CN117815455A - Multifunctional hollow porous screw and preparation method thereof - Google Patents

Abstract

The invention provides a multifunctional hollow porous screw and a preparation method thereof, wherein a zinc ion and magnesium ion gradient distribution mode is adopted to realize the whole-course prevention and control of bacterial breeding of a bioactive ceramic screw, overcome the infection risk induced by the holding nail cap part of the screw, effectively reduce inflammatory reaction in injury and accelerate osseointegration, and simultaneously can adjust the sintering property, biodegradability and fracture-resistant mechanical property of the bioactive ceramic; meanwhile, the side wall of the threaded body of the multifunctional hollow porous screw is provided with a windowing, a through micropore and an internal connection supporting beam, so that early osseointegration and long-term anti-pulling capacity are improved, and the clinical application scope is enlarged; the preparation method comprises the steps of guiding the biological ceramic powder slurry containing functional ions into a printing groove in stages according to a three-dimensional model of the screw, performing photo-curing printing, and then flushing, drying and sintering.

Description

A multifunctional hollow porous screw and preparation method thereof

Technical Field

The invention relates to medical biomaterials in the field of bone regeneration, repair and reconstruction, and in particular to a multifunctional hollow porous screw and a preparation method thereof.

Background technique

For common fractures, bone loss bone trauma, and soft tissue tearing from bones and requiring repair in orthopedics, dentistry, maxillofacial surgery, plastic surgery, etc., clinicians usually need to use internal fixation devices to fix the broken ends after anastomosis, or fix the implants to prevent displacement, or use sutures to repair the separated soft tissues. Regardless of which method is used, internal screws are required to fix other instruments, or fix bone blocks or artificial materials, and anchor the sutures to the bones through screws. Currently, the screws used in clinical practice include non-degradable metals, alloys or polymer materials, such as titanium nails, titanium alloy nails, metal tantalum nails and polyetheretherketone (PEEK) nails (Chinese patent, CN106137288A); there are also screws constructed using degradable polymer materials, inorganic ceramic materials, degradable metals or alloy materials, such as polylactic acid nails, citric acid nails, calcium phosphate ceramic nails, magnesium alloy nails, etc. (Chinese patent, CN106137288A). The application of screws made of these materials in orthopedics, dentistry, etc. is mainly to utilize their good mechanical properties to exert their fixation function, or to relieve lesions by applying drugs on the surface, but the screws themselves lack positive biological effects on the healing and repair of the damaged parts, especially the screws also lack autonomous anti-inflammatory and anti-infection functions. Once the degradation products of the screw materials themselves induce inflammatory reactions, or carry bacteria into the damaged parts, it may not only cause potential postoperative infection risks, but also cause the early internal fixation needs to be seriously affected. Secondly, there are also some technical solutions that use conventional technical processes to design the screw microstructure or component structure, such as Chinese invention patents CN104997540A, CN106137288A, CN108403175A, CN113693654A, and CN105877798A, but the pull-out resistance and processing costs involved in their processing technology are issues that cannot be ignored.

Generally, simply developing biodegradable screws with high initial mechanical strength cannot meet clinical needs. The screws must also be able to control inflammation, prevent infection, and be used in a variety of clinical scenarios, and even bring better added value to the treatment than expected. For example, microstructure optimization ensures early bone integration and improves internal fixation strength. The degradation products of bone screws can remodel adjacent osteoporosis, increase bone density, and reduce fracture risks. These biological effects will be a major advancement in the clinical treatment of bone tissue and adjacent soft tissue injuries.

A detailed analysis shows that the screws used in various clinical applications such as orthopedics, stomatology, and maxillofacial surgery need to meet the two core requirements of efficient bone integration and long-term internal fixation. At the same time, the screws can also store and transport some functional substances, or use the functional ions and molecules contained in themselves to collaboratively solve the problem of damage repair, and the material itself can be degraded with the tissue repair process. However, conventional screw designs often lack the coordination of integrated design for clinical application indications and integrated design for biological multifunctionality, so that the physical properties, physicochemical properties, biological functions, and structural designs of raw materials are not organically integrated, which is not conducive to large-scale manufacturing cost control and multiple performance optimization. The designs of screws (including anchors) of conventional calcium phosphate, calcium silicate, and calcium magnesium silicate ceramics at present lack the optimization of their sintering properties, comprehensive mechanical properties, and multiple biological functions, such as the scheme mentioned in Chinese patent CN110916735A, and the simple chemical composition and internal structure design still lack the comprehensive consideration and synergistic optimization of the new tissue ingrowth channel network, material-tissue integration efficiency, and post-implantation side effects, and cannot meet the needs of clinical diversity application scenarios.

Specifically, the medical orthopedic screws to date still have the following main problems:

(1) The intrinsic physical properties of the (raw) materials used make them non-degradable or extremely difficult to regulate degradation;

(2) The intrinsic physical properties of the (raw) materials used make the material processing or post-processing methods too cumbersome, the process is complex and the microstructure accuracy is poor;

(3) The mechanical properties of the (original) materials used are poor, making the screws brittle or easy to break after being formed, or swelling and shrinking rapidly after being implanted in the body, making it difficult to maintain a stable shape;

(4) The screws lack sufficient biological functionality, so the management of the implant site wound requires the use of clinical experience and drugs to prevent and control the risk of postoperative complications;

(5) Early bone integration efficiency, long-term internal fixation and anti-pullout ability often only rely on the screw material and thread locking. Once the screw material has poor bone integration ability and the degradation rate is uncontrollable or unreliable, it is easy to cause risks such as early loosening or even long-term instability;

(6) The lack of a universal structural design for various indications requires that internal fixation and anchoring screws must be manufactured separately.

Therefore, it is necessary to break through the existing design concept of medical screws and develop screws with extremely outstanding multifunctional characteristics that meet the needs of a new generation of multiple indications. While providing multiple biological functionalities, the pull-out resistance does not only rely on the structural design of the thread, but can also make full use of the biological activity of the material to promote the rapid growth of new tissue into the screw and significantly improve the pull-out resistance and other properties. Only in this way can we comprehensively solve the wide range of indication needs in the clinical fields of orthopedics, dentistry, plastic surgery, etc. and avoid many postoperative risks.

Summary of the invention

The purpose of the present invention is to provide a multifunctional hollow porous screw and a preparation method, which can solve the many defects of conventional medical screws in raw material properties, mechanical properties, microstructural characteristics, and preparation methods in a package, and can integrate and expand the various biological function requirements of screws. The main innovative idea of the present invention is to use the unique inflammation control function and anti-bacterial infection function of functional magnesium and zinc ions, and use the content levels of the two in different parts of the screw to achieve multiple biological functions synergistic and synchronous optimization, and further regulate the sintering performance, biodegradability and fracture resistance of bioactive ceramics through these functional ions. The gradient distribution of functional ions and the through micropore design on the side wall of the thread body can overcome the infection risk that the gripping nail cap part in contact with the soft tissue outside the bone is most likely to induce, and strengthen the efficient and firm integration ability of the thread body and bone tissue, significantly improve the anti-pullout ability, and effectively enhance the function of the entire screw.

Before describing the specific content of the present invention, the following noun concepts may be involved in the patent scheme of the present invention:

Multifunctional hollow porous screw:

For the purpose of the present invention, "multifunctional hollow porous screw" refers to a fully biodegradable porous inorganic non-metallic hollow screw used to promote tissue regeneration, repair, reconstruction, internal fixation of bone injuries, bone defects and joint injuries in various parts of the human body, or to facilitate soft tissue healing and repair. It can be used to achieve multiple functions such as fixation, anchoring, sustained release transportation, anti-infection, and control of inflammatory reactions. The microstructure and macroscopic morphology of the screw can be manufactured through computer three-dimensional modeling and three-dimensional printing rapid and compact manufacturing technology. There are no strict restrictions on the appearance and size of the screw.

Gradient distribution:

For the purpose of the present invention, "gradient distribution" means that the content of at least two inorganic magnesium ions and zinc ions in the screw material gradually increases or decreases along the direction from the screw holding nail cap to the thread body and the nail head, ensuring that different parts produce biological functions with specific requirements, that is: if there is a higher content of magnesium ions in the nail head and the thread body, a higher dose of magnesium ions will be released to the part that is in closest contact with the host tissue to effectively prevent and control postoperative inflammatory side effects; conversely, if there is a higher content of zinc ions in the nail holding cap, a higher dose of zinc ions will be released to the part that is more easily exposed to soft tissue or the outside world to prevent a greater risk of infection in this part.

Calcium silicate:

For the purposes of the present invention, "calcium silicate" means a fully crystalline or partially crystalline compound or complex of a stoichiometric or non-stoichiometrically synthesized inorganic non-metallic inorganic salt containing calcium ions, silicate and at least magnesium ions or zinc ions. As shown in the following table, there are differences in the molar percentages of magnesium and zinc in the stoichiometric silicates containing magnesium and zinc, calculated as their oxides.

In the present invention, the molar percentage of magnesium and zinc in the calcium silicate expressed as oxides thereof is 0%-22%. Therefore, the meaning of calcium silicate containing magnesium ions and zinc functional ions refers to wollastonite doped with magnesium ions or zinc ions, or magnesia feldspar [Ca ₂ MgSi ₂ O ₇ , which can be expressed as (CaO) ₂ MgO(SiO ₂ ) ₂ ] or zincite [Ca ₂ ZnSi ₂ O ₇ , which can be expressed as (CaO) ₂ ZnO(SiO ₂ ) ₂ ] containing excessive magnesium ions and zinc ions; when the molar percentage of MgO and ZnO is 22%, it means that part of CaO is replaced by MgO or ZnO during the synthesis of magnesia feldspar and zincite, forming non-stoichiometric magnesia feldspar or zincite (also known as magnesium-rich magnesia feldspar and zinc-rich zincite) with more than 20% excess MgO or ZnO; when the content of MgO or ZnO in the calcium silicate is relatively low, it means wollastonite or pseudowollastonite (chemical formula is CaSiO ₃ , expressed as oxides CaO·SiO ₂ ), part of the calcium ions are replaced by magnesium ions or zinc ions, forming magnesium ion or zinc ion doping (chemical formula is Ca _1-x Mg _x SiO ₃ , Ca _1-x Zn _x SiO ₃ , wherein when x≤0.08, it means that the molar percentage of MgO and ZnO in all oxides does not exceed 6%). It should be emphasized that diopside and magnesia olivine synthesized according to the stoichiometric molar percentage of MgO are not only difficult to sinter and the sintered products are brittle, but also because they are extremely biostable, the biodegradation rate of the two in vivo is extremely slow. The anti-inflammatory biological potential of these two ceramics themselves is extremely limited and is not within the scope of the raw materials described in the present invention. Therefore, the calcium silicates with different functional ion magnesium contents described in the present invention include one or a combination of several of wollastonite, magnesium-doped wollastonite, white wellstone, magnesium-rich white wellstone, magnesium wellstone, magnesium-rich magnesium wellstone, magnesia chalcedony, magnesium-rich magnesia chalcedony, etc., and the calcium silicates with different functional ion zinc contents described in the present invention include one or a combination of several of wollastonite, zinc-doped wollastonite, sintered wellstone, and zinc-rich sintered wellstone.

Components

For the purpose of the present invention, "component" refers to bioceramics and bioglass-ceramics with incomplete chemical compositions. The consistency of chemical composition refers to the type or relative content level of metal ions, acid ions or oxides. The relative content level of chemical composition refers to a difference of more than 0.01% in its molar percentage.

Biodegradable

For the purpose of the present invention, "biodegradation" means that inorganic non-metallic biomaterials with excellent biosafety and biocompatibility can be dissolved by tissue fluid or degraded by cell metabolism in the human body. There is no strict limit on the degradation rate of each component in the material, and the time span for complete degradation can be within three months to two years. The inorganic ion and acid radical ion composition released during the degradation process can regulate/promote the vascularization efficiency and bone regeneration efficiency of various parts, and can also inhibit inflammatory reactions or inhibit and kill bacteria, and can even mediate the healing and repair of soft tissues at the contact interface with bones.

3D Printing

For the purpose of the present invention, "three-dimensional printing" means using computer three-dimensional modeling software to design a screw model whose appearance and internal microstructure match specific needs, and then photocuring a mixture slurry of inorganic non-metallic biomaterial powder and photosensitive resin according to the three-dimensional model of the screw and stacking it layer by layer. The slurry of the unphotocured part can be removed by washing with water to form a printout whose appearance and internal structure match the three-dimensional porous screw.

Redundant design

For the purpose of the present invention, "redundant design" refers to the use of computer three-dimensional modeling software to predict the shrinkage degree of the biomaterial sintering process and perform proportional adjustment of the three-dimensional model, which can avoid deviations between the appearance, appearance size, and internal channel dimensions of the screws obtained after sintering and application requirements.

Through micropores

For the purpose of the present invention, "through micropores" refer to the discretely distributed tiny holes on the side walls of the threaded body that are connected to the internal hollow cavity. The pore size of the micropores is 300-800 microns. Tissue fluid and osteoblast-related cells can efficiently migrate and grow into the hollow cavity from the thread groove surface, which is conducive to the efficient and firm integration of the screw and the host tissue.

Basically does not contain

For the purposes of the present invention, "substantially free" means that the mole percentage of a particular component in the oxide composition of the bioglass in the composition is less than 0.1%, preferably 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 mole %, including all ranges contained therein.

Doping

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 bioceramics and glass-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 (such as magnesium, zinc, etc.) and/or acid ions (such as phosphate and borate) actively added to the reaction system of synthetic ceramic or glass-ceramic powder, or heterogeneous ions (such as sodium, potassium, etc.) and/or acid ions (such as phosphate and borate) brought by the chemical raw materials required for the synthetic powder are not actively and completely removed and retained in the synthetic powder.

other

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".

It should be noted that within any range of specified values, any particular upper value may be related to any particular lower value. 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.

Unless otherwise stated, all quantities are based on the mass of the final multifunctional hollow porous screw.

In a first aspect, the present invention provides a multifunctional hollow porous screw, which is a three-dimensionally printed inorganic non-metallic porous screw having a biodegradable bioactive ceramic or a bioactive glass-ceramic as a matrix and a gradient distribution of functional ions along a specific direction of the screw.

Specifically, the multifunctional hollow porous screw includes: a screw body made of calcium silicate ceramics, the screw body includes a gripping nail cap, a threaded body and a nail head arranged in sequence, and the magnesium ions and zinc ions in the calcium silicate ceramics are distributed in a gradient along the axial direction of the screw body.

The content of at least two inorganic magnesium ions and zinc ions in the multifunctional hollow porous screw of the present invention gradually increases or decreases in the screw material along the direction from the screw cap to the screw head, ensuring that different parts produce biological functions with specific requirements.

In some embodiments, there is a relatively high content of magnesium ions in the nail head and the thread body, and the magnesium ions in these parts of the screw will be released to the area in contact with the host tissue during the degradation process, thereby effectively controlling the degree and duration of postoperative inflammatory response in this area; conversely, there is a high content of zinc ions in the part holding the nail cap, and it releases zinc ions to the part that is more easily exposed to soft tissue or the outside world, thereby preventing a greater risk of infection in this part. In other words, the content of magnesium ions gradually increases along the direction from holding the nail cap to the nail head, and the content of zinc ions gradually decreases along the direction from holding the nail cap to the nail head.

Specifically, the molar percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the nail cap portion, expressed as oxides of magnesium, zinc, calcium and silicon, are not higher than 6% and 23% respectively; the molar percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the nail head portion, expressed as oxides of magnesium, zinc, calcium and silicon, are not higher than 23% and 6% respectively; the molar percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the threaded body portion, expressed as oxides, are between the contents of magnesium and zinc in the nail cap and the nail head portion, respectively.

In this scheme, the multifunctional hollow porous screw can be manufactured by three-dimensional printing technology. Correspondingly, the gradient distribution of different functional ions in the screw can be adjusted by the ceramic components or relative proportions selected when preparing the printing ceramic slurry.

In the second aspect, the present invention provides a multifunctional hollow porous screw, which comprises: a screw body made of calcium silicate ceramics, wherein the screw body comprises a gripping nail cap, a threaded body and a nail head arranged in sequence; wherein the gripping nail cap and the threaded body have a polygonal hollow cavity that is mutually interpenetrating and on the same axis. The advantage of such a setting is that it is convenient for surgical tools to rotate and implant the screw, and avoids the risk of cracking and failure of the slotted part due to stress concentration at the slotted part when the surgical tool rotates the screw to implant the tissue.

The cross-section of the polygonal hollow cavity can be selected as one of a square, a pentagon or a hexagon, and the ratio between the side length of the polygonal hollow cavity and the diameter of the circular surface of the thread groove of the threaded body is 1:(3.0-6.0).

The side wall of the threaded body includes a plurality of through micropores discretely distributed on the thread groove surface, the micropores are completely connected with the hollow cavity in the threaded body, and two adjacent through micropores are arranged along the thread groove surface rotated 450 degrees.

In some embodiments, the size of the through micropores is 300-800 microns; the width of the thread groove surface of the threaded body is 800-1200 microns, and the width of the top surface of the thread protrusion is 10%-90% of the width of the thread groove surface. The angle between the thread groove surface and the side wall of the thread protrusion is 90°-150°; there is no strict restriction on the height of the thread protrusion, and the preferred height of the thread protrusion is 600-1800 microns; the ratio of the diameter of the thread groove circular surface of the threaded body to the maximum outer diameter of the nail cap holding part is 1:(1.2-3.0).

The through micropores may be in the shape of a circle, a square, a hexagonal hole or an ellipse, or any combination thereof. In other words, the through micropores may be micropores of different pore sizes or pore shapes.

A window is provided on the side wall where the threaded body and the nail head are connected, and an internal connecting support beam perpendicular to the window opening direction is provided in the threaded body at the window opening. Both sides of the internal connecting support beam are respectively connected to the polygonal hollow cavity to form a through channel.

The ratio of the width to height of the window located on the side wall of the threaded body is 1:(2-5); the ratio of the height of the internal connecting support beam to the height of the window is 1:(1.5-3.0); the ratio of the height of the window to the total height of the threaded body is 1:(3-8).

The nail head is in the shape of a cone, a hemisphere or a hemi-ellipsoid. The internal microstructure of the nail head is not strictly limited and can be a dense structure or a structure containing micropores.

The ratio of the height of the nail cap, the height of the threaded body and the height of the nail head is 1:(8-15):(1.2-6.0).

In the third aspect, the present scheme provides a multifunctional hollow porous screw, which includes: a screw body made of calcium silicate ceramics, the screw body includes a holding nail cap, a threaded body and a nail head arranged in sequence, the magnesium ions and zinc ions in the calcium silicate ceramics are gradiently distributed along the direction of the axis of the screw body, and there are polygonal hollow cavities that are mutually interconnected and on the same axis inside the holding nail cap and the threaded body, the side wall of the threaded body includes a plurality of through micropores discretely distributed on the thread groove surface, and a window is provided on the side wall where the threaded body and the nail head are connected.

Specifically, the multifunctional hollow porous screw includes: a screw body made of calcium silicate ceramics, the screw body includes a gripping nail cap, a threaded body and a nail head arranged in sequence, and the magnesium ions and zinc ions in the calcium silicate ceramics are distributed in a gradient along the axis of the screw body.

The content of at least two inorganic magnesium ions and zinc ions in the multifunctional hollow porous screw of the present invention gradually increases or decreases in the screw material along the direction from the screw cap to the screw head, ensuring that different parts produce biological functions with specific requirements.

In some embodiments, if there is a high content of magnesium ions in the nail head and the thread body, they are released to the part that is in the closest contact with the host tissue to effectively prevent and control postoperative inflammatory side effects; conversely, if there is a high content of zinc ions in the nail cap holding part, they are released to the part that is more easily exposed to the soft tissue or the outside world to prevent the greater risk of infection in this part. In other words, the content of magnesium ions gradually increases along the direction from the nail cap holding to the nail head, and the content of zinc ions gradually decreases along the direction from the nail cap holding to the nail head.

Specifically, the molar percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the nail cap portion, expressed as oxides of magnesium, zinc, calcium and silicon, are not higher than 6% and 23% respectively; the molar percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the nail head portion, expressed as oxides of magnesium, zinc, calcium and silicon, are not higher than 23% and 6% respectively; the molar percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the threaded body portion, expressed as oxides, are between the contents of magnesium and zinc in the nail cap and the nail head portion, respectively.

In this scheme, a multifunctional hollow porous screw can be manufactured by three-dimensional printing technology. Correspondingly, the gradient distribution of different functional ions in the screw can be adjusted by selecting the ceramic components or relative proportions when preparing the printing ceramic slurry.

The polygonal hollow cavity can be selected as one of a quadrilateral, a pentagon or a hexagon, and the ratio of the side length of the polygonal hollow cavity to the outer diameter of the thread body is 1:(3.0-8.0). Two adjacent through micro-holes are arranged along the thread groove rotated 450°.

In some embodiments, the size of the through micropores is 300-800 microns. The width of the thread groove surface of the threaded body is 800-1200 microns, and the width of the top surface of the thread protrusion is 10%-90% of the width of the thread groove surface. The angle between the thread groove surface and the side wall of the thread protrusion is 90°-135°. There is no strict restriction on the height of the thread protrusion, and the preferred height of the thread protrusion is 600-1800 microns. The ratio of the diameter of the thread groove circular surface of the threaded body to the outer diameter of the gripping nail cap is 1:(1.2-3.0).

The through micropores may be in the shape of a circular, square, hexagonal or elliptical hole or any combination thereof. That is, the through micropores may be micropores of different hole sizes or different hole shapes. An inner connecting support beam perpendicular to the window opening direction of the window is provided in the threaded body inside the window opening, and the two sides of the inner connecting support beam are respectively connected to the polygonal hollow cavity.

The width/height ratio of the window located on the side wall of the threaded body is 1:(2-5); the ratio between the height of the internal connecting support beam and the height of the window is 1:(1.5-3.0); the ratio between the height of the window and the total height of the threaded body is 1:(4-8).

The nail head is in the shape of a cone, a hemisphere or a semi-ellipsoid, and the ratio of the height of the holding nail cap 11, the height of the threaded body and the height of the nail head is 1:(8-15):(1.2-6.0).

In a fourth aspect, the present invention provides a method for preparing a multifunctional hollow porous screw, comprising the following steps:

a) stirring and mixing calcium silicate ceramic ultrafine powder with different magnesium and zinc contents with photosensitive resin to form different batches of printing slurries, wherein the magnesium ions and zinc ions in different batches of printing slurries are different, adding at least one printing slurry into the printing pool according to a pre-designed gradient distribution rule for three-dimensional printing, and immediately pouring the next batch of printing slurry into the printing pool when the slurry is about to be exhausted and maintaining printing, wherein the gradient distribution rule is that the magnesium ions and the zinc ions are distributed in a gradient along the direction of the axis of the screw body, until the three-dimensional model of the multifunctional hollow porous screw is printed, the printed material is rinsed, the uncured resin is discharged, and the composite is dried for standby use;

b) calcining the composite obtained in step a) at 1050°C-1450°C for 1-6 hours, with a heating rate of 1°C-6°C per minute during the sintering process; when the temperature rises to 400°C-600°C, keeping the temperature for 30-90 minutes for degreasing; and cooling naturally after the high-temperature sintering is completed to obtain a multifunctional hollow porous screw.

In the preparation method, calcium silicate ceramic ultrafine powders with different magnesium and zinc contents and photosensitive resin are stirred and mixed evenly at a mass ratio of 100:(50-95). The multifunctional hollow porous screw three-dimensional model includes a gripping nail cap/thread body and a nail head arranged in sequence, and magnesium ions and zinc ions are distributed in a gradient along the axis of the screw body.

In the 3D printing technology, a 3D model of a multifunctional hollow porous screw with redundant design is firstly made according to computer modeling, and then 3D printing is performed using a ceramic light-curing printer.

The types of other ions contained in the calcium silicate bioceramic are not strictly limited. In addition to magnesium and zinc ions, sodium ions, potassium ions, strontium ions, borate ions or phosphate ions may also be contained.

The degree of crystallinity of the multifunctional hollow porous screw is not strictly limited, and it can be a completely crystallized bioactive ceramic, or a bioactive glass-ceramic containing no more than 20% of a glass phase.

The internal microstructure of the nail head of the multifunctional hollow porous screw is not strictly limited, and can be a highly dense structure or a porous structure. The pore morphology, pore size and pore penetration of the porous structure are not strictly limited either.

There is no strict restriction on whether the inner and outer surfaces of the multifunctional hollow porous screw of the present invention are subjected to secondary modification. A modified layer may be formed on the inner and outer surfaces of the screw, or other functional substances may be injected into the hollow cavity to further improve the various functions of the screw.

The multifunctional hollow porous screw of the present invention has no strict restrictions on the chemical composition of the screw. Other inorganic bioactive ceramics or bioactive glass components with sintering-aiding properties can be added to the calcium silicate ceramic slurry before printing to enhance the sintering of the screw or further improve the comprehensive mechanical properties of the screw. There is no strict restriction on whether the magnesium and zinc in the calcium silicate ceramic are in a coexisting form. Zinc ions and magnesium ions can be co-doped into wollastonite, and zinc ions can be further doped into magnesium ion-doped wollastonite, whitsonite, magnesium-rich whitsonite, magnesium-rich magnesium-whitsonite, magnesium-rich magnesium-rich magnesium-whitsonite, magnesia chrysogenite, and magnesium-rich magnesia chrysogenite. Magnesium ions can also be doped into zinc chrysogenite or zinc-rich zinc chrysogenite, thereby forming a calcium silicate-based screw composed of a gradient distribution of magnesium ions and zinc ions.

The multifunctional hollow porous screw of the present invention has no strict restrictions on the thread continuity of the thread body of the screw. It can be a continuous thread formed along the outer wall of the thread body, or a discontinuous interrupted thread, so that the thread groove can be quickly integrated with the host tissue.

In the fifth aspect, the present invention provides an application method of a multifunctional hollow porous screw, comprising the following steps: it can be applied to the fields of instrument internal fixation, wire anchoring, drug loading or nutrient loading sustained release of bone or joint injuries, and improve or enhance bone injury repair, soft tissue fixation or healing, biomechanical correction and/or nutrient delivery in pathological bone tissue sites.

The multifunctional hollow porous screws provided by this solution have the following advantages

1) In terms of composition, the degradation rate of high-temperature calcined ceramics or glass-ceramics can be optimized by utilizing calcium silicate ceramics or glass-ceramics with functional ion dosage and combination relationship, which is beneficial to the synergistic optimization of the mechanical function requirements and biological effect requirements of the screws under different clinical indications.

2) Structurally, the multifunctional hollow porous screw prepared by the 3D printing manufacturing process has hollow cavities along the axis of the holding nail cap and the threaded body, which is conducive to surgical implantation. The discretely distributed micropores on the side wall of the threaded body are conducive to the growth of new tissue and the release of functional substances loaded in the hollow cavity. The optimized design of the discrete spacing of the micropores can not only ensure that the anti-fracture mechanics of the screw is not affected, but also help to enrich the comprehensive performance and efficacy such as functional characteristics and mechanical pull-out resistance.

3) In terms of biological effects, the slow systemic release of functional ions with gradient distribution can enhance the unique functional requirements of local anti-infection and anti-inflammatory responses, and significantly promote vascularization, bone regeneration and efficient bone integration, and is beneficial to prevent risks such as postoperative loosening of screws and rapid decrease in holding force.

4) In terms of operability, the multifunctional hollow porous screws precisely manufactured by 3D printing have precisely controllable thread microstructures in any part, and will not cause local micro-damage or stress concentration to the screws during conventional thread construction. They can also be directly sterile packaged after high-temperature calcination, reducing the risk of screw contamination.

Compared with the prior art, this technical solution has the following characteristics and beneficial effects:

The multifunctional hollow porous screw adopts the functional ion gradient distribution method, making full use of the unique inflammatory response control function and anti-bacterial infection function of different functional magnesium and zinc ions. The content levels of magnesium and zinc ions in different parts of the screw achieve the optimization of multiple biological functions, and can further regulate the sintering performance, biodegradability and fracture resistance of calcium silicate ceramics. In addition, the multifunctional hollow porous screw provided by this scheme has a through microporous structure on the side wall of the threaded body. The through microporous structure combined with the functional ion gradient distribution can overcome the problem that the gripping nail cap part in contact with the soft tissue outside the bone is most likely to induce infection risk, and strengthen the efficient and firm integration ability of the threaded body and bone tissue, significantly improve the anti-pullout ability, and effectively enhance the function of the entire screw.

The benefits of functional ion gradient distribution are:

(1) The multifunctional hollow porous screw provided in this scheme contains a higher dose of zinc ions in the calcium silicate ceramic at the gripping nail cap, which can effectively prevent bacteria from penetrating into the interior from the interface between soft and hard tissues.

(2) The multifunctional hollow porous screw provided in this scheme contains a high level of magnesium ions in the calcium silicate ceramics at the screw head and the thread body, which can effectively control the inflammatory reaction in the thread locking area after screw implantation, so that the interface tissue will not loosen the screw due to excessively long inflammatory reaction.

(3) The reverse gradient change of the content of magnesium and zinc ions in the screw can also effectively solve the problem of stable mechanical properties of the entire screw, significantly improve the brittleness of conventional pure calcium silicate ceramics, and enhance the fracture toughness and fracture resistance.

The benefits of the through-hole microporous structure are:

(1) Discretely distributed microchannels are provided on the side wall of the threaded body and are completely connected with the internal hollow cavity, which can facilitate the rapid growth of new tissue into the hollow cavity, enhance the early integration and bonding strength between the screw and the host tissue, reduce the interface integration requirements that rely solely on thread locking to resist pull-out, and facilitate the medium- and long-term pull-out resistance, as well as the release of the guest substance loaded in the hollow cavity to the outer wall of the threaded body and the performance of its function.

(2) By opening a window on the side wall of the threaded body and providing a connecting support beam inside, the application of this type of screw can be expanded to soft tissue fixation in orthopedic surgery, fixing surgical wires with the help of the connecting support beam and the hollow cavity in the threaded body, repairing ligaments, and ligament reconstruction.

(3) The polygonal hollow cavity is provided in the two parts of the screw cap and the threaded body, which can facilitate the rotation of the surgical tool to implant the screw, and avoid the risk of conventional screws with grooves on the top cap surface, which may cause stress concentration at the grooved part when the surgical tool rotates the screw to implant the screw into the tissue, resulting in cracking and failure of the grooved part.

In addition, this solution can adjust the complete degradation time of the screws by adjusting the magnesium and zinc ion content in the calcium silicate ceramics, thereby adapting to different clinical indications. It can comprehensively solve the material mechanics, degradation rate, and coordinated prevention and control of inflammation, infection and other functional requirements of instruments or tissue fixation involved in the repair of soft and hard tissue injuries of a large number of bones and joints in clinical practice.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a structural diagram of a multifunctional hollow porous screw according to a preferred embodiment of the present invention;

FIG2 is a front view of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG3 is a left view of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG. 4 is a top view of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG5 is a bottom view of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG6 is a front cross-sectional view of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG. 7 is a left side cross-sectional view of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG8 is a cross-sectional view of the window opening portion of the threaded body of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG9 is a top view of a cross-sectional view of the threaded body of a multifunctional hollow porous screw according to a preferred embodiment of the present invention.

FIG10 is an XRD diagram of magnesium-calcium silicate ceramic powder of a multifunctional hollow porous screw of a preferred embodiment of the present invention. A: 12.1% magnesium substituted calcium ion doped wollastonite; B: 7.6% magnesium substituted calcium ion doped wollastonite; C: 4.8% magnesium substituted calcium ion doped wollastonite. * Wollastonite.

FIG11 is an XRD diagram of zinc-calcium silicate ceramic powder of a multifunctional hollow porous screw of a preferred embodiment of the present invention. A: 4.0% zinc substituted calcium ion doped wollastonite; B: 7.4% zinc substituted calcium ion doped wollastonite; C: 11.2% zinc substituted calcium ion doped wollastonite. * Wollastonite.

FIG. 12 is a structural diagram and a bottom view of a multifunctional hollow porous screw having a cylindrical holding nail cap according to a preferred embodiment of the present invention.

13 is a structural diagram and a bottom view of a multifunctional hollow porous screw having an elliptical cylindrical holding nail cap according to a preferred embodiment of the present invention.

FIG. 14 is a structural diagram and a bottom view of a multifunctional hollow porous screw having a hemispherical nail head according to a preferred embodiment of the present invention.

FIG. 15 is a structural diagram of a multifunctional hollow porous screw having square micropores on the threaded groove surface of a threaded body according to a preferred embodiment of the present invention.

Detailed ways

The following will be combined with the 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 described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

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 multi-dependent or redundant. Where a disclosure is made with respect to features relating to a particular aspect of the invention (e.g., the multifunctional hollow porous screw of the invention), the disclosure should also be considered to apply to any other aspect of the invention (e.g., the method of the invention).

Example 1: Preparation of multifunctional hollow porous screws [Structural model is shown in Figures 1-9]

1) Three magnesium-doped wollastonite ceramic powders (particle sizes of all less than 30 μm, XRD analysis patterns shown in FIG10) with magnesium replacing calcium molar percentages of 12.1%, 7.6% and 4.8% respectively and three zinc-doped wollastonite ceramic powders (particle sizes of less than 20 μm, XRD analysis patterns shown in FIG11) with zinc replacing calcium molar percentages of 4.0%, 7.4% and 11.2% respectively were stirred and mixed evenly at a powder-resin mass ratio of 2:1 to form 6 groups of photocurable printing slurries, and then part of the slurries of two groups of wollastonite ceramics in which the magnesium and zinc substitution doping rates of calcium were 4.8% and 11.2% respectively were taken and mixed at a mass ratio of 1:4 and poured into the printing slurry pool, and the multifunctional hollow porous The screw structure model (as shown in Figures 1-9) is enlarged in proportion with redundant design, and the light-curing printer is turned on. When the spherical gripping nail cap 11 containing the hexagonal hollow cavity is partially printed, the residual slurry is sucked out, and the slurry of two groups of wollastonite ceramics with magnesium and zinc replacing calcium doping rates of 7.6% and 7.4% respectively is poured into the slurry pool in a ratio of 1:1. The printing is continued until the rectangular window 4 on the side wall of the threaded body 12 begins to be printed, and the slurry of two groups of wollastonite ceramics with magnesium and zinc replacing calcium doping rates of 12.1% and 4.0% respectively is poured into the slurry pool in a ratio of 3:1 until the nail head 13 is printed, and then the print is removed and the uncured slurry is rinsed off with tap water.

2) The multifunctional hollow porous printed material obtained in step 1) is dried at 60°C for 12 hours, kept at 480°C for 45 minutes at a heating rate of 2°C/min for degreasing, and then continued to heat to 1150°C for sintering for 2 hours, and then naturally cooled, thereby obtaining a multifunctional hollow porous screw with magnesium and zinc distributed in reverse gradient along the axis of the screw body. It can be seen from general observation that the hollow cavity in the screw is a regular hexagon, the gripping cap is a spherical structure, and the nail head is a cone. After testing, the total length of the multifunctional hollow porous screw after sintering is 17.6mm, the height of the holding top cap part is 2.0mm, the height of the nail head is 2.6mm, the height of the threaded body 12 is 13.0mm, the thread protrusion circle diameter of the threaded body is 5.3mm, the thread groove surface circle diameter of the threaded body is 4.2mm, the side wall window width and height of the threaded body are 2.3mm and 4.8mm respectively, and the side length of the hexagonal hollow hole cavity inside the holding top cap and the threaded body is 1.8mm.

Example 2: A better multifunctional hollow porous screw [the structural model is shown in Figure 12]

The preparation method is the same as that of Example 1, except that: in step 1), magnesium-rich magnesia chalcedony ultrafine powder (the percentage of magnesium oxide to the total molar percentage of calcium, magnesium, and silicon oxides is 21.7%) is used to replace the magnesium-doped wollastonite ceramic ultrafine powder with a molar percentage of 12.1% of magnesium replacing calcium, and white calcite is used to replace the magnesium-doped wollastonite ceramic ultrafine powder with a molar percentage of 7.6% of magnesium replacing calcium, and the structural model of the hollow porous screw with a cylindrical gripping nail cap shown in Figures 12A and 12B (other structures are the same as those of Example 1) is used as a printing model, and redundant design is performed to enlarge the scale in proportion, so that a multifunctional calcium silicate hollow porous screw with high activity, degradability, anti-infection, and anti-inflammatory reaction can be obtained with reverse gradient distribution of magnesium and zinc functional ions. It can be seen from general observation that the gripping top cap maintains a cylindrical morphology, and the other parts are consistent with the morphology of Example 1.

Example 3: A better multifunctional hollow porous screw [the structural model is shown in Figure 13]

The preparation method is the same as that of Example 1, except that: in step 1), the zinc-doped wollastonite ceramic ultrafine powder is used instead of the zinc-doped calcium ultrafine powder with a molar percentage of 11.2%, and the structural model of the hollow porous screw with an elliptical cylindrical gripping nail cap shown in Figures 13A and 13B (other structures are the same as those of Example 1) is used as a printing model, and a redundant design is performed to enlarge the scale in proportion, and other conditions remain unchanged, so that a high mechanical reliability, degradable, multifunctional calcium silicate hollow porous screw with reverse gradient distribution of magnesium and zinc functional ions can be obtained. It can be seen from general observation that the gripping top cap maintains an elliptical cylindrical morphology, and the other parts remain consistent with the morphology of Example 1.

Example 4: A better multifunctional hollow porous screw [the structural model is shown in Figure 14]

The preparation method is the same as that of Example 1, except that: in step 1), the magnesium-doped wollastonite ceramic powder is replaced with ultrafine powders of magnesia chalcedony, magnesia calcite and leucistic calcite, respectively, with the molar percentages of magnesium replacing calcium being 12.1%, 7.6% and 4.8%, respectively, and the structural model of a hollow porous screw with square holes in the discretely distributed micropores in the thread groove surface on the side wall of the threaded body shown in FIG. 14 (other model structures are the same as those of Example 1) is used as a printing model, and a redundant design is performed to enlarge the scale in proportion, and other conditions remain unchanged, so that a highly active, degradable and multifunctional calcium silicate hollow porous screw with reverse gradient distribution of magnesium and zinc functional ions can be obtained. It can be seen from general observation that the discrete micropores in the thread groove surface on the side wall of the threaded body are square, and the other parts are consistent with the morphology of Example 1.

Example 5: A better multifunctional hollow porous screw [the structural model is shown in Figure 15]

The preparation method is the same as that in Example 1, except that: in step 1), the magnesium-doped wollastonite ceramic powder with a molar percentage of 12.1%, 7.6% and 4.8% of magnesium-substituted calcium is replaced by ultrafine powders of magnesia chalcedony, magnesia calcite and leucistic calcite, respectively, and the zinc-doped wollastonite ceramic powder with a molar percentage of 11.2% of zinc-substituted calcium is replaced by ultrafine zinc chalcedony, and the structural model of the hollow porous screw with a hemispherical nail head shown in FIG15 (other structures are the same as those in Example 1) is used as a printing model, and a redundant design is performed to enlarge the scale in proportion, and other conditions remain unchanged, so that a highly active, degradable multifunctional calcium silicate hollow porous screw with reverse gradient distribution of magnesium and zinc functional ions can be obtained. It can be seen from general observation that the nail head is hemispherical, and the other parts are consistent with the morphology of Example 1.

Example 6: A better multifunctional hollow porous screw [a window is opened on the side wall of the threaded body near the nail cap holding part]

The preparation method is the same as that of Example 1, except that: in step 1), a structural model of a hollow porous screw with a window on the side wall of the threaded body close to the gripping nail cap (other structures are the same as those of Example 1) is used as a printing model, and other conditions remain unchanged, and a high mechanical reliability, degradable, multifunctional calcium silicate hollow porous screw with reverse gradient distribution of magnesium and zinc functional ions can be obtained. A general observation shows that the window is 2.2 mm away from the gripping nail cap, and the other parts are consistent with the morphology of Example 1.

Example 7: A better multifunctional hollow porous screw [Preparation of multifunctional hollow porous screw with high mechanical reliability by two-stage sintering]

The preparation method is the same as that in Example 1, except that: in step 2), the washed printed material is dried at 60°C for 12 hours, degreased at 450°C for 45 minutes at a heating rate of 2°C/min, then heated to 1150°C and sintered for 20 minutes, then cooled to 1080°C within 10 minutes and kept warm for 2.5 hours, and then naturally cooled, thereby obtaining a high mechanical reliability, degradable, multifunctional hollow porous screw with reverse gradient distribution of magnesium and zinc along the axis of the screw.

Example 8: Implementation of animal model validity and reliability verification [Beagle dog femoral screw bone integration, anti-pullout and autonomous anti-side effect risk assessment experiment]

Take a 9-month-old male beagle dog, weighing 13±2Kg; after intraperitoneal anesthesia is performed at a dosage of 10% chloral hydrate 2.5ml/1000g, the back skin is prepared, and the drape is routinely disinfected. Take a longitudinal incision in the femoral condyle, about 3cm long, free the subcutaneous tissue, expose the fascia, cut to the surface of the muscular layer, cut about 2.5cm long, form a long wound, prepare a threaded hole with a metal screw, and then rotate the magnesium and zinc gradient distribution calcium silicate salt screws prepared in Examples 1, 2, 3, and 4 into the femur at this position. Suture the incision, stop bleeding carefully, clean the wound and close the wound layer by layer, and suture the skin. Penicillin is injected intramuscularly after surgery. Feed under normal conditions. The beagles were killed after 2, 6, 12, and 26 weeks, and the implantation site and surrounding tissues of the femoral screws of the beagles were observed. It was found that the tissues around the screws of Examples 1, 2, 3, and 4 were normal, and there was no severe inflammatory reaction in the early stage of 2 weeks after surgery. X-ray and microCT reconstruction analysis showed that tight bone integration occurred 2 to 6 weeks after implantation, and the screws gradually degraded at 12 and 26 weeks after surgery. The material and tissue interface were well integrated with each other, especially a large amount of ossification occurred 26 weeks after hollow cavity surgery, indicating that new bone was bone-conducted to the hollow cavity through the side wall micropores; anti-pullout tests at various time points showed that a high anti-pullout function was achieved 2 weeks after surgery, the highest anti-pullout force level was achieved at 6 and 12 weeks, the screws were partially degraded at 26 weeks, the anti-pullout ability was still maintained at a high level, and the screws broke during the pull-out process, indicating that the bone integration strength was extremely high.

It can be seen from the above embodiments that the hollow porous multifunctional screw of the present invention can perform efficient bone integration and long-term anti-pullout function on the injured part of the femur, and can autonomously control inflammatory response and prevent infection. The screw will also be gradually biodegraded, and has application value and significant technical effects in various bone reconstruction internal fixations.

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

Claims (10)

1. A multifunctional hollow porous screw, comprising: the screw comprises a screw body composed of calcium silicate ceramics, wherein the screw body comprises a holding nut, a thread body and a nail head which are sequentially arranged, and magnesium ions and zinc ions in the calcium silicate ceramics are distributed in a gradient manner along the axis direction of the screw body.

2. The multifunctional hollow porous screw of claim 1, wherein the content of magnesium ions gradually increases along the direction of holding the nut to the head, and the content of zinc ions gradually decreases along the direction of holding the nut to the head.

3. The multifunctional hollow porous screw according to claim 1, wherein the mole percentages of magnesium, zinc in the calcium silicate ceramic corresponding to the grip nut portion are not higher than 6% and 23%, respectively, expressed as oxides of magnesium, zinc, calcium, silicon; the mole percentages of magnesium and zinc in the calcium silicate ceramic corresponding to the nail head part expressed by oxides of magnesium, zinc, calcium and silicon are not higher than 23% and 6%, respectively.

4. The utility model provides a multi-functional cavity porous screw, its characterized in that comprises the screw body of calcium silicate pottery, the screw body is including holding the nail cap, screw thread body and the pin head of arranging in proper order, magnesium ion, zinc ion in the calcium silicate pottery is gradient distribution along the axis direction of screw body, hold the nail cap with inside polygonal hollow bore that has mutually to link up and be in the same axis of screw thread body, including a plurality of discrete through micropore that distribute on the screw thread recess face on the lateral wall of screw thread body, screw thread body with be equipped with on the lateral wall of pin head phase connection position and open the window, be provided with in the screw thread body of opening the window inside with open window direction vertically interior supporting beam, interior supporting beam's both sides respectively with polygonal hollow bore link up.

5. The multifunctional hollow porous screw of claim 4, wherein two adjacent through micro holes are arranged along the threaded groove by 450 °.

6. The multifunctional hollow porous screw of claim 4, wherein the width of the top surface of the thread protrusion of the thread groove surface of the thread body is 10% -90% of the width of the thread groove surface, and the included angle between the thread groove surface and the side wall of the thread protrusion is 90 ° -150 °.

7. The multifunctional hollow porous screw according to claim 4, wherein the ratio of width/height of the window at the side wall of the threaded body is 1 (2-5); the ratio of the height of the internal connection supporting beam to the height of the window is 1 (1.5-3.0); the ratio of the height of the open window to the total height of the screw thread body is 1 (3-8).

8. The preparation method of the multifunctional hollow porous screw is characterized by comprising the following steps of:

a) Uniformly stirring and mixing the calcium silicate ceramic ultrafine powder with different magnesium and zinc contents with photosensitive resin to form printing slurry of different batches, adding at least one printing slurry into a printing pool for three-dimensional printing according to a preset gradient distribution rule, immediately pouring the next printing slurry when the slurry is about to be exhausted, and maintaining printing, wherein the gradient distribution rule is that magnesium ions and zinc ions are distributed in gradient along the axis direction of a screw body until the printing of the multifunctional hollow porous screw three-dimensional model is completed, flushing a printed matter, removing uncured resin, and drying a compound for later use;

b) Calcining the compound obtained in the step a) at the high temperature of 1050-1450 ℃ for 1-6 hours, wherein the heating rate in the sintering process is 1-6 ℃ per minute, preserving heat for 30-90 minutes when the temperature is increased to 400-600 ℃ for degreasing, and naturally cooling after the high-temperature sintering is finished to obtain the multifunctional hollow porous screw.

9. The method for preparing the multifunctional hollow porous screw according to claim 8, wherein the multifunctional hollow porous screw three-dimensional model comprises a holding nut, a threaded body and a nail head which are sequentially arranged, and magnesium ions and zinc ions are distributed in a gradient manner along the axis direction of the screw body.

10. Use of a multifunctional hollow porous screw according to any of claims 1 to 7 for in-instrument fixation of bone or joint injuries, wire anchoring, drug or nutrient delivery sustained release, improving or enhancing bone injury repair, soft tissue fixation or healing, biomechanical correction and/or nutrient delivery at pathological bone tissue sites.