CN114404656A

CN114404656A - Core-shell structure fiber functional inorganic biomaterial, preparation method and application

Info

Publication number: CN114404656A
Application number: CN202210157133.4A
Authority: CN
Inventors: 杨贤燕; 苟中入
Original assignee: Zhejiang Bogu Medical Technology Co ltd
Current assignee: Zhejiang Bogu Medical Technology Co ltd
Priority date: 2022-02-21
Filing date: 2022-02-21
Publication date: 2022-04-29

Abstract

The application provides a core-shell structure fiber functional inorganic biomaterial, a preparation method and application, wherein the preparation method comprises the steps of mixing bioactive inorganic powder and pore-forming particles with different components with a liquid or semi-fluid dispersing agent respectively to form slurry, forming fibers from the slurry through a core-shell nozzle, and then soaking, washing, drying and calcining the collected fibers. The length and the form of the core-shell structure fiber functional inorganic biomaterial, and the thickness, the micropore size and the porosity of each layer component can be adjusted. The core-shell structure fiber functional inorganic biomaterial can release various functional inorganic ions, prevent infection, control inflammation, promote bone injury and adjacent soft tissue cooperative regeneration and repair, and can be applied to human skeletal muscle system tissue regeneration and repair medicine.

Description

Core-shell structure fiber functional inorganic biomaterial, preparation method and application

Technical Field

The application relates to biomedical materials, in particular to the field of bone and adjacent soft tissue injury regeneration repair and prevention and control of side reaction problems, and particularly relates to a core-shell structure fiber functional inorganic biomaterial, a preparation method and application.

Background

The high-efficiency complete healing and regeneration repair of skeletal muscle injuries and defects caused by various reasons are the current clinical problems. In the aspect of bone injury repair and reconstruction, autogenous bone or allogeneic bone transplantation or animal bone deep processing products are often adopted for filling repair. Over the last 20 years, successive studies have demonstrated that calcium-silicon (CaO-SiO)₂) Inorganic active ceramic, glass or glass-ceramic material as matrix, which can be directly combined with bone tissue osseointegratively and regulate immune system (Huang Y et al, Acta Biomater 2018,66:81-92), even can take special action with soft tissue such as epithelium, dermis, muscle, periosteum and the like to promote healing and repair (Zhou Y et al, Adv health Mater 2018,1800144; lv F et al, Acta Biomate 2017,60: 128-143; han Y et al, J Mater Chem B2017, 5(18): 3315-3326). Calcium-phosphorus (CaO-P)₂O₅) Inorganic active materials such as Hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP) and biphase calcium phosphate ceramics constructed by compounding the materials are sequentially applied to orthopedics clinic, wherein organic-inorganic hybrid composite materials are formed by compounding sintered blocks, particles or collagen through bionic deposition. However, the degradation rate and activity of these calcium phosphate materials are difficult to regulate, so that the efficiency of stimulating tissue regeneration repair is difficult to regulate, and especially, the materials have serious defects in the control of infection risks and the control contract regulation of various chronic inflammations.

Secondly, although amorphous glassy materials represented by 45S5 glass have excellent effects in bonding strength with host bone tissues and promoting proliferation and differentiation of cells in soft and hard tissues, and dissolved silicon, calcium, phosphorus and the like can activate transcription factors and cell cycle regulatory factors of osteoblasts, fibroblasts, epithelial cells, vascular endothelial cells and the like, the dosage of active ions dynamically released by these bioactive glass particles is difficult to control autonomously, and thus, the early inflammation is likely to develop continuously, and the degradation of particles is difficult to match with the process of bone regeneration and repair in bone injury. Moreover, the soft tissue wound healing material compositely constructed by the granular material, hydrogel, vaseline and the like also faces the problem that the dosage of degraded and released ions is difficult to control. At present, different substances containing silicon, calcium, phosphorus and the like are mechanically combined and screened in various preparation methods of inorganic ceramic or glass biomaterials, and inorganic powder particles with different sizes are prepared in a mechanical ball milling mode, so that the preparation method is difficult to control the material micro-granularity, the degradation speed of material products and the dissolution speed of bioactive ions, and an active material with the component compatibility required for generating the optimal stimulation on soft and hard tissue regeneration and repair cells is difficult to obtain (Yu Q and the like, J Mater Chem B.2019,7: 5449-.

With the development of materials science, cell biology, immunology and regenerative medicine, it is found that some microelements such as silicon, strontium, magnesium, copper, zinc, boron and the like have multiple biological functions, even can promote the regeneration repair or healing of bone tissues and soft tissues, magnesium, zinc, copper and the like can prevent and control tissue infection caused by pathogenic bacteria proliferation, and silicon, boron and the like can even regulate inflammatory reaction in wounds and promote vascularization. Some researches and clinical applications prove that the bone regeneration and repair effects of the material can be improved after silicon, strontium, magnesium, zinc and boron are mixed into the calcium phosphate material. However, the dynamic release dosage level of these functional active ions directly determines the relevant cellular activity and metabolism level, and too high dosage of copper, zinc and other ions may cause cytotoxicity and even cause other ions to be dysregulated in physiological metabolism.

Recently, the research of the inventor finds that the inorganic near-spherical microparticle composite material developed by a coaxial core-shell structure type packaging mode can control the degradation rate of the inner core layer component, and the osteogenesis efficiency can be adjusted through the optimized configuration of the degradation characteristics of the inner and outer layer components (Liu L and other J Am Ceram S DEG C2016; 99: 2243; Ke X and other, ACS Appl. Mater Interf.2017; 7: 24497; Fu J and other, Tissue Eng. part A.2019; 25: 588; Edem Prince G-A and other, Mater Sci Eng C.2019; 100: 433). The Chinese patent ZL 201310148344.2 of the inventor discloses microsphere material of core-shell structure calcium silicate-calcium phosphate bioactive ceramics, but the microsphere lacks effective structure maintenance and cell rapid growth in a larger bone injury space, the porosity in a tightly packed microsphere particle pack is low (less than 35%), and especially the microsphere material has insufficient design on multi-tissue healing and multifunctionality. In general, the application of the conventional core-shell structure type particle material has limitations, and there are major problems such as:

1) in the initial stage of the approximately spherical core-shell structure particle material in the wound tissue, the release dosage of active ions depends on the degradability of shell components and the through structure of micropores in the shell, and the active ions can only grow new tissues inwards through the degraded shell components or the degraded through micropores (the exposure degree of the core components is restricted);

2) the method is extremely difficult to realize the random wrapping of a plurality of inorganic components from inside to outside or in parallel arrangement, and a two-dimensional and three-dimensional (fiber network, fiber sponge, fiber bracket and other forms) continuous porous skeleton structure can not be directly formed in a long way, and a certain mechanical support is exerted, so that the difficulty is caused on the filling of large-volume or area bone injury and the stability of particles (the particles are easy to roll and slide);

3) the regulation and control capability on the distribution and content level of the components in the core layer is poor, so that the degradation efficiency of the components in different layers in the core-shell structure can be seriously influenced;

4) the bioactive ceramic granular material has serious insufficient effects of preventing and controlling bone wound complications such as infection, inflammation and the like and synergistically promoting the regeneration and healing of the injury of adjacent soft tissues of bones.

Although the electrospinning technology can manufacture inorganic nano-fibers, the fibers are often dependent on the conductivity of a receiving carrier, the formed fibers are too fine, the space of the stacked pore channels is extremely low, and the difficulty of rearranging the fibers after the fibers are deposited on the carrier is large due to a thin film material formed by electrospinning. According to the report of clinical application literature, a new generation of inorganic bioactive material preparation technology needs to be developed, so that the chemical components of inorganic bioactive substance components from micro-scale to macro-scale level can be accurately regulated and controlled, the distribution of each component can be accurately controlled, the internal microstructure of a specific component can be finely cut, simple and convenient post-processing treatment can be performed according to the requirements of clinical bone and adjacent soft tissue injury adaptive syndrome characteristics, particularly, the inorganic bioactive material can be simply sheared, stacked, woven or automatically formed into a sponge type to form a zero-dimensional, one-dimensional, two-dimensional and three-dimensional universal biological material, and the material has the following requirements:

1) according to the requirements of defect size and shape, the inorganic bioactive material can be cut, woven or stacked very simply, conveniently and efficiently, the structural characteristics between the composition and the structure of any local level of the material cannot be damaged in the post-treatment process, the multi-level structure, the biological function or the efficacy of the material in any scale level are maintained, the bone injury can be filled completely and efficiently, and a completely through pore canal network is generated;

2) any bone wound has inflammatory reaction and infection risk, so the inorganic bioactive material has the anti-infection and inflammation control capabilities independent of conventional drugs, and avoids the abuse or drug resistance problems of various drugs;

3) any bone injury problem faces bone wounds with different degrees and adjacent soft tissue combined injury, so that inorganic bioactive materials are required to not only solve the regeneration and repair of the bone injury, but also perform the regeneration and reconstruction activity on muscles, periosteum, periodontal ligament, cartilage calcified layer and the like by the aid of the materials implanted into the bone injury, and especially control the possible chronic inflammatory reaction of the adjacent soft tissue of the bone injury;

4) the degradation rate of each component of the inorganic bioactive material is not shielded or shielded by any other component, the inorganic bioactive material can be independently degraded, and a space provided after degradation can be rapidly filled with new bones;

5) the dosage (concentration) of inorganic metal ions and acid radical ions released by the degradation of each chemical component of the inorganic bioactive material can be widely adjusted, and the substances can synergistically perform infection prevention, inflammation control and tissue regeneration promotion to achieve the optimal effect, thereby properly solving the long-standing clinical problem.

Therefore, according to the prior patent technology, there is an urgent need to search for a functional inorganic bioactive material which satisfies the requirements of clinical rapid regeneration and healing of various human skeletal muscle system wounds, complete repair and whole-course prevention and control of various side reactions and complications in terms of composition, micro-scale to macro-scale, especially biological effect of the inorganic bioactive material, realizes rapid inhibition and even killing of pathogenic bacteria activity, immune cells regulate and repair polarization to tissue regeneration, and active regulation and control of proliferation and differentiation of tissue-related (stem) cells, activates up-regulation expression of genes related to tissue regeneration, achieves the biological activity of rapid regeneration and repair of new tissues in the wounds, especially the release dosage of functional active ions can be cut through the design of component distribution, content and microstructure of the material, the best effect matched with the best requirement on wound repair is achieved.

Disclosure of Invention

The embodiment of the application provides a core-shell structure fiber functional inorganic biomaterial, a preparation method and an application, aiming at the problem of regulating the release dosage of an active substance for bone injury and adjacent soft tissue cooperative regeneration repair, and the technical effect of improving the matching degree of the functional active substance and the optimal requirements of wound repair is improved through the distribution, the content and the microstructure design of bioactive inorganic substance powder components.

Before explaining the details of the present solution, the concepts to which the present solution may relate are explained first:

bone injury

For the purposes of the present invention, "bone injury" means bone defect, bone loss, bone fracture, etc. in any part of the human or living animal body, and the implant is required to fill the damaged bone tissue to ensure that the damaged part is repaired and restored as before quickly and completely; for purposes of the present invention, factors of bone injury include, but are not limited to: the bone injury caused by external force injury/rolling, falling, and the like, the bone injury caused by explosive shock wave, foreign matter invasion, and the like, the bone injury caused by irregular application or excessive movement, the bone loss caused by skeletal degenerative disease, the bone injury caused by drug abuse, misuse, side effects, and the like, the bone injury caused by bone lesion tissues such as bone tumor, bone infection, bone necrosis, and the like, the bone tissue injury caused by soft tissue lesion or infection involvement, or the bone injury problem artificially caused by the bone tissue close to the lesion required by the operation path (such as treatment of brain tumor).

Biologically active inorganic substance

For the purposes of the present invention, "biologically active inorganic substance" means a completely biodegradable inorganic biomaterial for promoting healing of human bone fractures, bone injury regeneration repair or even healing and reconstruction of adjacent soft tissue injuries, and for achieving bone biomechanical correction, including bioactive ceramics, bioactive glass ceramics, preferably β -wollastonite, α -wollastonite, whitlaite, akermanite, diopside, hydroxyapatite, anhydrous calcium phosphate, dibasic calcium phosphate dihydrate, tetracalcium phosphate, octacalcium phosphate, β -tricalcium phosphate, α -tricalcium phosphate, amorphous calcium phosphate, calcium pyrophosphate, β -dicalcium silicate, γ -dicalcium silicate, tricalcium silicate, strontium metasilicate, strontium silicate, tribasic calcium phosphate, bluish-silica apatite, wollastonite, magnesium phosphate, A ceramic of strontium phosphate, gypsum, or a two-phase/three-phase composite ceramic, or a glass ceramic that has not been fully crystallized; also included are bioactive glasses, preferably CaO-SiO₂Is a basic component and contains MgO, SrO, ZnO, CuO and P₂O₅、B₂O₃、Fe₂O₃、Mn₂O₃、Na₂O、ZrO₂、K₂O and/or Li₂A glassy material of one or more oxides of O; the inorganic substance can be prepared by a wet chemical method, a hydrothermal method, an emulsification method, a melting method or a sol-gel method, the particle morphology, the internal microstructure and the particle size of the inorganic substance are not strictly limited, and the inorganic substance can be bioactive ceramics, bioactive glass or any combination of any two of the bioactive ceramics and the bioactive glass.

Components

For the purposes of the present invention, "component" means at least one bioactive ceramic, bioactive glass-ceramic or bioactive glass of chemically not completely identical, and also at least one bioactive ceramic or bioactive glass-ceramic of chemically identical but differing degrees of crystallinity, the identity of the chemical composition means the type or relative content level of the metal ion, acid ion or oxide, and the relative content level of the chemical composition means that there is a difference of more than 0.01% in mass percent or mole percent; the "component" in the present invention may be a single bioactive inorganic substance or a composite of two or more bioactive inorganic substances.

Biodegradation

For the purpose of the present invention, "biodegradation" means that inorganic nonmetallic biomaterials with excellent biosafety and biocompatibility can be dissolved by interstitial fluid or degraded by cell metabolism in a human body, the biodegradation rate of each component in the materials is strictly limited, the time span of complete degradation can be from one month to three years, and the composition of inorganic ions and acid radical ions released in the degradation process can regulate/promote vascularization efficiency and bone regeneration efficiency, can also inhibit inflammatory reaction or inhibit bacteria and sterilize, and can even mediate soft tissue regeneration and repair of a contact interface with bone tissues.

Core-shell structure

For the purposes of the present invention, a "core-shell structure" is a distribution structure of material components made by wrapping and enveloping an outer layer with an inner layer component, the inner layer being not completely enveloped by the outer layer's enveloping component, by means of a mechanical system in which inner and outer spray heads are nested.

Thickness of

For the purposes of the present invention, "thickness" refers to the largest dimension in cross-section of any core layer, shell layer component within a fiber of core-shell structure.

Functional heterogeneous metal ion or acid radical ion

For the purposes of the present invention, a "functional foreign metal ion or acid ion" is any other metal ion or acid ion having bioactive, anti-inflammatory and/or anti-infective properties than the metal ion or acid ion contained in the compound phase in the specific stoichiometric ratio in the bioactive ceramic, bioactive glass-ceramic.

Pore-forming particles

For the purpose of the present invention, the "pore-forming fine particles" refer to organic or inorganic fine particles that can be decomposed and volatilized in a high-temperature environment of 120 ℃ or higher, and also organic or inorganic fine particles that can be dissolved away by soaking in a specific solution.

Non-complete through micro-hole

For the purposes of the present invention, a "non-completely through-penetrating pore" is a collection of pores that are isolated from each other and completely closed, and the proportion of through-penetrating pores that occur between pores is not strictly limited.

Is substantially free of

For the purposes of the present invention, "substantially free" refers to the mass percentage of a particular component, dopant ion, in the core layer or shell layer of the core-shell structure material, and may also refer to the mole percentage of a particular oxide in the bioactive glass, 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 mass% or 0.0 to 0.01 mole%, including all ranges subsumed therein.

Doping

For the purposes of the present invention, "doped" refers to an inorganic substance formed by partially substituting a specific metal ion or acid ion in a bioceramic or bioglass ceramic with one or more other metal ions or acid ions, without having a physically separate second independent phase.

Exposing

For the purposes of the present invention, "exposed" means that the core inorganic component is not completely encapsulated or enclosed by the shell inorganic component at one or both ends of the core-shell structural fiber, and when the core-shell structural fiber is implanted into a bone injury site, the core inorganic component is degraded simultaneously as the shell inorganic component and releases functional inorganic ions into the tissue environment.

The invention relates to a functional biological active ceramic, biological active glass-ceramic, biological active glass or a mixture which can resist pathogenic bacteria and/or control inflammatory reaction and promote tissue regeneration, and the inorganic biological material with the core-shell structure fiber function is formed by inner and outer wrapping.

Directly fill bone tissue injuries related to orthopedics, traumatology, stomatology, maxillofacial department, plastic surgery, ophthalmology, oncology, brain surgery and the like, and play the roles of long-acting infection prevention and inflammation resistance, and synchronous regeneration, repair and reconstruction of the bone injuries and adjacent soft tissue injuries.

To achieve the object, in a first aspect, embodiments of the present application provide a core-shell structured fiber functional inorganic biomaterial, including: the hollow fiber type shell layer comprises a shell layer inorganic matter component and at least one core layer comprises a core layer inorganic matter component, the core layer is wrapped in the hollow fiber type shell layer, the end part of the at least one core layer inorganic matter component is exposed to the outside relative to the shell layer inorganic matter component, and micropores with the porosity of 3% -75% are respectively formed on the core layer and the shell layer; the porosity and the pore size of the micropores are changed by the following conditions: the relative proportion of pore-forming particles added to the shell inorganic component or the core inorganic component; the mass percentage of the shell layer inorganic matter component or the core layer inorganic matter component in the corresponding liquid or semi-fluid dispersing agent; the highest temperature of high heat treatment and the heat preservation time in the preparation process.

In this embodiment, the core layer inorganic component may be plural, and at least one core layer inorganic component is exposed to the outside at one end or both ends of the core-shell structured fibrous functional inorganic biomaterial. The extent of exposure is not critical. This has the advantage that compared to the problem of difficulty in controlling the particle size of inorganic powder particles by mechanical grinding, the present embodiment can control the degradation rate of the inner core layer by the encapsulation of the core-shell structure material, such as: the greater the degree of exposure of the inorganic component of the core layer, the greater the rate of degradation of that component, all other things being equal. Moreover, because the inorganic component of the core layer of the fiber is exposed outside at least one end part, the inorganic component of the core layer does not need to start to degrade after the inorganic component of the shell layer is degraded during application, and the penetration of micropores in the inorganic component of the shell layer is not depended; in other words, the degradation rate of inorganic components in the nuclear layer is not seriously limited by shielding or shielding of any other components, independent degradation can be realized, and the space vacated after the degradation of the nuclear layer can be rapidly grown by new bones, which is extremely favorable for improving the efficiency of complete regenerative repair of bone injury.

In this embodiment, the cross-sectional morphology of the shell and core inorganic components of the core-shell fibers may be adjusted by changing the nozzle morphology, dynamically adjusting the power level of the extruded slurry, or receiving a carrier, etc. For example, staging the extrusion dynamics of the core layer slurry can cause the fibers of the core layer components to change; for another example, when the core-shell primary structure extruded from the circular nozzle is received by a metal plate, the cross section of the core-shell primary structure is changed from a circular shape to an approximately semicircular core-shell primary structure on the surface of the metal receiving plate due to gravity and incomplete consolidation of the slurry.

In this embodiment, the degree of exposure of the core layer of the core-shell structured fiber may be adjusted by the extrusion thrust level (or volume of slurry extruded per unit time) of the core-shell slurry, or by the timing relationship of extrusion or termination of extrusion of the core-shell slurry, or by the shear of the core-shell preliminary structure before the high-temperature heat treatment.

In this example, the diameter or thickness of each of the core layer inorganic component and the shell layer inorganic component in the core, shell structure fiber is 100-. The diameter or thickness of each layer of inorganic substance component can be adjusted within 100-4500 microns by adjusting the size of the core-shell combined nozzle according to actual needs, so that the core-shell structural fiber provided by the scheme can be used as a new material for regeneration and repair of bone tissue damage of various parts and pathological conditions of human bodies or living animals.

In this embodiment, the porosity of the micropores and the size of the micropores may be adjusted to suit various practical needs. That is, specifically, changing the content of each inorganic component of the core layer and the shell layer can change the porosity and the micropore size so as to adjust the degradation rate of the components; the pore-forming particles are added, and the relative proportion of the pore-forming particles to inorganic matters in the nuclear layer and the shell layer can be controlled to change the porosity and the micropore size so as to adjust the degradation rate of the components; the degradation rate of the components is adjusted by changing the porosity and the micropore size by controlling the heat preservation temperature and the heat preservation time length in the preparation process.

In the scheme, the core layer inorganic matter component and the shell layer inorganic matter component can be selected from different biodegradable bioactive inorganic matters, or the same biodegradable bioactive inorganic matter can be selected as the core layer inorganic matter component and the shell layer inorganic matter component, but the micro-pore size and the micro-pore porosity in the core layer inorganic matter component and the shell layer inorganic matter component are different.

In the scheme, the spacing between the inorganic components of the core layers arranged in parallel can be selected in a close fit mode or a discrete distribution mode with a certain spacing; the distribution and arrangement of the inorganic matter components of the core layer and the inorganic matter components of the shell layer on the cross section of the fiber can be selected from a coaxial arrangement mode and an eccentric arrangement mode; meanwhile, the change rate of the concentration of active ions released by inorganic components in the core layer and the efficiency of complete degradation can be adjusted by adjusting the eccentric arrangement degree of the core and shell components on the cross section.

In one embodiment, the degradation rate of the core-shell structure fiber can be reasonably combined by utilizing the intrinsic degradation property of inorganic components of the core layer and the shell layer, so that the fiber filler can maintain the bracket effect for a longer time in bone injury, and functional active ions can be released according to the adaptive condition to adapt to the requirement that the core-shell structure fiber has ideal biological efficacy. Specifically, different inorganic components which degrade slightly faster and slower are respectively arranged in the core layer and the shell layer of the fiber, the inorganic components in the core layer can be degraded preferentially and provide more space for the growth of new bones, and the slightly slower degradation characteristic of the inorganic components in the shell layer can ensure that the fiber structure is maintained in bone injury for a longer time, thereby providing a scaffold framework for the migration and growth of related cells of regenerated bones to the inside.

In one embodiment, the pore size is anywhere from 100 nm to the diameter or thickness of the core or shell in which the pores are located, preferably from 600 nm to any level of the size of the layer thickness, more preferably from 2 to 550 microns.

In one embodiment, the micropores are formed by non-densifying calcination or sintering of the shell layer inorganic component and the core layer inorganic component at the highest heat treatment temperature; or the micropores are formed after the shell layer inorganic matter component and the core layer inorganic matter component are added with pore-forming particles.

In this embodiment, the conditions for non-densifying calcination or sintering may be such that the maximum heat treatment temperature reaches 580-1450 ℃ for a holding time of 30-360 minutes at the maximum heat treatment temperature, depending on the kind of the selected inorganic substance component. The type of pore-forming particles is not limited, and may be a particulate material that can be decomposed and volatilized during high heat treatment at 150 ℃ or higher, preferably polystyrene particles or polymethyl methacrylate particles, or inorganic or organic particles that are rapidly dissolved during soaking and washing solution treatment to generate micropores, preferably gelatin particles or calcium carbonate particles. The pore-forming particles are not particularly limited in size and form, and the preferred pore-forming particles are spherical, ellipsoidal, or rod-like in form.

In addition to the above-mentioned porosity of the micropores being affected by the mass percentage of the inorganic component in the slurry, the porosity of the micropores can also be adjusted by changing the level of the holding temperature and/or the length of the holding time and/or the selection of the pore-forming particles and/or the mass percentage of the pore-forming particles.

Specifically, the inorganic component gradually softens and binds to densification during heating, and the degree of adhesion between particles can be changed by controlling the heating conditions, thereby adjusting the porosity of micropores.

In addition, the inorganic component is used as the matrix and organic particles are added, so that the porosity and the micropore size of micropores can be adjusted under the condition of not changing the phase structure of the matrix.

In one embodiment, the core layer inorganic substance or the shell layer inorganic substance comprises bioactive ceramics, bioactive glass-ceramics and/or bioactive glass, or non-stoichiometric bioactive ceramics, bioactive glass-ceramics doped with functional heterogeneous metal ions, acid ions; the mole percentage of the heterogeneous metal ions and/or acid radical ions in the core layer inorganic matter/the shell layer inorganic matter is 0.01-35% of the total mole percentage of all metal ions and/or acid radical ions in the core layer inorganic matter/the shell layer inorganic matter.

The heterogeneous metal ions are at least one of magnesium ions, strontium ions, zinc ions, copper ions, iron ions, lithium ions, sodium ions and potassium ions; the acid radical ion is at least one of borate ion, silicate ion, phosphate ion, sulfate ion and carbonate ion.

Specifically, under the same other conditions, the doping of the bioactive inorganic matrix with heterogeneous metal ions or acid radical ions can improve or increase the biological efficacy of the fiber material, such as anti-inflammatory function, anti-infection function, vascular function promotion, bone regeneration function promotion, soft tissue repair or healing promotion, and the like.

It should be noted that the doped acid radical ion needs to be different from the acid radical ion of the inorganic matrix. For example, where the inorganic substrate is a phosphate, the doped foreign acid ion may not be a phosphate ion, but may be a silicate ion, a carbonate, or a borate.

The doped heterogeneous metal ions or/and acid radical ions may be compounds containing doped metal ions or acid radical ions actively added to the reaction system for synthesizing the inorganic matrix powder, or the heterogeneous metal ions or/and acid radical ions brought by chemical raw materials required for synthesizing the powder are not completely removed. For example, the inorganic substance matrix is magnesium and sodium co-doped wollastonite ceramic powder, the doped magnesium ions are realized by adding magnesium nitrate into the reaction solution, the doped sodium ions can be introduced from sodium silicate (inorganic salt containing silicate radical required for wollastonite synthesis) during synthesis, and the sodium ions are not actively and completely cleaned and removed, so that the calcined wollastonite ceramic powder contains two heterogeneous metal ions of magnesium and sodium.

In one embodiment, the core layers are juxtaposed within the shell layers, or a portion of the core layers are arranged from the inside out and juxtaposed with at least one core layer within the shell layers, or all of the core layers are included from the inside out within the shell layers.

In this embodiment, a plurality of core layers of inorganic substances are nested or juxtaposed within the shell layers. Taking the core-shell inorganic substance layer-by-layer nesting as an example, the section of the core-shell structure fiber can expose all the core layer components, so that the core layer part of the sheared core-shell structure fiber is not shielded and shielded by other core layers or shell layer components during application and can be independently degraded. Similarly, the structure of the core layer inorganic substances arranged side by side can achieve the effect of independent degradation after shearing. The advantages of this are: through the microstructure design of exposing the core layer outside, the core-shell structure fiber can independently release various functional inorganic ions, thereby having better effects of preventing infection, controlling inflammation and promoting regeneration and repair of bone injury.

In this embodiment, the core layer is formed by sintering at least one core layer inorganic component without densification to form micropores, or at least one core layer inorganic component is formed by adding pore-forming particles to form micropores; the shell layer is obtained by solidifying the shell layer inorganic matter component after forming micropores without densification sintering, or is obtained by adding pore-forming particles to the shell layer inorganic matter component to form micropores; the micropores in the core layer and the shell layer are the sum of micropores formed by uncompacted sintering and micropores formed by pore-forming particles.

Specifically, the core layer is formed by adding micropores with the porosity of 3% -75% formed on at least one inorganic component of the core layer into a core layer spray head and pushing out the micropores; the obtained inorganic substance component of the core layer is provided with micropores, so that the contact area of the degradable bioactive inorganic substance component in the core layer and the outside is increased, and the degradation rate is improved. The scheme controls the degradation speed of the fiber material by adjusting the porosity of the nuclear layer, and compared with the prior art, the dosage of the released metal ions and acid radical ions can be properly adjusted so as to better match the regeneration and repair speed of new bone tissues.

Similarly, the shell layer is formed by adding micropores with the porosity of 3% -75% formed on the inorganic matter component of the shell layer into a shell layer spray head and pushing out the micropores. The obtained inorganic component of the shell layer is provided with micropores, and the dosages of metal ions and acid radical ions released by the inorganic components of the shell layer and the core layer can be controlled by adjusting the porosity of the micropores in the inorganic component of the shell layer.

It is further noted that the core inorganic component and the shell inorganic component are selected from different biodegradable, biologically active inorganic materials.

In this embodiment, the core/shell inorganic components are each selected from at least one bioactive inorganic substance in order to avoid various drug abuse or resistance problems and to prevent inflammatory reactions and infection risks after bone injury is filled with the core-shell structure fibers, by utilizing the anti-infective and inflammation-controlling properties of the bioactive inorganic substance independent of conventional drugs.

In this example, each core inorganic component is different from the bioactive inorganic material selected for the shell inorganic component, i.e., each core inorganic material and shell inorganic material are selected for different components in the bioactive inorganic material, respectively, such that the resulting material is prepared to have a core-shell structure.

In one embodiment, the bioactive ceramic, bioactive glass ceramic is preferably a fully or partially crystalline substance of a silicate, phosphate, borate, sulfate of calcium, magnesium, zinc, strontium, and may also be a composite or eutectic of two to more inorganic substances of silicates, phosphates, borates, sulfates; the bioactive glass is made of CaO-SiO₂Is a basic component and contains MgO, SrO, ZnO, CuO and P₂O₅、B₂O₃、Fe₂O₃、Mn₂O₃、Na₂O、ZrO₂、K₂O and/or Li₂Glassy substance composed of one or more oxides of O, CaO and SiO₂The mole percentages of the oxides are respectively 12-46% and 24-78%, and the sum of the mole percentages of other oxides in the glass is 8-64%, except CuO, ZnO and Fe₂O₃、Mn₂O₃、Li₂The total content of O in mol percent does not exceed 12 percent, and the relative mol percent content and proportion of the rest oxides are not strictly limited. If CuO, ZnO or Fe is used₂O₃、Mn₂O₃、Li₂The total O mole percent content in excess of 12% may be cytotoxic or otherwise of no value, and thus the content of the oxides in the total O mole percent content of 12% is not limited.

In one embodiment, the heterogeneous metal ions are at least one of magnesium ions, strontium ions, zinc ions, copper ions, iron ions, lithium ions, sodium ions, and potassium ions; the acid radical ion is at least one of borate ion, silicate ion, phosphate ion, sulfate ion and carbonate ion; the mole percentage of the heterogeneous metal ions and/or acid radical ions doped in the bioactive ceramics and the bioactive glass-ceramics is 0.01 to 35 percent of the total mole percentage of all the metal ions and/or acid radical ions in the bioactive ceramics and the bioactive glass-ceramics. More preferably from 0.01% to 20%, most preferably from 0.2% to 15%.

In one embodiment, the inorganic material doped with heterogeneous metal ions or acid radical ions is obtained by mixing heterogeneous metal ions or acid radical ions of one or more of magnesium, strontium, zinc, copper, iron, boron, lithium, silicon, phosphorus, sodium and potassium with beta-wollastonite, alpha-wollastonite, whitish wollastonite, akermanite, diopside, hydroxyapatite, anhydrous calcium phosphate, dibasic calcium phosphate dihydrate, tetracalcium phosphate, octacalcium phosphate, beta-tricalcium phosphate, alpha-tricalcium phosphate, amorphous calcium phosphate, calcium pyrophosphate, beta-dicalcium silicate, gamma-dicalcium silicate, tricalcium silicate, strontium metasilicate, strontium silicate, di-n-orthophosphate, bluish-silica apatite, magnesium silicate, magnesium phosphate, strontium phosphate and gypsum.

In one embodiment, the core/shell inorganic component is selected from biodegradable inorganic materials, and the time period for complete in vivo degradation of the core/shell inorganic component is from 1 month to 3 years.

In this embodiment, the time period of complete degradation can be adjusted to any time period within the interval of 1 month to 3 years by changing the diameter or thickness of the layer in which the specific component is located, the mass percentage content of the powder of the component in the slurry of the mixture with the liquid or semi-fluid dispersant, the doping rate of the heterogeneous metal ions and acid radical ions in the component, or the microporous structure, and the like.

In one embodiment, the shell inorganic component of the core-shell fibrous functional inorganic biomaterial is in the form of continuous fibers and the core inorganic component of the core-shell fibrous functional inorganic biomaterial is in the form of continuous fibers, discrete fibers, or discrete particles.

Specifically, the form of any one of the core layers inside the shell layer is not limited, and may be continuous fibers formed by providing a stable extrusion thrust such that the slurry continuously and independently passes through the nozzle, or discrete fibers or discrete particles formed by intermittently adjusting the extrusion thrust of the core layer slurry.

In a second aspect, the present application provides a method for preparing a core-shell structure fiber functional inorganic biomaterial, comprising the following steps:

respectively adding powder of a core layer inorganic substance/shell layer inorganic substance component into a liquid or semi-fluid dispersing agent, stirring to form slurry, wherein the mass percentage of the core layer inorganic substance/shell layer inorganic substance component in the slurry is 10% -75%, then adding pore-forming particles into the slurry according to 0.01% -135% of the mass of the powder, continuously stirring uniformly, respectively adding each slurry into a corresponding core-shell combined spray head to form a core-shell primary structure body, receiving by using a receiving carrier, and separating the core-shell primary structure body from the receiving carrier;

soaking and/or washing the core-shell primary structure, then drying, shearing the dried core-shell primary structure, and then performing high-heat treatment, wherein the high-heat treatment comprises the following steps: the temperature rising rate from the normal temperature to the highest temperature is 1-6 ℃/min, the highest temperature is 580-1450 ℃, the heat preservation time at the highest temperature is 30-360 min, and the inorganic biomaterial with the core-shell structure fiber function is obtained by natural cooling.

In the first step, different bioactive inorganic components can be ground into powder, the particle size of the powder is not strictly limited, and the invention is in the scope of the invention as long as uniform slurry can be formed in the liquid or semi-fluid dispersing agent and can be smoothly pushed out of the nozzles of the core and shell nozzles to form fibrous materials.

The liquid or semi-fluid dispersant may be a liquid or semi-fluid material that does not undergo a rapid dissolution reaction with the core/shell inorganics and is capable of complete decomposition and volatilization during heat treatment. The liquid or semi-fluid dispersant can be selected from water solution containing organic molecules, or liquid prepared by dispersing or dissolving organic molecules in ethanol, isopropanol, glycerol, and liquid polyethylene glycol, wherein the organic molecules are preferably algal polysaccharides, chitosan, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, polycarbonate, hyaluronic acid, or polyethylene glycol polymer.

The mass percentage of the organic molecules in the liquid or semi-fluid substance is preferably 0.2%, 0.5%, 1.0%, 3.0%, 5.0%, 10.0%, 20.0%.

The mass percentage of the inorganic powder in the slurry is preferably 35%, 45%, 55%, or 65%.

In the preparation process, the cross section size level of each bioactive inorganic substance component in the cross section of the core-shell structure fiber functional inorganic biological material subjected to high-heat treatment can be changed by changing the mass percentage of the bioactive inorganic substance component in the slurry and the concentration of organic molecules or dynamically adjusting the thrust of the slurry from a nozzle of a spray head.

In addition, in the invention, the pore-forming method for forming micropores in each layer of bioactive inorganic substance component is not strictly limited, and besides the easily soluble or volatile pore-forming agent, a foaming agent can be added into the slurry to form tiny pores, and a micropore network is formed after high-heat treatment.

The pore-forming fine particles are preferably contained in an amount of 1%, 10%, 15%, 30%, 40%, 50%, 75%, 100%, 120% by mass of the core layer inorganic substance/shell layer inorganic substance component powder.

In the preparation process of the invention, the micropore density, the connectivity among micropores, the degradation rate of inorganic components of each layer and the ion release dosage level of the inorganic components of each layer in the fiber body in the core-shell structure fiber functional inorganic biomaterial can be adjusted by changing the relative content of the added pore-forming particles.

In the first step, the receiving carrier or the solid, liquid and gas environment used for ejecting the fibers from the nozzle is not strictly limited, and may be an inorganic or organic solution, a hot air atmosphere, or various heating flat or curved carriers.

For example, the receiving carrier is a liquid containing organic molecules or a liquid containing inorganic salts or a drying apparatus. The receiving carrier solution preferably contains an aqueous solution of chitosan, acid gelatin, calcium nitrate, calcium acetate or calcium chloride, and the mass concentration of the organic compound or inorganic salt contained in the receiving carrier solution is 0.05% to 20%.

In the preparation process, the shape, the outer diameter and the continuity of the core layer components are not strictly limited, the core layer components and the shell layer components can be continuous fibers with uniform fiber outer diameters, the core layer components can also be fibers with periodically changed outer diameters similar to cowpea segmental fibers, and the core layer components can be continuous fibers, segmental fibers or non-completely wrapped shell layers of cowpea-like particles. The rate of degradation of a particular mineral component can be adjusted by varying the diameter or thickness of the layer in which the mineral component is located, the content of the mineral component.

In the preparation process of the invention, the length of the inorganic biomaterial with the core-shell structure fiber function is not strictly limited, the fiber length can be adjusted by the duration from the start to the termination of the power maintenance of the extruded slurry, or by the shearing of the core-shell primary structure before the high heat treatment, or by the secondary shearing of the core-shell structure fiber after the high heat treatment, and the fiber is cut into any length at the maximum scale level in any bone injury, which falls into the scope of the invention.

In the preparation process, the length/diameter ratio of the core-shell structure fiber function inorganic biomaterial is not strictly limited, fiber-based porous materials with different dimensions, which can be constructed by the core-shell structure fiber function inorganic biomaterial obtained after high-heat treatment through treatment such as shearing, stacking, assembling and the like, are in the scope of the invention, the post-treatment of the core-shell structure fiber function inorganic biomaterial after high-heat treatment is not strictly limited, and the fiber is cut into sheets, short rods and even ultra-long fibers with the length/diameter ratio between the length and the outer diameter of a shell layer of 0.3 or more.

In the preparation process of the invention, the types of the doped heterogeneous metal ions and acid radical ions, or CaO-SiO₂The amorphous glass with basic composition contains other oxides, can regulate infection and inflammation prevention and control of fiber, promote vascularization efficiency, osteogenic regeneration repair efficiency or soft tissue wound healing repair efficiency, and can regulate anti-infection, anti-inflammation and other performance levels.

In the second step, the temperature system of the heat treatment is not strictly limited, and the crystallization degree of the bioactive inorganic substance in the fiber and the scale level of the sintered micropores can be controlled by adjusting the heating rate, the heat preservation temperature and the heat preservation time.

The maximum temperature is preferably 650 ℃, 700 ℃, 750 ℃, 780 ℃, 900 ℃, 1080 ℃, 1150 ℃, 1180 ℃, 1220 ℃, 1240 ℃, 1280 ℃, 1350 ℃ or the like.

The length of the heat-retention time is preferably 1 hour, 2 hours, 3 hours, etc.

For the purpose of the present invention, the nozzle hole shape of the core layer or shell layer nozzle head is not particularly limited, and is preferably circular, elliptical, square, rectangular or hexagonal.

The number of the nuclear layer nozzles is not strictly limited, and the nuclear layer nozzles can be a coaxial nuclear-shell structure combination formed by one or more nuclear layer nozzles and one shell layer nozzle, or a nuclear-shell structure combination formed by two or more nuclear layer nozzles arranged side by side and one shell layer nozzle, or a core-shell structure combination formed by a plurality of nuclear layer nozzles nested inside and outside and then arranged side by side with other nuclear layer nozzles and one shell layer nozzle.

The inner diameter length of the core layer nozzle of the core-shell combined nozzle is 100-3000 microns, and the inner diameter length of the shell layer nozzle is 300-4500 microns.

The inner diameter of the shell layer nozzle is 130-600% of the outer diameter of the nuclear layer nozzle.

In one embodiment, the different microstructures of the prepared multiple core-shell structure fiber functional inorganic biomaterials comprise bioactive ceramics, bioactive glass-ceramics, bioactive glasses or mixtures with the same phase, which are different in micropore size and micropore density; or the bioactive ceramics, bioactive glass-ceramics, bioactive glass or mixtures of different phases are the same in micropore size and micropore density; or the content level of the heterogeneous metal ions or acid radical ions doped by the bioactive ceramics, bioactive glass-ceramics, bioactive glass or the mixture of the same phase is different; or the thickness and content level of the inorganic matter component of the core layer and the inorganic matter component of the shell layer are different.

In one embodiment, the inorganic biomaterial with the core-shell structure fiber function after high heat treatment can be further subjected to post-treatment by adopting a specific solution, so that specific core layer components in the fiber are selectively and rapidly dissolved, and the core-shell structure fiber is converted into a hollow porous core-shell structure fiber, and the invention also belongs to the field of the invention.

The embodiment brings the following advantages: the core-shell structure fiber functional inorganic biomaterial with various forms can be obtained by adjusting the components of the inorganic biomaterial, the content of heterogeneous metal ions or acid radical ions, the thickness of a core layer/shell layer, the micropore size, the micropore density and the like, so that the requirements of regeneration and repair of new bone tissues under different bone injury indications are met.

The method provided by the second aspect of the invention can be used for preparing the core-shell structure fiber functional inorganic biomaterial.

In a third aspect, the embodiments of the present application provide an application of the core-shell structure fiber functional inorganic biomaterial, wherein the core-shell structure fiber functional inorganic biomaterial according to any one of the first aspect is applied to control inflammation, prevent infection, promote bone regeneration and complete repair; wherein, the bone injury cavity is filled with core-shell structure fiber, and a pore canal formed by degrading the core-shell structure fiber is grown by the new bone tissue; the matching degree between the degradation of the core-shell structure fiber and the inflammation control, the infection control and the regeneration and repair of new bone tissues is regulated and controlled by controlling the micropore size and micropore density of each component in the core-shell structure fiber and/or the components and thickness of each component and/or the content of heterogeneous metal ions or acid radical ions doped in each component.

The main contributions and innovation points of the embodiment of the application are as follows:

1) chemically, silicates, phosphates, borates, sulfates, etc. of calcium, magnesium, zinc, strontium, etc. and some CaO-SiO₂The amorphous glass with basic composition has excellent biological safety and biocompatibility, and functional metal ions or acid radical ions necessary for human metabolism are doped into inorganic matters in advance or oxides thereof are integrated into the amorphous glass, so that the amorphous glass is favorable for regulating the degradation rate of the inorganic matters and releasing functional ion compositions, and further the fiber material for promoting the regeneration and repair of the damaged hard tissues of the human body is constructed.

2) In terms of microscopic and macroscopic structures and forms, substances with excellent biocompatibility are distributed according to a core-shell structure to be wrapped inside and outside the components, and micro-pores are constructed inside specific components, so that the degradation rate of each component and the dosage level of an inorganic ion composition are greatly favorably adjusted, particularly, the cross sections of two ends of the fiber are exposed out of some core layer components through shearing, stacking, assembling and the like, the early degradation of all the components is not influenced by the adverse effect of any other components caused by wrapping, the micro-pores formed by the early degradation of inorganic components of the specific core layer are ensured to be grown by new bone tissues, and the matching degree and the repairing efficiency between the fiber degradation and the tissue regeneration and repair can be favorably adjusted.

3) In the biological effect, the bioactive inorganic substances with different physicochemical properties, biological activity, biological degradation characteristics and biological functions are organically integrated, the structural stability, the degradation rate and the dynamic dosage of ion release of the material can be accurately regulated and controlled, and further the synchronization problems of series problems of tissue regeneration, infection resistance, inflammation resistance and the like in soft and hard tissue (synergistic) repair can be solved, and the repair of certain challenging bone tissue wounds in clinic can be favorably broken through.

4) In terms of operability, the inorganic biological material with the fiber form of the core-shell structure can be directly filled according to the size of a wound space, and can also be used for carrying out treatment such as cutting, stacking or assembling on fibers, filling fine and irregular wounds or large bone injury cavities and being beneficial to being paved in thin skull wounds.

Therefore, compared with the conventional inorganic microsphere particles, three-dimensional printing supports, organic hydrogel, organic sponge, organic-inorganic composite materials and the like, the new material for bone tissue wound regeneration and repair, which can solve various parts of a human body and pathological conditions, has more outstanding advantages in the aspect of solving the scope of clinical human body musculoskeletal tissue injury indications, and the fiber composite biological inorganic material with the core-shell structure is extremely favorable for being directly covered, filled or used for bone tissue regeneration and repair after being simply processed.

Based on the core-shell structure fiber functional inorganic biomaterial, the core-shell structure fiber functional inorganic biomaterial can be applied to bone tissue trauma related to orthopedics, stomatology, maxillofacial surgery, plastic surgery, brain surgery and the like, bone tissue necrosis (such as diabetic foot) affected by soft tissue lesion trauma and regenerative repair medicine of adjacent soft tissue trauma.

The details of one or more embodiments of the application are set forth in the accompanying drawings and the description below to provide a more thorough understanding of the application.

Drawings

The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the application and together with the description serve to explain the application and not to limit the application. In the drawings:

fig. 1 is a cross-sectional appearance view or a fiber sidewall appearance view of a sample cut into different lengths after being dried and cut into fibers, wherein the fibers are shot by a digital camera.

Fig. 2 is appearance images of the zinc-sodium-doped β -calcium silicate @ silicon-strontium-doped β -tricalcium phosphate fibers taken by a digital camera before (left three) and after (right three) calcination.

Fig. 3 is a cross-sectional view of the composite bioactive ceramic fiber with the coaxial core-shell structure, which is scanned by a scanning electron microscope and doped with the zinc-sodium doped β -calcium silicate @ silicon-strontium doped β -tricalcium phosphate, before calcination (a) and after calcination (B).

Fig. 4 is an appearance morphology diagram (a) and a cross-section microstructure diagram (B) of the core-shell structure fiber composite material, which is photographed by a digital camera and has the core layer doped with strontium-zinc-doped akermanite and the phosphorus-doped breccinite and the shell layer doped with silicon-doped α -tricalcium phosphate.

Fig. 5 is an appearance and morphology diagram of a core-shell structure type composite bioceramic fiber biomaterial, which is shot by a digital camera and has a structure that a core layer is a short fiber, and the core layer is a continuous shell layer doped with silicon-strontium-doped β -tricalcium phosphate and a core layer doped with zinc-magnesium-doped β -calcium silicate.

Fig. 6 is an appearance and appearance diagram of the core-shell structure type composite bioceramic fiber biomaterial, which is obtained by shooting with a digital camera that the silicon-strontium-doped β -tricalcium phosphate shell layer completely wraps the zinc-magnesium-doped β -calcium silicate core layer.

FIG. 7 is a sectional view of a nozzle of a core-shell structure, wherein the inner diameter parameters of the nozzle are as follows:

a: the inner diameters of the core and shell layer spray heads are respectively

And

a combination of (1);

b: the inner diameters of the inner core, the middle core and the outer shell layer are respectively

And

a combination of (1);

c: the ellipse length and the ellipse minor diameter of the nuclear layer spray head and the diameter of the shell layer spray head are respectively 2800 mu m, 1800 mu m and

a combination of (1);

d: the side lengths of the core-shell nozzles are respectively the combination of 600 mu m and 1000 mu m;

e: the inner diameters of the inner core and the outer shell spray head are respectively

And

a combination of (1);

f: the side lengths of the inner core and outer shell nozzles are a combination of 300 μm and 1000 μm, respectively.

Detailed Description

The technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention; it is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments that can be derived by one of ordinary skill in the art from the embodiments given herein are intended to be within the scope of the present invention.

It is understood that the terms "a" and "an" should be interpreted as meaning that a number of one element or element is one in one embodiment, while a number of other elements is one in another embodiment, and the terms "a" and "an" should not be interpreted as limiting the number.

The "@" represents that the material is in a core-shell structure, and the components on the left side and the right side of the @ represent the components of a core layer and a shell layer respectively; in the case of multiple @ juxtapositions, the right component of the rightmost @ represents the shell component, the left component of the leftmost @ represents the innermost core layer component, and the components between the leftmost and rightmost @ represent the other core layer components between the innermost core layer and the shell. The "-" between the two components means that the two components belong to the juxtaposed core layers.

The diameter is represented by the number of points,

the right hand number is the scale level of the diameter. Long side (axis) and short side (axis) long connector with x being rectangle or ellipse.

The following description of the embodiments of the present invention is provided by way of specific examples, and other advantages and effects of the present invention will be readily apparent to those skilled in the art from the disclosure herein. It is to be understood that the scope of the invention is not to be limited to the specific embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. The test methods in the following examples, in which specific conditions are not specified, are generally carried out according to conventional methods or according to conditions recommended by the respective manufacturers.

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

All amounts are in terms of mass percent or molar mass percent of the final core-shell structured fibrous biomaterial, unless otherwise specified.

It should be noted that any particular upper limit value can be associated with any particular lower limit value within any range of the stated value.

In the examples, the foreign metal ions, acid ions or oxides and the content levels thereof not specifically described in the bioactive ceramic and bioactive glass powder used do not mean that the raw material powder does not contain functional foreign metal ions or acid ions, and there is no specific description that the content levels of foreign metal ions and acid ions are insufficient to cause sufficient biological functions.

Example 1 [ porous bioactive ceramic fiber with co-doped core and shell ceramics ]: the biological active ceramic fiber with the coaxial core-shell structure is doped with the zinc-sodium, the beta-calcium silicate, the silicon-strontium and the beta-tricalcium phosphate.

1) 2.2% of calcium and 4.6% of phosphorus were doped with strontium-silicon-substituted strontium-phosphorus-doped β -tricalcium phosphate powder and 2.8% of calcium and silicon-substituted strontium-phosphorus-doped β -tricalcium phosphate powder, respectively45g of zinc-and 1.8-sodium-doped beta-calcium silicate powder are respectively dispersed into 75mL of 1.5-percent sodium alginate aqueous solution, stirred to form two paste slurries, and 14 g of polymethyl methacrylate microspheres with the diameter of 5-8 μm and 24 g of polystyrene microspheres with the diameter of 40-70 μm are respectively added into the two slurries. Placing the two liquid storage containers into two storage containers respectively connected with inner and outer double-layer coaxial tubular nozzles, wherein the inner diameters of nozzle openings of the coaxial core-shell structure nozzles are 700 and 1600 μm, synchronously injecting the slurry in the two storage containers into the nozzle openings of the nozzles to form core-shell structure paste fibers, and adopting 15% Ca (NO)₃)₂The solution receives the fiber, the collected proper amount of fiber is soaked in the receiving solution for 60 minutes, then the fiber is taken out and respectively dried for 18 hours at 45 ℃ and 80 ℃ for standby;

2) and cutting the dried fiber into short fibers with the lengths of 0.6-10 mm, and calcining the short fibers at 1150 ℃ for 120 minutes to obtain the coaxial core-shell structure composite bioactive ceramic fiber composite biomaterial with the shell layer doped with silicon-strontium and the core layer doped with zinc-sodium and beta-calcium silicate.

Respectively passing the two slurries, namely the slurry containing the pore-forming microspheres and the slurry containing the zinc-sodium doped beta-calcium silicate and the slurry containing the silicon-strontium doped beta-tricalcium phosphate, through single-nozzle nozzles with inner diameters of 700 and 1600 μm according to the process conditions in the steps 1) and 2), and calcining the obtained single-component fiber at 1150 ℃ for the same time under the same conditions. Tests show that the micropore porosities of the micropores in the two monocomponent ceramic fibers doped with the zinc-sodium-doped β -calcium silicate and the silicon-strontium-doped β -tricalcium phosphate are 22.9% and 38.7%, respectively, which indicates that the porosity of the core layer and the shell layer in the coaxial core-shell structure composite bioactive ceramic fibers doped with the zinc-sodium-doped β -calcium silicate and the silicon-strontium-doped β -tricalcium phosphate in the embodiment is respectively about 23% and 39%.

FIG. 1 is a pattern of short fibers with core-shell structure, which can be cut into different lengths, after drying in the above preparation process.

FIG. 2 is an appearance of the fiber before calcination (left three strips) and after calcination (right three strips), showing that the fiber diameter is shrunk by the sintering process.

FIG. 3 is SEM photographs of cross sections of fibers before and after calcination, and it can be seen that large-scale pore-forming microspheres are distributed in a shell layer region, large-scale microporous pore channels are reserved after sintering, and the distribution characteristics of the fibers in a core-shell layer structure on a microstructure can be seen.

Example 2 [ three-layer core-shell structure porous bioactive ceramic composite fiber ]: the coaxial core-shell structure composite bioactive ceramic fiber is formed by doping akermanite with zinc, strontium, beta-tricalcium phosphate and magnesium, and beta-calcium silicate.

1) Dispersing 48g of zinc-doped akermanite with 3.1% of calcium being replaced by zinc, strontium-doped beta-tricalcium phosphate with 4.7% of calcium being replaced by strontium and magnesium-doped beta-calcium silicate powder with 8.3% of calcium being replaced by magnesium into 75mL of sodium alginate-carboxymethyl cellulose aqueous solution with the concentration of 1.2% and 0.05%, respectively, stirring to form three paste slurries, and adding 15 g of polystyrene microspheres with the diameter of 10-12 micrometers, 18 g of polystyrene microspheres with the diameter of 5-6 micrometers and 12 g of polystyrene microspheres with the diameter of 50-65 micrometers into the three slurries respectively. Then the materials are respectively placed into three material storage containers connected with inner, middle and outer layers of coaxial tubular nozzles, and the inner diameters of nozzle openings of the coaxial core-shell structure nozzles are respectively 400 micrometers, 900 micrometers and 1600 micrometers. And then the slurry in the three liquid storage containers is synchronously injected into the nozzle opening of the spray head to form core-shell structure paste fiber, and 20 percent of Ca (CH) is adopted₃COO₃)₂The solution receives the injected continuous fiber, proper amount of fiber is collected in the receiving solution and then is continuously soaked for 30 minutes, and then the fiber is taken out and is respectively dried for 12 hours at 60 ℃ and 90 ℃ for standby;

2) and cutting the dried fiber into short fibers with the lengths of 1.5-4 mm, and calcining the short fibers at 1080 ℃ for 120 minutes to obtain the core-shell structure fiber inorganic bioactive composite material with the zinc-doped akermanite, the strontium-doped beta-calcium phosphate and the magnesium-doped beta-calcium silicate as an inner core layer, an intermediate core layer and an outer shell layer respectively.

According to the process conditions of the steps 1) and 2), respectively enabling the slurry containing the pore-forming microspheres, namely the zinc-doped akermanite, the strontium-doped beta-tricalcium phosphate and the magnesium-doped beta-calcium silicate to pass through single-port nozzles with nozzle openings of 400 mu m, 900 mu m and 1600 mu m, and carrying out calcination treatment on the obtained single-component fiber at 1080 ℃ for the same time under the same conditions. According to tests, the porosity of micropores in the three single-component ceramic fibers, namely the zinc-doped akermanite, the strontium-doped beta-tricalcium phosphate and the magnesium-doped beta-calcium silicate, is 24.7%, 27.7% and 20.1%, respectively. Therefore, in the coaxial core-shell structure composite bioactive ceramic fiber doped with akermanite and strontium doped with β -tricalcium phosphate and magnesium doped with β -calcium silicate in the embodiment, the porosity of the inner core layer, the porosity of the intermediate core layer and the porosity of the outer shell layer are respectively at different levels of-25%, 28%, 20%, and the like.

Example 3 [ core-shell structured composite bioactive ceramic fiber with juxtaposed core layers ]: the strontium-zinc-doped akermanite and the phosphorus-doped bredigite are respectively a core layer and a shell layer, and the shell layer is made of the bioactive ceramic fiber composite material.

1) 35g of each of 3.4% and 2.8% of powder of strontium/zinc doped akermanite doped with strontium and zinc respectively, 8% of phosphorus doped whitlaite doped with silicon and phosphorus, and 6% of powder of α -tricalcium phosphate doped with silicon and phosphorus respectively was dispersed in 75mL of an aqueous sodium alginate solution having a concentration of 2.4%, and stirred to form three kinds of paste slurries, and 14 g of polystyrene microspheres having a diameter of 5 μm were added to each of the three kinds of pastes. And then the water-saving type core-layer spray heads are respectively placed into three storage containers which are respectively connected with a parallel dual-core-layer spray head and an outer shell-layer spray head, the inner diameters of nozzle openings of the parallel core-layer spray heads are 900 micrometers and 900 micrometers respectively, and the long diameters and the short diameters of elliptical nozzles of the shell-layer spray heads are 2600 micrometers and 2000 micrometers respectively. And synchronously injecting the slurry in the three liquid storage containers into a nozzle opening of a spray head to form core-shell structure paste fibers, and adopting 25% of CaCl₂The solution receives the fiber, the collected proper amount of fiber is soaked in the receiving solution for 60 minutes, then the fiber is taken out and respectively dried for 8 hours at 45 ℃ and 100 ℃ for standby;

2) and cutting the dried fiber into short fibers with the lengths of 0.7-4 mm, and calcining the short fibers at 1280 ℃ for 120 minutes to obtain the parallel core-shell structure fiber composite biomaterial, wherein the parallel core-shell structure fiber composite biomaterial comprises 5% of strontium-substituted calcium/zinc-doped akermanite, 4% of zinc-substituted calcium-substituted strontium/zinc-doped akermanite, 8% of phosphorus-substituted phosphorus-doped bredigonite and 6% of silicon-substituted silicon-doped alpha-tricalcium phosphate as shell components.

Respectively subjecting the ceramic powder slurry containing the strontium-zinc-doped akermanite, the phosphorus-doped whitlaite and the silicon-doped alpha-tricalcium phosphate containing the pore-forming microspheres to calcination treatment at 1280 ℃ for the same time through a single-port spray head with the inner diameters of 900 and 900 micrometers or a single-port spray head with the elliptical nozzle openings of 2600 and 2000 micrometers according to the process conditions of the steps 1) and 2). According to tests, the microporous porosities of the single-component ceramic fibers doped with akermanite, celosite and α -tricalcium phosphate respectively are 28.7%, 26.2% and 25.9%. This indicates that in the bioactive ceramic fiber material doped with strontium-zinc-doped akermanite-phosphorus-doped bredigonite @ silicon-doped α -tricalcium phosphate, the micropore porosities in the two parallel core layers and the shell are at levels of about 29%, about 26%, and the like, respectively.

Fig. 4 is a morphology diagram and a cross-sectional structure diagram of a core-shell structure fiber composite material with a core layer doped with strontium-zinc picroside and phosphorus doped xonotlite and a shell layer doped with silicon-doped α -tricalcium phosphate, which show that a core-shell structure composite bioceramic fiber with two core layer components arranged in parallel can be wrapped in one shell layer component.

Example 4 [ core-shell structural fiber material of bioactive ceramic and bioactive glass-ceramic composite ]: copper-doped beta-calcium silicate @24CaO-56SiO₂-6SrO-5MgO-9Na₂O coaxial core-shell structure bioactive fiber material.

1) 36 g of copper-doped β -calcium silicate ceramic powder with 1.2% of calcium being substituted by copper, and bioactive glass 24CaO-56SiO₂-6SrO-5MgO-9Na₂Dispersing 34 g of O powder into 100mL and 75mL of sodium alginate-sodium carboxymethylcellulose aqueous solution with the concentration of 1.5 percent and 0.2 percent respectively, stirring to form two pasty slurries, and then adding 32 g of polymethyl methacrylate microspheres with the diameter of 5-7 mu m and polyphenyl with the diameter of 100 mu m into the two slurries of the bioactive ceramic and the bioactive glass respectivelyEthylene microspheres 3.5 g. Then the core-shell structure spray head is respectively placed into two storage containers which are respectively connected with an inner layer coaxial tubular spray head and an outer layer coaxial tubular spray head, and the inner diameters of nozzle openings of the core-shell structure spray heads are 2400 mu m and 4500 mu m respectively. And then synchronously injecting the slurry in the two liquid storage containers into the nozzle opening of the spray head to form core-shell structure paste fiber, and adopting 12% Ca (NO)₃)₂Wetting the flat plate by the aqueous solution to receive fibers, soaking the collected proper amount of fibers in 1.5 percent chitosan solution for 60 minutes, taking out the fibers, and respectively drying the fibers at 45 ℃ and 90 ℃ for 12 hours for later use;

2) shearing the dried fibers into short fibers with the length of 2-10 mm, and calcining the short fibers at 850 ℃ for 120 minutes to obtain a copper-doped beta-calcium silicate ceramic nuclear layer and 24CaO-56SiO₂-6SrO-5MgO-9Na₂The bioactive glass-ceramic fiber biomaterial is compounded by a coaxial core-shell structure with O bioactive glass-ceramic as a shell layer.

Respectively mixing the copper-doped beta-calcium silicate ceramic powder containing the pore-forming microspheres and 24CaO-56SiO according to the process conditions in the steps 1) and 2)₂-6SrO-5MgO-9Na₂The obtained single-component fiber is calcined for the same time at 850 ℃ by O bioglass powder slurry through a single-port spray head with the inner diameter of 2400 and 4500 mu m. Tests show that the bioactive glass is converted into glass-ceramic containing glass and ceramic phases through high-temperature treatment, and the micropore porosities in the copper-doped beta-calcium silicate bioactive ceramic and the bioactive glass-ceramic fiber are 47.1% and 8.8% respectively, so that the micropore porosities in the core layer and the shell layer are respectively 47% and 9% of the same level in the core-shell structure bioactive ceramic @ bioactive glass-ceramic composite fiber material in the embodiment.

Example 5 [ different heterogeneous metal ions doped core-shell structure bioceramic fibers of the same ceramic respectively ]: the magnesium-doped beta-calcium silicate and the zinc-doped beta-calcium silicate are doped with the biological active fiber material with the coaxial core-shell structure.

Similar to example 4, in step 1), the bioactive glass 24CaO-56SiO was replaced by zinc-doped β -calcium silicate powder with 4.8% of calcium being replaced by zinc₂-6SrO-5MgO-9Na₂O，The preparation method comprises the steps of substituting 3.6% of copper-doped beta-calcium silicate powder with magnesium-substituted magnesium-doped beta-calcium silicate powder, substituting 1.2% of copper-substituted calcium with copper, adding 47 g of polymethyl methacrylate microspheres with the diameter of 8-12 microns into core layer slurry, and adding no pore-forming particles into shell layer slurry; in step 2, the dried fiber was calcined at 1160 ℃ for 180 minutes. Other steps and conditions are the same as those in steps 1) and 2) of example 4, so that the coaxial core-shell structure composite bioceramic fiber biomaterial with the core layer made of magnesium-doped β -calcium silicate of 3.6% and the shell layer made of zinc-doped β -calcium silicate of 4.8% can be obtained.

According to the process conditions of the steps 1) and 2), respectively passing the two bio-ceramic powder slurries of the magnesium-doped beta-calcium silicate and the zinc-doped beta-calcium silicate through single-nozzle nozzles with inner diameters of 2400 and 4500 μm, and calcining the obtained monocomponent fiber at 1150 ℃ for the same time. Tests prove that the micropore porosities of the two single-component biological ceramic fibers of the magnesium-doped beta-calcium silicate and the zinc-doped beta-calcium silicate are 72.6% and 3.2%, which shows that the porosity of the magnesium-doped wollastonite ceramic fiber can be remarkably improved by a high-proportion pore-forming agent, and the sintering compactness of the wollastonite ceramic fiber can be remarkably improved by zinc doping, so that the micropore porosities of the core layer and the shell layer of the coaxial core-shell structure biological active fiber material of the magnesium-doped beta-calcium silicate and the zinc-doped beta-calcium silicate in the embodiment are 73% to 3% respectively.

Example 6 [ core-shell structure bioactive ceramic fibers of different micropore porosities ]: the magnesium-doped beta-calcium silicate @ magnesium-doped beta-calcium silicate coaxial core-shell structure bioactive fiber material.

According to the similar steps of example 5, in step 1), 3.6% of magnesium-doped β -calcium silicate powder with calcium being replaced by magnesium-substituted calcium is used for replacing 4.8% of zinc-substituted zinc-doped β -calcium silicate powder, and other procedures and conditions are the same as example 5, so that the core-shell structure ceramic fiber with different micropore porosities and magnesium doping rates in the core layer and the shell layer can be obtained, namely, the 3.6% magnesium-doped β -calcium silicate is the coaxial core-shell structure composite bioceramic fiber biomaterial of the core layer and the shell layer respectively, and the porosity of the core layer and the shell layer is respectively about 74% and about 3.5% through tests.

Example 7 [ core-shell structure bioactive ceramic fibers with different ion doping rates ]: 3.6% magnesium doped beta-calcium silicate @ 6.8% magnesium doped beta-calcium silicate.

According to the similar steps of the embodiment 6, in the step 1), the ceramic powder in the core-shell ceramic slurry and the ceramic powder in the shell-shell ceramic slurry are respectively 3.6% magnesium-doped beta-calcium silicate and 6.8% magnesium-doped beta-calcium silicate, 12 g of polymethyl methacrylate microspheres with the diameter of 8-10 μm are added, and the core-shell structure bioactive ceramic fibers with the different magnesium doping rates and the microporous porosity of 11-10% in the core and the shell can be obtained by the same procedures and conditions as the embodiment 6.

Example 8 [ core-shell structured bioactive ceramic composite fiber with discontinuous fiber or particle in core layer ]: the zinc-magnesium is doped with the beta-calcium silicate @ silicon-strontium and the beta-tricalcium phosphate coaxial core-shell structure bioactive fiber material.

Similar to the process of example 1, in step 1), the extrusion of the core layer component is delayed by 400 ms compared with that of the shell layer component at the beginning of the slurry injection, and is suspended for 400 ms every 400 ms or 1200 ms, and other processes and conditions are the same as those of steps 1) and 2) of example 1, so as to obtain the core-shell structure type composite bioceramic fiber biomaterial with the continuous shell layer doped with silicon-strontium and the beta-tricalcium phosphate doped with zinc-magnesium.

Fig. 5 is an appearance and morphology diagram of the prepared core-shell structure type composite bioceramic fiber biomaterial with the core-shell structure type short fiber, wherein the core layer is doped with silicon-strontium-doped β -tricalcium phosphate and the core layer is doped with zinc-magnesium-doped β -calcium silicate.

Example 9 [ control group: core-shell structure bioactive ceramic composite fiber with a shell layer completely wrapping a core layer: the zinc-magnesium is doped with the beta-calcium silicate @ silicon-strontium and the beta-tricalcium phosphate coaxial core-shell structure bioactive fiber material.

According to the similar steps of example 8, in step 1), when the slurry starts to be injected, the extrusion of the core layer component is delayed by 200 milliseconds compared with that of the shell layer component, and the extrusion is suspended every 600 milliseconds, and the extrusion of the shell layer component is also stopped after the delay of the suspension of the core layer component is delayed by 200 milliseconds, the initial core-shell structure body after drying is not cut, and other steps and conditions are the same as those of steps 1) and 2) of example 8), so that the core-shell structure type composite bioceramic fiber biomaterial with the silicon-strontium-doped β -tricalcium phosphate shell layer, which is wrapped by the zinc-magnesium-doped β -calcium silicate core layer, can be obtained.

Fig. 6 is an appearance and morphology diagram of the core-shell structure type composite bioceramic fiber biomaterial, in which the silicon-strontium-doped β -tricalcium phosphate outer shell layer completely wraps the zinc-magnesium-doped β -calcium silicate core layer, prepared as described above.

Examples 10 to 33：

The difference from example 1 is that the powder raw materials (phase, whether to dope heterogeneous metal ions) in steps 1) and 2), the shape and inner diameter parameters of the nozzle opening of the core-shell structure nozzle, and certain preparation conditions and parameters (the highest temperature and the heat preservation time of high heat treatment) are performed according to the following table, the heterogeneous metal ion doping refers to partial substitution of the heterogeneous metal ions for calcium ions in stoichiometric ratio ceramics or partial substitution of silicon and phosphorus, and the nozzle of the nozzle is a circular hole or a square hole, so that various different coaxial core-shell structure bioactive fiber biomaterials can be obtained.

Example 34：

The core-shell structure fiber composite biomaterials prepared in example 1, example 2, example 3, and example 9 were used for bone injury regeneration repair test.

The method comprises the following specific steps: the method comprises the steps of carrying out high-pressure steam sterilization on microsphere particle samples, equally dividing 60 healthy male New Zealand white rabbits (with the weight of 3.4 +/-0.1 kg) with the age of 26 weeks into 5 groups, carrying out whole body sterilization, using bone drills to make defects with the diameter of 6.5mm and the depth of 7.2mm at the position 2.0cm away from the joint head of the femoral neck of the hind leg along the backbone direction, cutting the back layer and the muscle layer of the same animal, respectively establishing a bone injury model and a muscle embedding model, respectively filling the first three groups with fibers (the length/diameter ratio is 0.7-1.8) prepared in examples 1, 2, 3 and 9, respectively filling the fifth group with no filling material, namely a blank control group, then carrying out tissue suture, and injecting intravenous antibiotics. After the animals were subjected to X-ray examination in vivo at 3 rd, 8 th and 14 th weeks after the rearing under standard conditions, the animals were photographed in a gross manner to observe the defect-repairing effect.

The results show that: the blank control group has extremely low bone injury repair efficiency, and the bone repair rate is less than 25% after 14 weeks. Meanwhile, in the group of short fiber materials of examples 1, 2 and 3: after 3 weeks, new bone development and rich vascularization occur in the fiber-packed porous network, and the regeneration rate of the new bone reaches 22-29 percent; after 8 weeks, the regeneration rate of three groups of new bones reaches 44% -53%, and the nuclear layers at the two ends of the short fiber are rapidly degraded, and bone tissues grow into the fiber; after 14 weeks, the fiber degradation rate in the bone injury of the three groups of examples reaches 66-75%, and the bone regeneration rate reaches more than 61-78%. However, in the model of filling example 9, at 14 weeks after the material implantation, the fiber degradation rate in the bone injury is 44% -50%, and the bone regeneration rate is 43% -47% or more, indicating that the core layer is completely wrapped by the shell layer and then degraded slowly, the release of osteogenic active ions is also slow, and the osteogenic efficiency and material degradation in the defect are significantly lower than those in the bone injury repair cases of the other examples.

Similarly, in the short fiber muscle embedding model: the inflammation of muscle tissues is obviously reduced at 3 weeks, and abundant new blood vessels are formed in a fiber network; after 8 weeks, the fibers are obviously degraded, and a new tissue similar to a connective tissue is formed in the fiber network; all the fibers of the fiber groups of examples 1-3 were significantly degraded at 14 weeks, and the formed new connective tissue was similar to the neighboring tissue, indicating that tissue remodeling had occurred and muscle damage had been repaired; the fiber of example 9 degraded more slowly than the first three materials. However, in all of the above animal models, it was observed that the short fiber material produced inflammatory response control in both bone injury and muscle, and no infection occurred without continuous antibiotic intervention. This example shows that the core layer of the core-shell structure fiber functional biomaterial is moderately exposed, and the components of the core and shell layers are endowed with a porous structure, so that the fiber functional biomaterial has excellent anti-infection capability and also has excellent effects of improving vascularization and bone regeneration efficiency in defects and the like.

It should be understood by those skilled in the art that various features of the above embodiments can be combined arbitrarily, and for the sake of brevity, all possible combinations of the features in the above embodiments are not described, but should be considered as within the scope of the present disclosure as long as there is no contradiction between the combinations of the features.

The above examples merely represent several embodiments of the present application, and the description thereof is more specific and detailed, but should not be construed as limiting the scope of the present application. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the concept of the present application, which falls within the scope of protection of the present application. Therefore, the protection scope of the present application shall be subject to the appended claims.

Claims

1. A core-shell structured fibrous functional inorganic biomaterial, comprising: the fiber shell layer is composed of a shell layer inorganic matter component, and at least one core layer is composed of a core layer inorganic matter component, the core layer is wrapped in the shell layer, the end part of at least one core layer is exposed relative to the shell layer, micropores with the porosity of 3% -75% are respectively formed in the core layer inorganic matter component and the shell layer inorganic matter component, and the porosity and the size of the micropores are changed through the following conditions:

the relative proportion of pore-forming particles added to the shell inorganic component or the core inorganic component;

the mass percentage of the shell layer inorganic matter component or the core layer inorganic matter component in the corresponding liquid or semi-fluid dispersing agent;

the highest temperature of high heat treatment in the preparation process and the heat preservation time.

2. The core-shell structured fiber-functional inorganic biomaterial of claim 1, wherein the micropores are formed by non-densification calcination or sintering of the shell layer inorganic component and the core layer inorganic component at a maximum heat treatment temperature, or are formed after addition of pore-forming particles.

3. The core-shell structured fiber-functional inorganic biomaterial of claim 1, wherein the core-shell inorganic component or the shell inorganic component comprises a bioactive ceramic, a bioactive glass-ceramic and/or a bioactive glass, or a non-stoichiometric bioactive ceramic, a bioactive glass-ceramic doped with functional heterogeneous metal ions, acid ions; the mole percentage of the heterogeneous metal ions and/or acid radical ions in the core layer inorganic matter component/the shell layer inorganic matter component is 0.01-35% of the total mole percentage of all metal ions and/or acid radical ions in the core layer inorganic matter component/the shell layer inorganic matter component.

4. The core-shell structured fiber functional inorganic biomaterial of claim 3, wherein the heterogeneous metal ions are at least one of magnesium ions, strontium ions, zinc ions, copper ions, iron ions, lithium ions, sodium ions, potassium ions; the acid radical ion is at least one of borate ion, silicate ion, phosphate ion, sulfate ion and carbonate ion.

5. The core-shell structural fiber functional inorganic biomaterial of claim 1, wherein the core layer is juxtaposed within the shell layer, or a portion of the core layer is arranged from inside to outside and juxtaposed with at least one core layer within the shell layer, or all of the core layer is encapsulated within the shell layer from inside to outside.

6. The core-shell structured fibrous functional inorganic biomaterial of claim 1,

the highest temperature of high heat treatment is 580-.

7. The core-shell structured fiber-functional inorganic biomaterial of claim 1, wherein the length of complete in vivo degradation of the core-shell inorganic component and the shell inorganic component is 1 month to 3 years.

8. The core-shell fiber-functional inorganic biomaterial of claim 1, wherein the shell inorganic component of the core-shell fiber-functional inorganic biomaterial is in the form of continuous fibers, and each of the core inorganic components of the core-shell fiber-functional inorganic biomaterial is in the form of continuous fibers, discrete fibers, and/or discrete particles.

9. A preparation method of a core-shell structure fiber functional inorganic biomaterial is characterized by comprising the following steps:

respectively adding core layer inorganic matter component/shell layer inorganic matter component powder into a liquid or semi-fluid dispersing agent, stirring to form slurry, adding pore-forming particles into the slurry according to the mass percentage of the core layer inorganic matter component/shell layer inorganic matter component powder of 10-75% in the slurry, continuously stirring uniformly, respectively adding each slurry into corresponding core-shell combined nozzles to form a core-shell primary structure, receiving the core-shell primary structure by using a receiving carrier, and separating the core-shell primary structure from the receiving carrier;

soaking and/or washing the core-shell primary structure, drying, shearing the dried core-shell primary structure into any length with the length/diameter ratio between the length and the outer diameter of the primary structure not less than 0.3, and then performing high-heat treatment,

wherein the high heat treatment comprises the following steps: the heating rate from the normal temperature to the highest temperature is 1-6 ℃/min, the highest temperature is 580-1450 ℃, the heat preservation time at the highest temperature is 30-360 min, and then the inorganic biomaterial with the core-shell structure fiber function is obtained after natural cooling.

10. The method for preparing a fiber-functional inorganic biomaterial having a core-shell structure according to claim 9, wherein the liquid or semi-fluid dispersant substance is a substance that does not undergo a rapid dissolution reaction with the core layer inorganic substance/shell layer inorganic substance and can be completely decomposed and volatilized during a high heat treatment.

11. The application of the inorganic biomaterial with the core-shell structure fiber function is characterized in that the inorganic biomaterial with the core-shell structure fiber function according to any one of claims 1 to 8 is applied to bone injury and the inflammation control, infection prevention and treatment of the damaged soft tissue close to the bone injury, and the tissue regeneration and complete repair of the bone injury part are promoted; wherein, the bone injury is filled with core-shell structure fiber, pore channels between the core-shell structure fiber and micropores formed by degrading the bioactive inorganic components of the core and the shell layer in the fiber are rapidly grown by the new bone tissue; by controlling the pore size, pore density and/or the pore size in each mineral component in the core-shell structured fiber

Composition, thickness and/or of each component

The content of the heterogeneous metal ions or acid radical ions doped in each component

Regulating and controlling the matching degree of the degradation of the fiber with the core-shell structure, the control of inflammation, the prevention and the treatment of infection and the regeneration and the repair of new bone tissues.