization and osteogenic differentiation are promoted, and an ideal solution with mechanical support, space maintenance and biological activity is provided for regeneration and repair of complex bone defects.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a plasma matrix bone block, a guided bone regeneration composite material and a preparation method thereof. Background Art

[0002] Bone tissue defect repair is an important clinical challenge faced in oral implantology, maxillofacial surgery and orthopedic surgery. Since its introduction, guided bone tissue regeneration technology has become the mainstream method to solve bone deficiency. Traditional guided bone tissue regeneration technology relies on collagen membrane as a barrier to isolate soft tissue cells, while combining bone graft materials to promote osteogenesis. However, existing technologies have significant defects: first, collagen membranes need to be purchased separately and are expensive, and their degradation rate is difficult to accurately match the bone regeneration cycle; second, autologous bone transplantation causes donor site trauma, and granular xenogeneic bone or artificial bone materials often cause structural collapse due to insufficient mechanical strength after transplantation.

[0003] In recent years, plasma matrix has received widespread attention due to its excellent biocompatibility and repair-promoting ability. Some studies have disclosed a method for preparing fibrin scaffolds by freeze-drying, but it is difficult to meet the needs of repairing bone defects in the load-bearing area. Some scholars have also proposed to prepare multilayer plasma matrix membranes by centrifugation, but the problem of the integration of membrane-bone composite structures has not been solved. Therefore, existing plasma matrix-related products generally have the problem of single function - either focusing on bone conductivity but lacking barrier function, or having barrier properties but unable to provide a three-dimensional osteogenic microenvironment. What is more noteworthy is that the existing technology mostly adopts a split design of "membrane combined with bone block", and the membrane and bone material need to be fixed separately during the operation, which not only prolongs the operation time, but also causes micro-motion and infection risks due to loose interface bonding.

[0004] Furthermore, optimizing the mechanical properties of the plasma matrix remains a technical challenge at the materials science level. The team's early research found that combining solid plasma matrix membrane fragments, liquid plasma matrix, and bone repair materials to prepare plasma matrix bone blocks significantly improved their mechanical strength and molding effects. However, in actual clinical use, further cutting of the plasma matrix bone blocks often revealed insufficient fiber cross-linking within the blocks, with the bone powder remaining granular, severely impacting the user experience and performance of the plasma matrix bone blocks. Summary of the Invention

[0005] To address the above technical issues, the present invention provides a plasma matrix bone block, a guided bone regeneration composite material, and a preparation method thereof. The plasma matrix bone block provided by the present invention utilizes a rolling-pressing method to composite plasma matrix and bone repair material to construct a densified bone block core, significantly improving the internal fiber cross-linking degree. The resulting guided bone regeneration composite material, which is organically combined with a plasma matrix membrane, can form a complete biological barrier. Application to bone defect repair can simplify surgical procedures, establish a biomimetic microenvironment, and promote vascularization and osteogenic differentiation, providing an ideal solution for the regenerative repair of complex bone defects that combines mechanical support, spatial maintenance, and biological activity.

[0006] In a first aspect, the present invention provides a method for preparing a plasma matrix bone block, the method comprising the following steps:

[0007] (1) impregnating a monolayer of dispersed bone repair material with a mixture of a liquid plasma matrix obtained by blood centrifugation and a leukocyte-rich intermediate layer, allowing the mixture to solidify, and pressing the mixture to obtain a plasma matrix bone block precursor material;

[0008] (2) adding a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer to at least one surface of the plasma matrix bone block precursor material, winding and shaping the material along the length direction to obtain the plasma matrix bone block.

[0009] The present invention utilizes a rolling-pressing scheme to composite plasma matrix and bone repair material to construct a densified bone core, which can significantly improve the internal fiber cross-linking degree. The liquid plasma matrix and the leukocyte-rich intermediate layer can play a good cross-linking role on the basis of excellent biocompatibility and repair-promoting ability. After the single-layer dispersed bone repair material is impregnated, solidified and pressed, a plasma matrix bone precursor material with good cross-linking effect can be obtained. On this basis, the liquid plasma matrix and the leukocyte-rich intermediate layer are again used as cross-linking agents to coil the precursor material. The internal fiber cross-linking degree is significantly improved through multi-stage composite superposition. The cylindrical plasma matrix bone block obtained by winding can be shaped according to actual clinical needs. For example, its size can be adjusted according to the morphology and size of the patient's defect area to obtain the final required plasma matrix bone block.

[0010] As a preferred technical solution of the present invention, the thickness of the plasma matrix bone block precursor material is greater than 1 mm, preferably 1-3 mm, such as 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, etc.

[0011] As a preferred technical solution of the present invention, the pressing pressure is 0.5-2N, such as 0.5N, 1N, 1.5N, 2N, etc., and the pressing time is 10-300s, such as 10s, 50s, 100s, 150s, 200s, 250s, 300s, etc.

[0012] As a preferred technical solution of the present invention, the bone repair material includes any one or more of autologous bone, allogeneic bone, xenogeneic bone and artificial bone.

[0013] As a preferred technical solution of the present invention, step (1) is:

[0014] A mixture of liquid plasma matrix and leukocyte-rich middle layer is dripped onto the surface of a single-layer dispersed bone repair material, and allowed to stand and solidify to obtain a primary composite material. The material is turned over, and a mixture of liquid plasma matrix and leukocyte-rich middle layer is dripped onto the other surface, and allowed to stand and solidify to obtain a secondary composite material. The material is pressed to obtain a plasma matrix bone block precursor material.

[0015] The method of impregnating the monolayer dispersed bone repair material with the mixture of the liquid plasma matrix and the leukocyte-rich intermediate layer of the present invention is preferably to drop the mixture on both surfaces of the monolayer dispersed bone repair material respectively, so that the mixture can be distributed more evenly to form a dense cross-linked plasma matrix bone block precursor material.

[0016] As a preferred technical solution of the present invention, the thickness of the primary composite material is 1 mm or more, preferably 3-10 mm, such as 3 mm, 5 mm, 8 mm, 10 mm, etc.

[0017] As a preferred technical solution of the present invention, the thickness of the secondary composite material is 2 mm or more, preferably 6-20 mm, for example, 6 mm, 8 mm, 10 mm, 12 mm, 14 mm, 16 mm, 18 mm, 20 mm, etc.

[0018] As a preferred technical solution of the present invention, the ratio of the mass of the bone repair material to the total volume of the mixed solution of the liquid plasma matrix and the leukocyte-rich intermediate layer is 0.25g:3-30mL, for example, 0.25g:3mL, 0.25g:5mL, 0.25g:10mL, 0.25g:15mL, 0.25g:20mL, 0.25g:25mL, 0.25g:30mL, etc.

[0019] It is understood that the total volume of the mixture of the liquid plasma matrix and the leukocyte-rich intermediate layer refers to the sum of the total volumes of the mixture of the liquid plasma matrix and the leukocyte-rich intermediate layer used in the entire process of the plasma matrix bone block preparation method of the present invention.

[0020] In a second aspect, the present invention provides a plasma matrix bone block prepared by the preparation method described in the first aspect.

[0021] As a preferred technical solution of the present invention, based on the total weight of the plasma matrix bone block as 100%, the content of the bone repair material is 8-45%, for example, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, etc.

[0022] In a third aspect, the present invention provides a use of the plasma matrix bone block described in the second aspect in a bone defect repair material.

[0023] In a fourth aspect, the present invention provides a guided bone regeneration composite material, which comprises the plasma matrix bone block described in the third aspect and a plasma matrix membrane composited on part of its surface, and further comprises a cross-linked layer rich in plasma matrix and leukocytes between the plasma matrix bone block and the plasma matrix membrane.

[0024] The guided bone regeneration composite material provided by the present invention has high cross-linking density and high strength and combines osteoconduction, osteoinduction, bone regeneration and soft tissue cell barrier functions. Compared with traditional guided bone tissue regeneration surgery, the guided bone regeneration composite material provided by the present invention does not require the additional use of collagen membrane, is more economical for patients, and is convenient for surgeons to operate. At the same time, it has good biosafety, solves the problems of insufficient fiber cross-linking, low strength, and single function of traditional plasma matrix bone blocks, and provides an integrated solution for the regeneration and repair of bone tissue defects.

[0025] The guided bone regeneration composite material provided by the present invention includes the plasma matrix bone block described in the third aspect and a plasma matrix membrane composited on a portion of its surface. It can be understood that since the guided bone regeneration composite material of the present invention is used for regenerative repair of bone tissue defects, the plasma matrix membrane replaces the collagen membrane in the traditional solution. Therefore, the plasma matrix membrane is only composited on a portion of the surface of the plasma matrix bone block, and the composite contact surface can be selected according to actual needs. Moreover, when used for bone defect repair, the plasma matrix membrane serves as the near-soft tissue surface. In order to form a complete biological barrier, the plasma matrix membrane extends more than 2 mm on all sides of the composite contact surface.

[0026] As a preferred technical solution of the present invention, the thickness of the plasma matrix membrane is 0.5-2 mm, for example, 0.5 mm, 1 mm, 1.5 mm, 2 mm, etc.

[0027] In a fifth aspect, the present invention provides a method for preparing the composite material for guided bone regeneration according to the fourth aspect, the preparation method comprising:

[0028] (1) Centrifuging the blood to obtain a solid plasma matrix, heating and pressurizing it to obtain a heat-dense plasma matrix membrane;

[0029] (2) using the mixed solution of the liquid plasma matrix and the white blood cell-rich intermediate layer obtained by centrifugation of blood as a crosslinking agent to crosslink and compound the thermally-densified plasma matrix membrane and the plasma matrix bone block, to obtain the guided bone regeneration composite material;

[0030] The plasma matrix bone block is the plasma matrix bone block of the second aspect.

[0031] The preparation method provided by the application performs thermal densification treatment on the plasma matrix, can realize crosslinking of collagen fibers of the plasma matrix membrane, effectively improve the internal fiber density, prolong the degradation time of the plasma matrix membrane, and retain more than 90% of the growth factor activity; meanwhile, a "membrane-bone" integrated composite structure is created, the membrane and the bone interface are crosslinked through the liquid plasma matrix and the white blood cell-rich intermediate layer, and the membrane layer extends more than 2mm around the composite contact surface, forming a complete biological barrier. The guided bone regeneration composite material prepared by the method simplifies the surgical steps when repairing bone defects, and further promotes vascularization and osteogenic differentiation by establishing a biomimetic microenvironment. The application provides an ideal solution for the regeneration and repair of complex bone defects by combining material modification and structural innovation, which has mechanical support, space maintenance and biological activity, and relieves the urgent need for low-cost and high-efficiency regenerative medicine products in the clinic.

[0032] As a preferred technical solution of the application, the temperature during heating is 65-90℃, such as 65℃, 70℃, 75℃, 80℃, 85℃, 90℃, etc., preferably 70-80℃.

[0033] As a preferred technical solution of the application, the pressure during pressing is 5-20N, such as 5N, 10N, 15N, 20N, etc., and the pressing time is 0.5-5min, such as 0.5min, 1min, 2min, 3min, 4min, 5min, etc.

[0034] The non-heated surface of the thermally-densified plasma matrix membrane obtained by the application is compounded with the plasma matrix bone block.

[0035] The technical solution provided by the embodiments of the application has the following advantages compared with the prior art:

[0036] 1. The plasma matrix bone block provided by the application uses a rolling-pressing scheme to compound and construct a densified bone block core by using plasma matrix and bone repair material, significantly improves the internal fiber crosslinking degree, and the guided bone regeneration composite material obtained by organically compounding the plasma matrix membrane can form a complete biological barrier, which can simplify the surgical steps, establish a biomimetic microenvironment, and promote vascularization and osteogenic differentiation when applied to bone defect repair, providing an ideal solution for the regeneration and repair of complex bone defects, which has mechanical support, space maintenance and biological activity.

[0037] 2. The guided bone regeneration composite material provided by the present invention has high cross-linking density and high strength and combines osteoconduction, osteoinduction, bone regeneration and soft tissue cell barrier functions. Compared with traditional guided bone tissue regeneration surgery, the guided bone regeneration composite material provided by the present invention does not require the additional use of collagen membrane, is more economical for patients, and is convenient for surgeons to operate. At the same time, it has good biosafety and solves the problems of insufficient fiber cross-linking, low strength and single function of traditional plasma matrix bone blocks, providing an integrated solution for the regeneration and repair of bone tissue defects. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0039] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0040] Figure 1 This is a structural diagram of the plasma matrix bone block precursor material in Preparation Example 1 of the present invention. DETAILED DESCRIPTION

[0041] In order to more clearly understand the above-mentioned objectives, features and advantages of the present invention, the scheme of the present invention will be further described below. It should be noted that, in the absence of conflict, the embodiments of the present invention and the features therein can be combined with each other.

[0042] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein; it is obvious that the embodiments in the specification are only part of the embodiments of the present invention, rather than all the embodiments.

[0043] Preparation Example 1

[0044] This preparation example provides a plasma matrix bone block and a preparation method thereof, the preparation method comprising the following steps:

[0045] (1) Collect 30 mL of human blood using three liquid plasma matrix blood collection tubes (10 mL per tube), and quickly centrifuge at 700 g for 8 minutes to obtain a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer;

[0046] (2) monolayer dispersion of 0.25 g of granular calf bone powder bone repair material;

[0047] (3) adding a mixture of liquid plasma matrix and leukocyte-rich intermediate layer obtained from a blood collection tube (about 5 mL) dropwise and allowing to solidify to obtain a primary composite material with a thickness of about 5 mm;

[0048] (4) Turn the primary composite material over and add a mixture of liquid plasma matrix and leukocyte-rich intermediate layer (about 5 mL) obtained from another blood collection tube. Let it stand and solidify to obtain a secondary composite material with a thickness of about 10 mm.

[0049] (5) Using a plasma matrix presser to densify the secondary composite material, the pressure is 1N, and the pressing time is 2min, to obtain a plasma matrix bone block precursor material with a thickness of about 2mm. The structure of the plasma matrix bone block precursor material is as follows: Figure 1 As shown;

[0050] (6) A mixture of liquid plasma matrix and a leukocyte-rich intermediate layer (about 5 mL) obtained from another blood collection tube is dripped onto one surface of the plasma matrix bone block precursor material, and the material is rolled along the length direction to shape the material to obtain the plasma matrix bone block.

[0051] Preparation Example 2

[0052] This preparation example provides a plasma matrix bone block and a preparation method thereof, the preparation method comprising the following steps:

[0053] (1) 60 mL of human blood was collected using 6 liquid plasma matrix blood collection tubes (10 mL per tube), and the blood was immediately centrifuged at 700 g for 8 minutes in a horizontal centrifuge to obtain a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer;

[0054] (2) monolayer dispersion of 0.25 g of granular allogeneic bone repair material;

[0055] (3) adding about 10 mL of the mixture of the obtained liquid plasma matrix and the leukocyte-rich intermediate layer dropwise and allowing to solidify to obtain a primary composite material with a thickness of about 10 mm;

[0056] (4) turning the primary composite material over, and adding about 10 mL of the mixture of the obtained liquid plasma matrix and the leukocyte-rich intermediate layer dropwise again, and allowing it to solidify to obtain a secondary composite material with a thickness of about 20 mm;

[0057] (5) using a plasma matrix press to densify the secondary composite material at a pressure of 0.5 N and a pressing time of 5 min to obtain a plasma matrix bone block precursor material with a thickness of approximately 3 mm;

[0058] (6) About 10 mL of a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer is dripped onto one surface of the plasma matrix bone block precursor material, and the mixture is rolled along the length direction to shape the mixture, thereby obtaining the plasma matrix bone block.

[0059] Preparation Example 3

[0060] This preparation example provides a plasma matrix bone block and a preparation method thereof, the preparation method comprising the following steps:

[0061] (1) 10 mL of human blood was collected using a liquid plasma matrix blood collection tube and immediately centrifuged at 700 g for 8 minutes in a horizontal centrifuge to obtain a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer;

[0062] (2) monolayer dispersion of 0.25 g of granular artificial bone repair material;

[0063] (3) adding approximately 1 mL of a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer obtained from a blood collection tube, and allowing the mixture to solidify to obtain a primary composite material with a thickness of approximately 1 mm;

[0064] (4) turning the primary composite material over, and adding about 1 mL of the mixture of the liquid plasma matrix and the leukocyte-rich intermediate layer obtained from the blood collection tube, and allowing it to solidify to obtain a secondary composite material with a thickness of about 2 mm;

[0065] (5) using a plasma matrix press to densify the secondary composite material at a pressure of 2 N and a pressing time of 10 s to obtain a plasma matrix bone block precursor material with a thickness of approximately 1 mm;

[0066] (6) About 1 mL of a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer is dripped onto one surface of the plasma matrix bone block precursor material, and the mixture is rolled along the length direction to shape the mixture, thereby obtaining the plasma matrix bone block.

[0067] Example 1

[0068] This embodiment provides a composite material for guided bone regeneration and a preparation method thereof, the preparation method comprising the following steps:

[0069] (1) Collect 10 mL of human liquid whole blood using a liquid plasma matrix blood collection tube, quickly place the blood sample in a horizontal centrifuge and centrifuge at 700 g for 8 minutes to obtain a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer;

[0070] Collect 10 mL of human blood using a solid plasma matrix blood collection tube, quickly centrifuge at 700 g for 8 minutes to obtain a solid plasma matrix;

[0071] (2) The plasma matrix incubation platform preheats the mold to 75°C, the solid plasma matrix is ​​transferred into the mold, and the plasma matrix press is used to press at 20N pressure and 75°C for 5 minutes to obtain a heat-dense plasma matrix membrane with a thickness of approximately 0.5 mm.

[0072] (3) A mixture of liquid plasma matrix and a leukocyte-rich intermediate layer is added dropwise to the non-heated side of the heat-densified plasma matrix membrane, and the plasma matrix bone block prepared in Example 1 is placed thereon, ensuring that the membrane extends more than 2 mm around the composite contact surface with the bone block, thereby obtaining the guided bone regeneration composite material.

[0073] Example 2

[0074] This embodiment provides a composite material for guided bone regeneration and a preparation method thereof. The preparation method is the same as that of Example 1, except that step (2) in this embodiment is:

[0075] The plasma matrix incubation platform was preheated to 70°C, the solid plasma matrix was transferred into the mold, and the plasma matrix press was used to press the mold at 5N pressure and 70°C for 0.5 min to obtain a thermally dense plasma matrix membrane with a thickness of about 2 mm.

[0076] Example 3

[0077] This embodiment provides a composite material for guided bone regeneration and a preparation method thereof. The preparation method is the same as that of Example 1, except that step (2) in this embodiment is:

[0078] The plasma matrix incubation platform was preheated to 80°C, the solid plasma matrix was transferred into the mold, and the plasma matrix press was used to press the mold at 20N pressure and 80°C for 0.5min to obtain a heat-dense plasma matrix membrane with a thickness of 1mm.

[0079] Example 4

[0080] This embodiment provides a guided bone regeneration composite material and a preparation method thereof. The preparation method is the same as that of Example 1. The difference from Example 1 is that in step (3) of this embodiment, the plasma matrix bone block is replaced with the plasma matrix bone block prepared in Preparation Example 2.

[0081] Example 5

[0082] This embodiment provides a guided bone regeneration composite material and a preparation method thereof. The preparation method is the same as that of Example 1. The difference from Example 1 is that in step (3) of this embodiment, the plasma matrix bone block is replaced with the plasma matrix bone block prepared in Preparation Example 3.

[0083] Comparative Example 1

[0084] This comparative example provides a traditional plasma matrix bone block composite material and a preparation method thereof, wherein the preparation method comprises the following steps:

[0085] (1) using 2 glass blood collection tubes to collect 10 mL of liquid whole blood sample respectively, and using 1 plastic blood collection tube to collect 10 mL of liquid whole blood sample, wherein the glass blood collection tube is used to prepare the solid-state plasma matrix, and the plastic blood collection tube is used to prepare the liquid-state plasma matrix;

[0086] The collected whole blood sample is quickly placed in a horizontal centrifuge to centrifuge at 700 g for 8 minutes to obtain the liquid-state plasma matrix and the solid-state plasma matrix respectively;

[0087] (2) using a solid-state plasma matrix press to press the solid-state plasma matrix to obtain 2 solid-state plasma matrix films with a thickness of 2 mm, which are cut into solid-state plasma matrix particles with a particle size of 1-2 mm;

[0088] (3) mixing the solid-state plasma matrix particles and 0.5 g of calf bone powder, and injecting into the mixed liquid of 5 mL of liquid-state plasma matrix and leukocyte-rich intermediate layer, and obtaining the traditional plasma matrix bone block composite material after the mixed liquid is solidified.

[0089] Performance test

[0090] 1. The mechanical properties of the guided bone regeneration composite materials prepared in Examples 1-5 and the traditional plasma matrix bone block composite material prepared in Comparative Example 1 are tested.

[0091] Compression test test method: the composite materials obtained in the examples and comparative examples are respectively shaped into cubic blocks with a size of 5x5x5mm. Adjust and calibrate the compression strain tester to ensure the stability and accuracy of the equipment. Set the loading rate to 0.5mm / s and the maximum loading force to 100N. Place the composite material on the test table and fix and adjust to ensure the stability of the sample. Start the compression strain tester and monitor and record the test data in real time, including loading force, displacement and deformation, etc.

[0092] The test results are shown in Table 1 below:

[0093] Table 1

[0094] project Displacement (mm) Deformation (%) Loading force (N) Example 1 3 60 21.6 Example 2 3 60 8.7 Example 3 3 60 14.9 Example 4 3 60 17.3 Example 5 3 60 6.5 Comparative Example 1 3 60 5.2

[0095] As can be seen from the results in Table 1, the overall mechanical strength of the guided bone regeneration composite material provided by the application, especially the ability to resist compression, is significantly higher than that of the traditional plasma matrix bone block composite material.

[0096] From the comparison of Examples 1-5, it can be found that the strength of Example 2 is relatively low due to the relatively thick heat-densified plasma matrix film, and it is more prone to deformation when resisting the loading force; and Example 5 is also more prone to displacement because it is prepared using only a small amount of liquid-state plasma matrix and leukocyte-rich intermediate layer mixed liquid, and the internal cross-linking degree is relatively weak.

[0097] 2. The biological properties of the guided bone regeneration composite materials prepared in Examples 1-5 and the traditional plasma matrix bone block composite material prepared in Comparative Example 1 were tested.

[0098] Barrier function testing method: The composite materials obtained in Example 1 and Comparative Example 1 were each processed into a 10 × 10 × 5 mm size. In Example 1, 50 μL of crystal violet stain was added to the membrane side of the guided bone regeneration composite. In Comparative Example 1, 50 μL of crystal violet stain was added to either side of the plasma-matrix-bone composite. After 10 minutes, a vertical section was made through the center of the crystal violet drop, and the depth of the crystal violet stain was recorded.

[0099] It can be found that Example 1 did not penetrate into the underlying plasma matrix bone block, while the height of the plasma matrix bone block penetrated by Comparative Example 1 was about 3 mm, indicating that the heat-dense plasma matrix membrane of the present invention has a potential barrier function and can play a certain role in isolating soft tissue cells when applied to guided bone regeneration surgery.

[0100] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article, or device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or device. In the absence of further limitations, an element defined by the phrase "comprising a ..." does not exclude the presence of other identical elements in the process, method, article, or device comprising the element.

[0101] The foregoing description is intended only to provide specific embodiments of the present invention, which will enable those skilled in the art to understand and implement the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not intended to be limited to the embodiments described herein, but is to be construed in the widest manner consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing plasma matrix bone blocks, characterized in that: The preparation method comprises the following steps: (1) impregnating a monolayer of dispersed bone repair material with a mixture of a liquid plasma matrix obtained by blood centrifugation and a leukocyte-rich intermediate layer, allowing the mixture to solidify, and pressing the mixture to obtain a plasma matrix bone block precursor material; (2) adding a mixture of liquid plasma matrix and a leukocyte-rich intermediate layer to at least one surface of the plasma matrix bone block precursor material, winding and shaping the material along the length direction to obtain the plasma matrix bone block.

2. The preparation method according to claim 1, characterized in that The thickness of the plasma matrix bone block precursor material is greater than 1 mm, preferably 1-3 mm; And / or, the pressing pressure is 0.5-2N and the pressing time is 10-300s; And / or, the bone repair material includes any one or more of autologous bone, allogeneic bone, xenogeneic bone and artificial bone.

3. The preparation method according to claim 1 or 2, characterized in that The step (1) is: A mixture of a liquid plasma matrix and a leukocyte-rich intermediate layer is dripped onto the surface of a monolayer dispersed bone repair material, and allowed to solidify to obtain a primary composite material. The material is turned over, and a mixture of a liquid plasma matrix and a leukocyte-rich intermediate layer is dripped onto the other surface, and allowed to solidify to obtain a secondary composite material. The material is pressed to obtain a plasma matrix bone block precursor material. Preferably, the thickness of the primary composite material is 1 mm or more, preferably 3-10 mm; Preferably, the thickness of the secondary composite material is 2 mm or more, preferably 6-20 mm.

4. The preparation method according to any one of claims 1 to 3, characterized in that The ratio of the mass of the bone repair material to the total volume of the mixed solution of the liquid plasma matrix and the leukocyte-rich intermediate layer is 0.25 g:3-30 mL.

5. The plasma matrix bone block prepared by the preparation method according to any one of claims 1 to 4.

6. Use of the plasma matrix bone block according to claim 5 in bone defect repair materials.

7. A composite material for guided bone regeneration, characterized in that: The guided bone regeneration composite material comprises the plasma matrix bone block according to claim 5 and a plasma matrix membrane composited on a portion of the surface thereof, and further comprises a cross-linking layer rich in plasma matrix and leukocytes between the plasma matrix bone block and the plasma matrix membrane.

8. The composite material for guided bone regeneration according to claim 7, characterized in that The thickness of the plasma matrix membrane is 0.5-2 mm.

9. The method for preparing the composite material for guided bone regeneration according to claim 7 or 8, characterized in that: The preparation method comprises: (1) Centrifuging the blood to obtain a solid plasma matrix, heating and pressurizing it to obtain a heat-dense plasma matrix membrane; (2) using a mixture of liquid plasma matrix obtained by blood centrifugation and a leukocyte-rich intermediate layer as a crosslinking agent to crosslink and composite the heat-dense plasma matrix membrane and the plasma matrix bone block to obtain the guided bone regeneration composite material; The plasma matrix bone block is the plasma matrix bone block according to claim 5.

10. The preparation method according to claim 9, characterized in that The heating temperature is 65-90°C, preferably 70-80°C; And / or, the pressure during pressurization is 5-20N, and the pressing time is 0.5-5min.

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