Porous granule with high filling property

Abstract

The utility model provides a porous granular body with high filling property, which comprises a closed body with a continuous curved surface or a combination of a curved surface and a plane, and a pore channel structure arranged in the closed body, and the pore channel structure is a completely-through or partially-through porous network. The chemical composition of the porous particle body is a single component or a composite component of two or more of biodegradable inorganic salt ceramic and inorganic oxide, so that the porous particle material is effectively ensured to directly fill various bone defects to form a high-filling close accumulation body, and a through porous network is constructed; local displacement of single particles in the accumulation body after operation is avoided, rapid regeneration and repair of bone injury are promoted, complications are autonomously prevented, and clinical application value is achieved in the field of bone defect repair promotion.

Description

Technical Field

[0001] The utility model relates to a biomedical material, in particular to a biodegradable porous granule with high filling property, belonging to the field of bone tissue regeneration and repair. Background Art

[0002] Bone injuries in various parts of the human body caused by various external and self-inflicted impacts (punctures), falls, acute / chronic diseases and their complications, as well as the need for surgical treatment of certain diseases, often require the implantation of repair materials within the bone injury to improve the efficiency of bone healing and repair. Bone injury morphology varies across age groups and locations, and considering the patient's underlying pathological factors, the scale and morphology of the bone injury determine the implant material's need for good filling properties and the prevention and control of certain side effects and complications. These issues are core issues that need to be considered and addressed in the design and manufacture of bone repair materials.

[0003] Most of the bone repair materials in the existing technology are block scaffold materials with a pore structure. The morphology of these materials varies greatly, and they are often out of step with the simultaneous requirements of multiple aspects of performance and function such as material structure, function, morphology, etc. required by clinical applications, which makes it difficult for a large number of innovative results of basic research to be directly transformed and applied clinically. It is particularly worth emphasizing that the porous scaffold materials conventionally designed and manufactured according to different scale specifications are often based on the convenience of measurement and pricing in product trade. Manufacturers mechanically set the scale and appearance of some porous scaffold blocks, which lack the matching with clinical individualized applications. When used in clinical bone defect filling, these porous scaffolds often need to be temporarily trimmed or even crushed, which not only brings additional labor to the surgical implantation process, but also causes treatment risks due to problems such as mismatch and instability in the integration of the porous block and the bone defect cavity. Secondly, conventional biological granular materials are also produced and processed by first cutting and crushing the whole and then cutting and crushing, which will cause a large number of edges and corners in the particles, making the particle size and morphology extremely irregular and uniform (such as the attached Figure 1As shown in the figure, the filling rate of bone defects is low, the filling property is poor, and then there will be a situation where the local part of the bone defect is not fully filled by the particles, resulting in a large cavity, and the mechanical conduction between the particles cannot be stable and balanced for a long time, and the particles are easily displaced, which destroys the new blood vessel network and causes a new inflammatory reaction, causing the new bone tissue to grow slowly or even not grow. Therefore, the design, processing and clinical surgical implantation of these conventional bone repair biomaterials are out of the ideal requirements of clinical application. It is not difficult to understand that similar problems will be faced in the repair of bone trauma in living animals (or pets). On the contrary, the shape of some plant seed particles or the shape of balls used in sports can ensure that their accumulation forms a relatively high filling property and is not prone to sliding movement. At the same time, the particles can enter the bone defect from the small wound to the larger inner space in sequence to efficiently fill it. Therefore, these granular materials constructed with particles with a curved appearance are bound to be beneficial to bone defect filling.

[0004] In other words, the porous particles used for bone repair in the prior art are often in the form of rectangular, cubic or cylindrical porous scaffolds. The fragments of these porous scaffolds after being damaged have different shapes and sharp corners. When the porous scaffolds or the broken fragments are implanted in the bone defect, they will form larger pores with the repair site, which may even lead to additional treatment risks in some cases. Utility Model Content

[0005] The purpose of the utility model is to provide a biodegradable, highly filling porous granule, the outer surface of which is a curved closed body, so that any porous granules can form effective contact and thus achieve relatively tight stacking. When such porous granules come into contact with bone defects, they can reduce excessive pores and gaps, and avoid loosening and displacement of particles due to unstable contact after surgery, destroying the vascular network, and causing new inflammatory reactions.

[0006] This solution provides a highly filling porous granular body, comprising: a closed body with a continuous curved surface or a combination of a curved surface and a flat surface, and a pore structure built into the closed body, wherein the pore structure is a fully or partially through-hole porous network, and the chemical composition of the porous granular body is a single component and / or a composite component of two or more biodegradable inorganic salt bioceramics and inorganic oxides.

[0007] Compared with the existing technology, this technical solution has the following characteristics and beneficial effects: constructing porous particles with a curved appearance that are convenient for implantation and repair of bone defects, the porous particles can be implanted into the bone defect with the help of a smaller incision and achieve high-density filling, while avoiding sharp edges that damage the host tissue at the material-tissue interface, and through the composite or gradient distribution design of multiple active and functional material components, promoting bone regeneration and repair and preventing various complications.

[0008] The beneficial effects of this program are reflected in:

[0009] 1) In terms of microstructure, the highly filled porous particles prepared by 3D printing additive manufacturing technology have a porous interior that is conducive to rapid vascularization, blood supply, and nutrient transport; the micropore density within the macropore wall can also be widely adjusted, and the interconnection of adjacent macropores is very conducive to cell migration.

[0010] 2) In terms of material appearance, an outer wall with continuous curved surfaces is conducive to the relatively dense stacking of any number of particles, reducing the problem of excessive local gaps that slows repair efficiency or even delays healing; secondly, it is also beneficial to implant the material into a larger bone defect after opening up a smaller soft tissue on the body surface. The curved surface design can reduce the chronic inflammatory response of sharp edges to the tissue, reducing the risk of chronic inflammation and infection after surgery.

[0011] 3) In terms of operability, highly filled porous granules produced using photopolymerization 3D printing achieve ideal control over the pore size, porosity, and inner and outer diameters of any localized porous biomaterial. Furthermore, after calcination, the granules can be directly sterilized, reducing the complexity of sterilization within the pores of the highly filled porous biomaterial. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 It is a schematic diagram of the appearance structure of a porous scaffold according to the prior art and the particles after crushing.

[0013] Figure 2 It is the appearance, cross-section and structural parameters of highly filled porous particles in different forms.

[0014] Figure 3 This is a scanning electron microscope image of the surface pore structure of the magnesium-sodium co-doped wollastonite ceramic particles of the present invention.

[0015] Figure 4 The microporous structure of the ellipsoidal curved surface and circular plane portion of the zinc-sodium doped wollastonite ceramic porous particle of the present invention is photographed by a scanning electron microscope.

[0016] Figure 5 This is a schematic diagram of the appearance of 3D-printed strontium-sodium doped porous wollastonite. DETAILED DESCRIPTION

[0017] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field are within the scope of protection of the present invention.

[0018] Those skilled in the art should understand that, in the disclosure of the present invention, the terms "longitudinal", "transverse", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like indicating the orientation or position relationship are based on the orientation or position relationship shown in the accompanying drawings, which are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, the above terms cannot be understood as limiting the present invention.

[0019] It is to be understood that the term "one" should be understood as "at least one" or "one or more", that is, in one embodiment, the number of an element may be one, while in another embodiment, the number of the elements may be multiple, and the term "one" should not be understood as a limitation on the quantity.

[0020] Before explaining the specific content of this solution, we first explain a series of concepts that may be involved in this patent solution:

[0021] Highly filling porous particles:

[0022] For the purposes of this invention, "highly filling porous granules," also referred to as "porous granules," refer to a class of artificially constructed, non-destructive granular materials with a curved surface, used to promote rapid repair of bone defects in various parts of the human body or living animals. The porous granular materials possess ordered macropores on both the surface and interior. The morphology, particle size, and internal macropore and micropore dimensions of the porous granular materials can be optimized through computer 3D modeling and the addition of pore-forming agents. Furthermore, there are no strict restrictions on the morphology and dimensions of the porous granular materials, nor on the interpenetration of the macropores. These porous granular biomaterials can be implanted into a patient's bone defect via surgery or injection, thereby filling the defect area, providing mechanical support, and promoting new bone growth. Furthermore, these materials can be used as carriers to deliver growth factors or cells to the defect, further promoting bone remodeling. High filling capacity refers to the fact that the curved surface treatment of the granular materials allows the granules to stack tightly together, resulting in a high filling capacity within the bone defect.

[0023] Components

[0024] For the purposes of the present invention, "component" refers to bioceramics and bioglass ceramics with incomplete chemical composition, and also includes inorganic salt bioceramics, biocompatible inorganic oxides and / or bioglass ceramics with consistent chemical composition but different degrees of crystallinity; "component" refers to the chemical composition and physical phase of the inorganic substance added to the photosensitive resin before digital optical three-dimensional printing, which can be a completely glassy phase substance or an inorganic chemical substance containing a partial glassy phase, and can contain oxides of a single metal or non-metal, or a complex of two or more metal or non-metal oxides. These chemical substances are transformed into completely crystalline bioceramics or non-completely crystalline glass ceramics containing a glassy phase after high-temperature treatment; the consistency of chemical composition refers to the types or relative content levels of all metal ions, acid ions or oxides, and the relative content level of the chemical composition refers to a difference of more than 0.01% in their molar percentage.

[0025] Biodegradation

[0026] For the purpose of the present invention, "biodegradation" means that inorganic non-metallic biomaterials with excellent biosafety and biocompatibility can be dissolved in tissue fluid or degraded and absorbed by the metabolic process of cells in the human body. There is no strict limit on the biodegradation rate of each component in the material, and the time span for complete degradation can be three months to two years. The composition of all inorganic ions and acid ions released during the degradation process can regulate / promote vascularization efficiency and bone regeneration efficiency, inhibit inflammatory reactions or inhibit and kill bacteria, and even mediate soft tissue repair at the interface with bone.

[0027] doping

[0028] For the purpose of the present invention, "doping" refers to an inorganic substance formed by partial replacement of specific metal ions and acid ions in inorganic salt bioceramics and bioglass ceramics by one or more other metal ions and acid ions, and does not have a physically separated second independent phase; the doped heterogeneous ions and / or acid ions can be compounds containing doped heterogeneous ions and / or acid ions actively added to the reaction system of the synthetic bioceramic or bioglass ceramic powder, or the heterogeneous ions and / or acid ions brought by the chemical raw materials required for the synthetic powder are not actively and completely removed and remain in the synthetic powder.

[0029] 3D printing

[0030] For the purposes of the present invention, "three-dimensional printing" refers to the use of computer three-dimensional modeling software to design a porous granular biomaterial model with an external shape and internal porous structure that match specific requirements. Then, a mixture slurry of inorganic biomaterial powder, pore-forming agent particles and photosensitive resin is selectively photocured and layered according to the three-dimensional model of the porous granular biomaterial. The slurry that has not been photocured can be removed by water washing to form a print whose external shape and internal structure match the three-dimensional porous granular biomaterial.

[0031] Redundant design

[0032] For the purpose of the present invention, "redundant design" refers to the use of computer three-dimensional modeling software to predict the degree of shrinkage during the sintering process of porous granular biomaterials and perform proportional adjustment of the three-dimensional model, which can avoid deviations between the appearance, size, and internal pore dimensions of the porous granular biomaterials after sintering and the specific requirements of the bone injury site.

[0033] Non-completely through micropores

[0034] For the purpose of the present invention, "non-completely through pores" are a collection of isolated, completely closed pores with a pore size of less than 20 microns, and there is no strict limit on the proportion of through pores.

[0035] Three-periodic minimizing surface

[0036] For the purpose of this invention, "triply periodic minimal surfaces" refers to holes with completely curved surfaces at any local position on the hole surface, and are usually holes with triply periodic minimal surfaces (TPMS) structural characteristics, including but not limited to Gyroid, IWP, Diamond, and FRD structures.

[0037] Basically does not contain

[0038] For the purposes of the present invention, "substantially free" means that the molar percentage of specific inorganic ions and acid ions in inorganic matter in bioceramics and bioglass ceramics is less than 0.05%, more preferably less than 0.02%, and more preferably less than 0.01%, and most preferably 0.0 to 0.01 mol%, including all ranges contained therein.

[0039] other

[0040] Except in the examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or reaction conditions, physical properties of materials and / or use may optionally be understood as modified by the term "about."

[0041] Unless otherwise stated, all amounts are based on the mass of the final porous particulate biomaterial.

[0042] It should be noted that within any range of stated values, any particular upper value can be associated with any particular lower value.

[0043] For the avoidance of doubt, the term "comprising" is used to mean "including" but not necessarily "consisting of" or "composed of...." In other words, the listed steps or options do not have to be exhaustive.

[0044] The disclosure of the invention found herein should be considered to cover all embodiments found in the claims as they are interdependent, regardless of the fact that the claims are not multiply dependent or redundant.

[0045] For the present utility model patent, when using degradable porous granules for various bone injury indications, they can be designed and manufactured according to the requirements of defect size and bone reconstruction efficiency at the site, the pore size, appearance size and multifunctionality. For example, in craniomaxillofacial surgery applications, the particle size can be less than 1.5 mm, and in larger bone defects of limb bones, the particle size can be at the level of 1 to 8 mm. At the same time, when filling and repairing various bone trauma defects, porous granular materials of different particle sizes can be mixed and implanted in a certain proportion to further improve the filling capacity, and these granular materials of different sizes can also be obtained by simultaneous printing on the same printing device using different models. The optimal porous granular material design is that the particle surface is mainly composed of a continuous curved surface or a continuous curved surface surrounded by one or two flat surfaces, which is convenient for manufacturing and implantation and achieves high filling capacity. Therefore, the chemical composition, component distribution, and pore structure design strategy of the porous granular biomaterial described in the present utility model will comprehensively solve the functional requirements of material activity, degradation rate, and coordinated prevention and control of inflammation and infection involved in various clinical bone injury indications.

[0046] The technical solution adopted in this scheme is to provide a highly filling porous granular body, which is a closed body with a continuous curved surface or a combination of a curved surface and a flat surface, and a pore structure built into the closed body. The pore structure is a completely through-hole or partially through-hole porous network. The chemical composition of the porous granular body is a single component and / or two or more composite components of inorganic salt bioceramics and inorganic oxides, whether doped with biodegradable heterogeneous ions or not; preferably, the maximum size of the particles of the porous granular body does not exceed 8 mm.

[0047] Preferably, the outer wall surface of the porous granules is a closed surface composed of a complete continuous curved surface. In this case, the porous granules are in the form of a complete ellipsoid or sphere.

[0048] Preferably, the outer wall surface of the porous granule is a closed surface composed of a partial continuous curved surface and at least one flat surface. In this case, the porous granule can be in the form of a partial ellipsoid, a circular cake or a sphere.

[0049] Preferably, the porous particles are in the form of an ellipsoid, the major axis diameter and the minor axis diameter of the ellipsoid model are 6.8 microns and 3.8 microns respectively, and the porosity of the ellipsoid model is 62%.

[0050] Preferably, the porous particles retain the appearance of a combination of curved and flat surfaces of an ellipsoidal 4 / 5 structure, and the lengths of the major axis and minor axis of the ellipsoidal model are 5.1 microns and 3.8 microns, respectively.

[0051] Preferably, the porous particles retain the appearance of a combination of curved and flat surfaces of an ellipsoidal 1 / 2 structure, and the major axis diameter and minor axis diameter lengths of the ellipsoidal model are 3.6 microns and 2.8 microns, respectively.

[0052] Preferably, the porous particles retain the appearance of a combination of a curved surface and two planes of an ellipsoidal 3 / 5 structure, with a maximum transverse diameter and height of 1.88 μm and 1.71 μm respectively, and the diameters of the upper and lower circular planes are both 1.47 mm.

[0053] Preferably, the arc center of the continuous curved surface of the outer wall surface is located inside the porous particle body.

[0054] Preferably, the pore walls of the pore structure of the highly filling porous granules are curved surfaces, and the curved surface shapes include but are not limited to spherical surfaces, spherical surfaces, ellipsoidal surfaces, cylindrical side wall surfaces, honeycomb hole side wall surfaces, three-period minimizing curved surface surfaces, or any combination of several of them.

[0055] The curved surface morphology of the pore wall is similar to the pore wall surface of cancellous bone and the pore structure composed of a three-periodic minimization surface of a porous network.

[0056] The curved surface in the porous particle body can be any pore composed of a three-periodic minimizing surface similar to the pore network of cancellous bone, and the curved surface can be any pore composed of a three-periodic minimizing surface similar to the pore network of cancellous bone, including but not limited to Gyroid, IWP, Diamond, and FRD structures.

[0057] Preferably, the pore structure of the highly filling porous granules is composed of macropores and micropores. The pore size and microstructure of the highly filling porous granules are not strictly limited. They can be larger pores of any shape designed using computer modeling. The larger pores in the calcined granular biomaterial can be 150 to 800 microns in size. They can also be micropores with a pore size of less than 20 microns remaining after adding a pore-forming agent to the printing slurry and volatilizing it through high heat treatment. There are no strict restrictions on the combination of pores of different scale levels in the porous granular biomaterial, and there is no strict limit on the porosity in any gradient pore range.

[0058] The porous granular biomaterial contains micropores, which are pores no larger than 20 microns.

[0059] The porosity of the porous granules is 25% to 78%. The pores of the porous granules are composed of macropores with a scale of 150 to 800 microns and micropores less than 20 microns. There is no strict limit on the scale of the through holes between the macropores, and the preferred scale is 250 to 650 microns.

[0060] The porous particles can be obtained by 3D printing and sintering of biodegradable inorganic salt ceramics and / or inorganic oxides. The chemical composition of the porous particles is composed of a single component or a composite of two or more components. The composite components are distributed in a two-phase mixture or in a gradient distribution formed along a specific direction of the particles.

[0061] The distribution of components in the highly filling porous granules can be a gradient component distribution structure formed by sequential, alternating, or random superposition along any direction. Correspondingly, the pore structure of the highly filling porous granules can be a gradient distribution structure formed by sequential, alternating, or random superposition of pores of different pore sizes or pore morphologies.

[0062] The highly filling porous granules are composed of an inorganic salt compound, an oxide, and a glassy oxide composite. The glassy oxide composite includes a glassy substance composed of at least two inorganic oxides. The molar percentages of the various phase components are:

[0063] Biodegradable inorganic salt bioceramics 5%-99.99%

[0064] Oxide 0.05%-30%

[0065] Glassy oxide complex 0.01%-95%.

[0066] The powder of the biodegradable inorganic salt bioceramic can be any one of wollastonite, pseudowollastonite, dicalcium silicate, tricalcium silicate, magnesia chrysocolla, white wellstone, magnesia wellstone, disilicate calcium phosphate, blue silicate, α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, strontium metasilicate, dicalcium silicate, tristrontium silicate, or a mixture of any at least two inorganic salt bioceramics, and there is no particular limitation on the doped heterogeneous ions in the inorganic salt bioceramic.

[0067] The biodegradable inorganic salt bioceramic powder does not have strict requirements on the type and content level of doped heterogeneous ions. Any inorganic ions or inorganic acid ions that are beneficial to improving anti-infection, reducing inflammation, promoting vascularization or bone regeneration and repair efficiency can be doped into the bioceramic or bioglass ceramic powder.

[0068] The bioceramic powder can be a completely or partially crystalline substance of silicates, phosphates, borates, and sulfates of calcium, magnesium, zinc, and strontium that are safe for human body and biodegradable, or a completely or partially crystalline substance of a metal complex salt of silicates, phosphates, borates, and sulfates of calcium-magnesium, calcium-zinc, calcium-strontium, magnesium-strontium, zinc-strontium, magnesium-zinc, sodium-calcium, sodium-magnesium, sodium-zinc, potassium-calcium, potassium-magnesium, and potassium-zinc, or a silicon-phosphate or silicon-borate of calcium, magnesium, and zinc.

[0069] The crystalline material of the powder of the biodegradable inorganic salt bioceramic is preferably one of β-wollastonite, α-wollastonite, white wellstone, schoenite, magnesia feldspar, anhydrous calcium phosphate, β-tricalcium phosphate, α-tricalcium phosphate, amorphous calcium phosphate, dicalcium silicate, magnesium silicate, magnesium phosphate, distrontium silicate, tristrontium silicate, calcium disilicate phosphate, and blue silicon apatite, or any combination thereof.

[0070] Preferably, the biodegradable inorganic salt bioceramic is any one of heterogeneous ion-doped β-wollastonite, α-wollastonite, magnesia chrysocolla, leucoglossite, magnesia chrysocolla, strontium metasilicate, distrontium silicate, tristrontium silicate, or a mixture of at least two inorganic salt bioceramics.

[0071] Example 1: [Magnesium-sodium co-doped wollastonite ceramic porous granular material]

[0072] A co-doped wollastonite ceramic powder containing 0.62% sodium ions and 8.7 mol% magnesium ions replacing some calcium ions is mixed and stirred with a photocurable resin at a mass ratio of 100:60 to form a slurry capable of photocurable three-dimensional printing. The slurry is then added to the printing tank of a photocurable printer. An ellipsoidal porous structure model (the pore morphology is an IWP structure, the major axis diameter and minor axis diameter lengths of the ellipsoidal model are 6.8 mm and 3.8 mm, respectively, and the porosity of the ellipsoidal model is 62%) that is simultaneously enlarged by 22% according to a redundant design is densely arranged. The number of models on the synchronous printing format reaches 40. The printing device is turned on to perform three-dimensional printing according to the ellipsoidal model until the model printing is completed. The printed material is then rinsed with water to remove uncured resin slurry, and the porous composite is dried and set aside.

[0073] 2) The porous printed particles in step 1) were heated from room temperature to 480°C at a rate of 1°C / min and kept at that temperature for 30 minutes for degreasing, and then continued to be heated to 1120°C at a rate of 3°C / min and sintered for 2 hours. After the insulation was completed, the particles were naturally cooled with the furnace temperature to obtain magnesium-sodium co-doped wollastonite ellipsoidal porous particles.

[0074] After testing, the scale ratio of the sintered magnesium-sodium co-doped wollastonite ellipsoidal porous particles was less than 6% of the three-dimensional model before magnification. Flame plasma emission spectroscopy (ICP) analysis showed that the substitution rate of magnesium for calcium was 8.6 mol%, and the mass percentage of sodium in the bioceramic particles was 0.67%.

[0075] MicroCT three-dimensional reconstruction showed that the ellipsoidal porous particles were as follows. Figure 2 As shown in A, the outer diameters along the long and short axes have no significant changes compared with the model, and the macropores remain continuous. The maximum pore size of the IWP is 570 μm, and the average pore size is 552 μm.

[0076] The outer surface layer of the ellipsoidal porous particles (such as the attached Figure 4 The IWP structural pores can be seen in the figure, which is consistent with the pore shape of the model design.

[0077] Example 2: [Two porous granular materials of wollastonite ceramics doped with zinc-sodium and strontium-sodium, respectively]

[0078] 1) Two wollastonite ceramic powders, each containing 0.42% sodium ions and 4.8% zinc ions and 5.9% strontium ions replacing some calcium ions, were mixed with a photosensitive resin at a mass ratio of 100:55. Polyacrylic acid microspheres with a diameter of 8-10 μm were then added to the powders at a mass ratio of 100:10 and 100:8, respectively, and stirred to form two printable slurries. First, the zinc-sodium co-doped wollastonite ceramic powder slurry was added to a printing pool. A 3D biomaterial model of the particulate material was enlarged by 20% according to a redundant design (retaining the ellipsoidal 4 / 5 structure with a combined curved and flat surface, an IWP structure, and a pore structure with a major and minor axis length of 5.1 mm and 3.8 mm, respectively, and a porosity of 56%). Thirty-six models were printed simultaneously. The photocurable printer was then activated to perform layer-by-layer photocurable printing until all 3D models were printed. The printed material was then rinsed with tap water to remove any uncured resin slurry. Similarly, another strontium-sodium co-doped wollastonite ceramic powder slurry was added to the printing tank and printed according to the redundant design. A 20% magnified three-dimensional model of the granular biomaterial (retaining the appearance of the combined curved and flat surfaces of the 3 / 5 ellipsoid structure, with the pores presenting an IWP structure; the major and minor axis lengths of the ellipsoid model were 4.6mm and 3.8mm, respectively, and the porosity was 60%). The printed particles were also rinsed. Then, the two printed particles were dried at 60°C and set aside.

[0079] 2) The two types of zinc-sodium and strontium-sodium obtained in step 1) are respectively doped with ceramic powder printing particles, and the heating rate from room temperature to 450°C is 1°C, and they are kept at 480°C for 45 minutes for degreasing. Then the heating rate is increased to 1150°C at a rate of 2°C per minute and calcined for 3 hours. After the insulation is completed, they are naturally cooled with the furnace temperature to obtain porous granular biomaterials of zinc- and strontium-doped wollastonite ceramics, respectively.

[0080] After testing, the two types of non-complete ellipsoidal porous particles of wollastonite that retained the ellipsoidal 4 / 5 structure and 3 / 5 structure, respectively, were co-doped with zinc-sodium and strontium-sodium after sintering. The scale shrank by no more than 4.6% compared with the three-dimensional model. ICP analysis showed that the substitution rate of zinc for calcium was still 4.8 mol%, and the substitution rate of strontium for calcium was still 5.6 mol%.

[0081] The microCT three-dimensional reconstruction showed that the sintered zinc-sodium and strontium-sodium co-doped wollastonite porous granular biomaterials were as shown in the attached figure. Figure 2 B and Figure 2 As shown in C, the outer diameter along the long axis and the short axis has no significant change compared with the model, and the large hole channel maintains continuity.

[0082] The SEM observation of zinc-sodium co-doped wollastonite ceramic porous granular materials (such as the attached Figure 5The ellipsoidal surface and circular plane part (as shown in the figure) both present an IWP-type pore structure, which is consistent with the pore shape of the model design.

[0083] Example 3: [Axially Gradient Magnesium-Strontium-Zinc-Sodium Co-doped Wollastonite Ceramic Porous Granular Material]

[0084] 1) Three kinds of wollastonite ceramic ultrafine powders, each containing 0.56% sodium ions and 7.8% magnesium ions, 5.6% strontium ions, and 3.9% zinc ions, are co-doped with calcium ions, respectively, and are mixed and stirred evenly with polymethyl methacrylate with a particle size of 5 μm and a photocurable resin at a mass ratio of 100:10:65 to form three kinds of printing slurries. First, the magnesium-sodium co-doped wollastonite ceramic slurry is added to the material tank of the photocurable printer. According to the redundant design, a semi-ellipsoidal three-dimensional structure model (using an IWP type structural channel, the channel is an IWP structure; the major axis diameter and the short axis diameter of the ellipsoidal model are 18%) are simultaneously enlarged. The axial diameter lengths are 3.6 mm and 2.8 mm, respectively, and the porosity is 60%), and the number of models on the synchronous printing format reaches 42. The light-curing printing device is then started to perform three-dimensional printing in the direction of the long axis of the semi-ellipsoidal model. When the porous granular biomaterial is printed to one-third and two-thirds of the length, the residual slurry is respectively aspirated, and strontium-sodium co-doped and zinc-sodium co-doped wollastonite ceramic slurries are added in sequence and printing is continued until the model printing is completed. The printed particles are then rinsed with tap water to discharge the uncured resin slurry in the porous gaps. The porous composite is then dried at 60°C for standby use.

[0085] 2) The porous printed particles obtained in step 1) were heated from room temperature to 460°C at a rate of 1°C, and kept at 460°C for 60 minutes for degreasing, and then the temperature was raised to 460°C at a rate of 2°C per minute. 11 The material was calcined at 50°C for 20 minutes, then rapidly cooled to 1080°C after 10 minutes and sintered for 2 hours. After the heat preservation was completed, the material was naturally cooled with the furnace temperature to obtain a wollastonite porous granular biomaterial with different magnesium-strontium-zinc-sodium gradient distributions.

[0086] After testing, the replacement rate of calcium by magnesium, strontium and zinc in the sintered semi-ellipsoidal porous particles decreased by 52%, 69% and 78% respectively compared with the powder, and the content of sodium ions remained stable, indicating that the curved particles shrank, causing the content of non-stoichiometric wollastonite components in the post-printing part to decrease. The appearance of the Mg, Sr and Zn ion gradient co-doped wollastonite high-filling porous granular biomaterial is shown in the attached figure. Figure 2 As shown in D, the particle still has a semi-ellipsoidal appearance, and the internal large pores have excellent penetration. Because the redundant design is not enlarged enough to offset the shrinkage caused by sintering, the major axis diameter and minor axis diameter of the particle after sintering are longer than those of the model.

[0087] Example 4: [Sodium-doped β-tricalcium phosphate ceramic porous granular material]

[0088] 1) Similar to step 1) in Example 1, except that β-tricalcium phosphate ceramic powder doped with 8.8% sodium ions partially replaced the calcium ions with magnesium ions and wollastonite ceramic powder containing 0.62% sodium ions. The printed model was obtained by cutting off 1 / 5 of the upper and lower portions of the complete ellipsoid, leaving the middle 1 / 5. The other steps were the same as step 1) in Example 1. The ceramic slurry was then printed, and the granules were washed and dried to obtain a granular material for later use.

[0089] 2) The sodium-doped β-tricalcium phosphate printed particles obtained in the above step 1) are heated from room temperature to 450°C at a rate of 1°C, and are kept at 480°C for 45 minutes for degreasing. The temperature is then increased at a rate of 2°C per minute to 1160°C and calcined for 3 hours. After the insulation is completed, the particles are naturally cooled with the furnace temperature to obtain porous granular biomaterials of sodium-doped β-tricalcium phosphate ceramics.

[0090] After testing, the non-complete ellipsoidal porous particles of the sintered sodium-doped β-tricalcium phosphate that retain the structure of the middle 3 / 5 of the ellipsoid have a scale that is no smaller than 6.9% of the three-dimensional model. ICP analysis shows that the mass percentage of sodium ions in the β-tricalcium phosphate ceramic particles is 8.8%.

[0091] The microCT three-dimensional reconstruction showed that the sintered zinc-sodium and strontium-sodium co-doped wollastonite porous granular biomaterials were as shown in the attached figure. Figure 2 As shown in Figure E, the outer diameters along the major and minor axes do not change significantly compared with the model, and the macropores remain continuous.

[0092] The present invention is not limited to the above-mentioned optimal implementation mode. Anyone can derive other forms of products under the inspiration of the present invention. However, no matter what changes are made in the shape or structure, any technical solution that is the same or similar to that of the present application falls within the scope of protection of the present invention.

Claims

1. A porous granular body with high filling capacity, characterized in that: include: A closed body with a continuous curved surface or a combination of a curved surface and a flat surface, and a pore structure built into the closed body, wherein the pore structure is a fully or partially through-hole porous network, and the porous granular body is obtained by 3D printing and sintering of biodegradable inorganic salt ceramics.

2. The highly filling porous granular body according to claim 1, characterized in that: The porous granules are in the form of a whole or part of an ellipsoid, a round cake or a sphere.

3. The highly filling porous granular body according to claim 1, characterized in that: The arc center of the continuous curved surface of the outer wall surface is located inside the porous particle body.

4. The highly filling porous granular body according to claim 1, characterized in that: The pore wall of the pore structure is a curved surface, and the curved surface morphology is similar to the pore wall surface of cancellous bone and the pore structure composed of a three-periodic minimization surface of a porous network.

5. The highly filling porous granular body according to claim 4, characterized in that: The curved surface shape includes but is not limited to a spherical curved surface, an ellipsoidal curved surface, a cylindrical side wall curved surface, a honeycomb hole side wall curved surface, a three-periodic minimizing curved surface, or any combination thereof.

6. The highly filling porous granular body according to claim 1, characterized in that: The pore structure is composed of macropores and micropores.

7. The highly filling porous granular body according to claim 6, characterized in that: The size of the macropores is 150 to 800 micrometers, and the size of the micropores is no more than 20 micrometers.

8. The highly filling porous granular body according to claim 1, characterized in that: The maximum dimension of the particles of the porous granular body does not exceed 8 mm.

9. The highly filling porous granular body according to claim 1, characterized in that: The porosity is 25% to 78%.

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