TW202337504A - Biological glass fiber for regenerative medical materials and applications therefrom - Google Patents

Abstract

The present invention provides a biological glass fiber for regenerative medical materials, comprising a biological glass or a biologically-inert glass made of a glass chemical composition. The glass chemical composition comprises in weight percentage, 5 to 25 wt% Na ₂O, 45 to 67 wt% SiO ₂, 15 to 25 wt% CaO, 2 to 6 wt% P ₂O ₅, 1 to 8 wt% MgO, 8 to 12.5 wt% K ₂O, 0.1 to 5 wt% total combined of non-toxic elements found in Group 5 and non-toxic elements found in Transition Metal Groups 3B, 4B and 5B, based on 100 wt% of the glass chemical composition; wherein the biological glass fiber forms a fiber configuration. The biological glass fiber is a soluble, resorbable, light transmittable and controllable absorption time regenerative material, and the biological glass fiber can mediate: therapeutic lymphangiogenesis, stem cell regeneration, bone cell regeneration and neurovascular regeneration, or it can be used as a cell carrier.

Description

Bioglass fiber for regenerative medical materials and its application

The present invention relates to a biological glass fiber used in regenerative medical materials and its application, particularly to a stem cell that is absorbable, can conduct light, can control the absorption time, induce the new formation of lymphatic vessels, and guide stem cells to directional arrangement and proliferation. Bioglass fiber used in regenerative medical materials and its application as a carrier for regeneration, bone cell regeneration, neurovascular regeneration or cells.

Regenerative medicine refers to the production of functional and vital body organs and tissues to repair or replace unhealthy organs and tissues in the body caused by aging, disease, and damage. The field of regenerative medicine therefore holds the promise of transforming damaged tissues and organs by stimulating the body's own repair mechanisms to heal previously irreparable tissues or organs.

In 1969, Dr. Lawrence Hench developed a simple glass composed of four glass chemical components, which was used as a bone substitute material for animals and could also be used in the human body. Dr. Lawrence Hench added additional ingredients to this basic glass chemistry, and researchers working with this family of materials coined the name "Bioglass"; the material is now known as biocompatible glass. A material classified as "bioactive glass".

In recent years, human tissues and organs have been harvested in laboratories for transplantation into patients. Alternative approaches include releasing drugs within the body to stimulate direct regeneration of the patient's tissue. New regenerative medicine technologies are rapidly developing in the areas of bone, cartilage, skin, bladder, ureter, kidney, liver and neuroscience. Second, since cells are extremely sensitive to the physicochemical properties of the culture environment, it is important to carefully select regenerative materials. The mechanical properties and pore structure of the materials used need to be considered as these will affect tissue repair and growth after implantation. The regenerative material can differentiate into adipocytes, chondrocytes, nerve cells, osteoblasts or muscle cells, depending on culture conditions or the addition of specific growth factors.

In view of the existing technology in this field, the inventor of the present invention has made an innovative breakthrough, overcomes the shortcomings of traditional delivery methods of living medical materials, and improves the actual chemical efficacy of regenerated materials. This invention takes a new approach, leveraging technology developed for lighting and communications fiber manufacturing, to bring vastly improved regenerated medical materials to market, boosting industry growth and improving society's health.

The main purpose of the present invention is to provide a bioglass fiber for regenerative medical materials, fiber structure and application thereof. The single bare fiber structure or mixed fiber structure formed by the glass chemical composition of the present invention can generate a cell activity mechanism, create an appropriate environment for cells in the body, and induce the new integration of the immune system. Secondly, the bioglass fiber has precise structural dimensions and a unique formula ratio to achieve manufacturing capabilities that can adjust the dissolution and absorption rate. Furthermore, the biological glass fiber can also be used as a medical material to induce the neogenesis of lymphatic vessels, induce the directional arrangement and proliferation of stem cells, and has the potential to form skeletons and nerve conduits. In addition, bones and nerve blood vessels can be formed by modifying and improving the glass chemical composition or fiber structure of the present invention.

In order to achieve the above object, the present invention provides a bioglass fiber for regenerative medical materials, including a bioactive glass composed of a glass chemical composition and a bioinert glass. The glass chemical composition of the bioactive glass includes : 5~25wt% sodium oxide, 45~67wt% silica, 15~25wt% calcium oxide and 2~6wt% phosphorus pentoxide; calculated based on the total weight percentage of 100wt% of the glass chemical composition; Among them, the glass chemical composition consists of a single bare fiber structure and a mixed fiber structure.

In the bioglass fiber for regenerated medical materials of the present invention, the glass chemical composition of the bioglass further includes 1 to 8 wt% magnesium oxide and 8 to 12.5 wt% potassium oxide.

In the bioglass fiber for regenerative medical materials of the present invention, the glass chemical composition of the bioinert glass includes 0.1 to 5 wt% of transition metal elements of the 5A group and 3B, 4B and 5B.

The present invention applies a manufacturing method modified from the well-known bioglass fiber manufacturing technology used in communication and lighting technology to form bioglass into a single bare fiber structure or a mixed fiber structure. These bioglass fibers can be solid or microscopic tubes in nature. Additionally, individual fibers can be aggregated and combined to form more complex fiber-based structures.

In the bioglass fiber for regenerative medical materials of the present invention, the single bare fiber structure is composed of the bioactive glass or the bioinert glass.

In the bioglass fiber for regenerative medical materials of the present invention, in addition to a single bare fiber structure made of bioactive glass or bioinert glass, the mixed fiber structure may also include: (1) a core made of bioactive glass and A single coated fiber made of an outer layer coated with bio-inert glass, (2) a single bare fiber microtube made of bio-active glass or bio-inert glass, (3) a microtube with a coating made of bio-active glass or bio-inert glass. A single mixed fiber structure made of multiple fused internal microtubules, (4) Multiple single bare fibers made of bioglass or bioinert glass in an unfused bundle structure with interstitial voids including natural bioglass capillaries, (5) Multiple single bare fiber microtubules in an unfused bundle structure with interstitial voids including additional natural biological microtubules, and (6) Multiple single coated fibers in an unfused structure with interstitial voids including biological Extra natural microtubes of inert glass.

In the bioglass fiber for regenerative medical materials of the present invention, the hybrid fiber structure further includes a single-hole microtube fiber structure composed of the bioactive glass or the bioinert glass.

In the bioglass fiber for regenerative medical materials of the present invention, the hybrid fiber structure further includes a hybrid solid fiber structure composed of two or more layers of the bioactive glass, the bioinert glass, or a combination thereof.

In the bioglass fiber for regenerative medical materials of the present invention, the hybrid fiber structure further includes a hybrid single-hole microtube fiber structure composed of two or more layers of the bioactive glass, the bioinert glass, or a combination thereof. .

In the bioglass fiber for regenerative medical materials of the present invention, the hybrid fiber structure further includes a hybrid porous microtubular fiber structure composed of the bioactive glass or the bioinert glass.

In the bioglass fiber for regenerative medical materials of the present invention, the hybrid porous microtubular fiber structure is composed of two or more layers of the bioactive glass or the bioinert glass, and has a circular shape or a non-circular shape. Cross-section geometry.

In the bioglass fiber for regenerative medical materials of the present invention, the single bare fiber structure and the hybrid fiber structure include an X-ray opaque bioinert glass fiber. Additionally, the glass chemical composition can contain specific bioadditive materials to introduce X-ray opacity into one or more bioglass fibers to create new structures depending on the type of application. Additionally, the glass chemistry can contain specific bioinert additive materials to introduce X-ray opacity into one or more bioglass fibers to create new structures, depending on the type of application.

In the bioglass fiber for regenerative medical materials of the present invention, based on the modification of the glass chemical composition or the fiber component diameter size parameters, the single bare fiber structure and the mixed structure fiber structure have different properties in human or animal organisms. of recycled material absorption time.

In the bioglass fiber for regenerative medical materials of the present invention, the single bare fiber structure has a diameter of 3~25 μm.

In the bioglass fiber for regenerative medical materials of the present invention, the hybrid porous microtubular fiber structure has a circular diameter of 3 to 35 μm.

In the bioglass fiber for regenerative medical materials of the present invention, the pore diameter of the hybrid porous microtubular fiber structure with a non-circular cross-sectional geometry is between 3 and 125 μm.

To achieve another object of the present invention, the present invention provides an application of bio-glass fiber for regenerative medical materials. The bio-glass fiber is composed of a glass chemical composition as described in item 1 of the patent application scope. The bio-glass Applications of fibers include inducing therapeutic lymphangiogenesis, inducing directional arrangement and proliferation of stem cells, stem cell regeneration, inducing bone cell regeneration, inducing neurovascular regeneration, or serving as cell carriers.

In the application of the bioglass fiber for regenerative medical materials of the present invention, the bioglass fiber activates macrophage-derived lymphatic endothelial cell progenitor cells and promotes lymphatic vessel regeneration and aqueous humor drainage through therapeutic lymphangiogenesis. without fibrosis.

In the application of the bio-glass fiber for regenerative medical materials of the present invention, during the clinically effective time, the bio-glass fiber is co-cultured with dental pulp stem cells (DPSCs), and within 15 to 18 hours, the dental pulp stem cells tend to Bioglass fiber growth, within 22 to 25 hours on bioglass fiber grows and forms odontoblasts that form dentin within days. Generally speaking, stem cells are defined as undifferentiated cells with the ability of self-renewal and multi-lineage differentiation. In addition to odontoblasts that form dentin, DPSCs can also differentiate into mesodermal and non-mesodermal tissue cells, including: osteoblasts, adipocytes, chondrocytes, myocytes, neurons and endothelial cells, melanocytes, Hepatocytes and retinal stem cells.

The following describes the implementation of the present invention through specific examples. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. In addition, the present invention can also be implemented or applied through other different specific embodiments, and various modifications and changes can be made without departing from the spirit of the present invention.

"Bioglass fiber", "bioinert glass fiber", "bioactive glass fiber", "X-ray opaque bioactive glass fiber", or "X-ray opaque" appear throughout the specification of the present invention. "Bio" in nouns such as "bio-inert glass fiber" means biological materials that can be applied to an organism, "active" means biological materials that can be absorbed by the organism, and "inert" means that they are not absorbed by the organism. Biological materials absorbed by living organisms.

Example 1

Please refer to Figures 1 to 2F. Figure 1 is a schematic diagram of a single bare fiber structure of the present invention; Figure 2A is a schematic diagram of a hybrid fiber structure of the present invention; Figure 2B is an SEM image of the hybrid solid fiber structure sample 1 of the present invention. Image; Figure 2C is an SEM image of the hybrid solid fiber structure sample 2 of the present invention; Figure 2D is an SEM image of the hybrid solid fiber structure sample 3 of the present invention; Figure 2E is an SEM image of the hybrid solid fiber structure sample 4 of the present invention Image; and Figure 2F is an SEM image of the hybrid solid fiber structure sample 5 of the present invention.

Preferred embodiment 1

As shown in Figures 1 to 2F, the present invention provides a bioglass fiber for regenerative medical materials including: a bioactive glass composed of a glass chemical composition and a bioinert glass. The glass chemical composition includes: 21.5wt% sodium oxide, 48.0wt% silica, 24.5wt% calcium oxide and 6wt% phosphorus pentoxide, calculated based on the total weight percentage of 100wt% of the glass chemical composition; wherein, the glass chemical composition The material forms a single bare fiber structure and a mixed fiber structure. The regeneration chemical absorption time (hereinafter referred to as "absorption time"), that is, the time required for the regeneration glass material to integrate with biological tissue, depends on the specific chemical composition of the glass.

As shown in Figure 1, the single bare fiber structure 1 is formed by known melt drawing and micromachining techniques. As shown in Figure 2A, the hybrid fiber structure 2 with more than one layer is also formed by melt drawing and micro-machining technology. In other words, the hybrid fiber structure 2 can be composed of two or more layers of bioglass materials, and the absorption time of each layer of the hybrid fiber structure 2 can be determined according to different application types.

Alternatively, as shown in Figures 2B to 5C, multiple bioglass compositions are added to a single bioglass fiber. The shape of the bioglass fibers can be varied, and the absorption time of each bioglass fiber can be varied to suit the type of application. Furthermore, the hybrid fiber structure 2 is a basic building block and is combined and fused based on the application type to form a hybrid solid fiber structure 20, or a hybrid solid fiber structure 20a, or a hybrid single hole microtubular fiber structure 21, or a hybrid Porous microtubular fiber structure 22. In addition, the single bare fiber structure 1 has a diameter between 3 and 25 μm; the hybrid solid fiber structure 20 and the hybrid solid fiber structure 20a have a diameter between 3 and 35 μm; and the hybrid single-hole microtube fiber structure 21 and The hybrid porous microtubular fiber structures 22 each have a pore diameter between 3 and 125 μm.

The biological glass fiber formed by the glass chemical composition of the biological glass fiber used in regenerative medical materials of the present invention can be used for therapeutic lymphangiogenesis, inducing stem cell directional arrangement and proliferation, inducing stem cell regeneration, inducing bone cell regeneration, and inducing neurovascular regeneration. or as cell carriers.

The regenerated medical glass material of the present invention is different from traditional medical polymer materials, which rely on degradation and dissociation into tiny sharp particles before slow metabolism. The medical glass material of the present invention dissolves quickly and completely like sugar in water. In addition, the regenerative medical material of the present invention can be safely and effectively absorbed by the human body. The regenerative medical materials used in the present invention will not have foreign matter retained in the body, and there will be no phenomenon of biological tissue coating due to foreign matter retention. Patients do not experience the discomfort of sequelae (a pathological complication) caused by the treatment, and if necessary, the original implant site can be re-treated indefinitely.

Preferred embodiment 2

The bioglass composition for regenerative medical materials includes: 6.5wt% sodium oxide, 50wt% silica, 20wt% calcium oxide, 6wt% phosphorus pentoxide, 6.5wt% magnesium oxide and 11wt% % of potassium oxide, calculated based on 100wt% of the total weight of the composition; wherein, the bioglass fiber composition forms the single bare fiber structure 1 or the mixed fiber structure 2 through known melt drawing and micro-processing techniques.

Furthermore, the hybrid fiber structure 2 is a basic building block and is combined and fused based on the application type to form the hybrid solid fiber structure 20, or the hybrid solid fiber structure 20a, or the hybrid single hole microtubular fiber structure 21, or hybrid Porous microtubular fiber structure 22. In addition, the single bare fiber structure 1 has a diameter between 3 and 25 μm; the hybrid solid fiber structure 20 and the hybrid solid fiber structure 20a have a diameter between 3 and 35 μm; and the hybrid single-hole microtube fiber structure 21 and the hybrid solid fiber structure 20a have a diameter between 3 and 35 μm; The hybrid porous microtubular fiber structures 22 each have a pore size between 3 and 125 μm.

The biological glass fiber formed by the glass chemical composition of the biological glass fiber used in regenerative medical materials of the present invention can be used for therapeutic lymphangiogenesis, inducing stem cell directional arrangement and proliferation, inducing stem cell regeneration, inducing bone cell regeneration, and inducing neurovascular regeneration. or as cell carriers.

As shown in FIGS. 2B to 2F , the hybrid solid fiber structure 20 includes at least one of the bioactive glass fiber 201 , the bioinert glass fiber 202 , an X-ray opaque bio-inert glass fiber 203 or an X-ray opaque fiber. Bioactive glass fiber 204. Consistent with existing bioglass fiber manufacturing technology, multiple bioglasses are surrounded by glasses with different refractive indices, softening temperatures, and expansion coefficients, such that the circumferential surfaces surrounding the multiple bioglasses are coated and fused to form the hybrid solid fiber structure 20 . The mixed solid fiber structure 20 can induce bone cell regeneration, bone tissue osseointegration, and osteoblast integration.

As shown in Figures 2B to 2F, the outer layer of the hybrid solid fiber structure 20 is composed of the bio-inert glass fiber 202, which is acid and alkali resistant and an insoluble material. The bioinert glass fiber 202 contains trace elements from the transition groups of the periodic table of elements and non-toxic elements from Group 5. Transition elements include the lanthanides of Group 3B, and the elements of Groups 4B and 5B. As shown in Figure 2B, the outer layer of the hybrid solid fiber structure 20 is composed of bioinert glass fibers 202; the center of the hybrid solid fiber structure 20 is composed of bioactive glass fibers 201, which has good light transmittance; and in the hybrid solid fiber structure 20, the outer layer is composed of bioactive glass fibers 201. Between the outer layer and the center of the fiber structure 20 is a layer of x-ray opaque bio-inert glass fiber 203 .

In Figure 2C, there are three sector-shaped bioactive glass fiber 201 members in the hybrid solid fiber structure 20, and the remainder are X-ray opaque bio-inert glass fibers 203, which contain bio-inert X-ray opaque additives. And can be observed with an X-ray camera. In Figure 2D, there are 5 bioactive glass fibers 201 in the hybrid solid fiber structure 20. In Figure 2E, there are 7 bioactive glass fibers 201 in the hybrid solid fiber structure 20. The hybrid solid fiber structure 20 is absorbed to form grooves that can be used for osseointegration; the remainder is the X-ray opaque bio-inert glass fiber 203, which is X-ray opaque and can be observed with an X-ray camera.

As shown in FIGS. 2B to 2E , the hybrid solid fiber structure 20 is composed of the bioactive glass fiber 201 , the bioinert glass fiber 202 and the X-ray opaque bioinert glass fiber 203 , all of which have different dissolution times. . As shown in Figure 2F, the hybrid solid fiber structure 20a is the same as the hybrid solid fiber structure 20 of Figure 2F, but the hybrid solid fiber structure 20a of Figure 2F is composed of X-ray opaque bioactive glass fibers 204. As shown in Figure 2F, the biological glass fiber 201a is composed of chemical components with an enhanced dissolution rate and can be absorbed by the living body in about 2 to 7 days; the bioactive glass fiber 204 with X-ray opacity can be absorbed in about 30 days. Bioabsorbable; the bioactive glass fiber 201 can be absorbed by the organism in about 65 days.

The bioglass fiber 201 induces therapeutic lymphangiogenesis. The purpose of the hybrid solid fiber structure 20 which is radio-opaque is to facilitate radiography by identifying the location of the bioactive glass fiber 201 implanted in the organism. In addition, the hybrid solid fiber structure 20 in Figures 2B, 2C and 2D may also be composed of bioglass fibers with different dissolution rates based on the type of application.

As can be seen from Table 1 below, for all other comparable conditions (temperature, pH, liquid medium, fiber diameter, etc.), higher SiO ₂ (silica) content results in lower dissolution rates and thus regeneration The material absorption time is long, and the diameter of the biological materials in Table 1 is 15 μm.

Table 1 Sodium oxide (wt%) Silicon dioxide (wt%) Calcium oxide (wt%) Phosphorus pentoxide (wt%) Dissolution time (unit: approximately days) Experiment 1 18~25 45 25 2~6 7 Experiment 2 18~24 50 twenty three 2~5 30 Experiment 3 5~15 60 20 2~4 65

Please refer to FIGS. 3A and 3B . FIG. 3A is an SEM image of the single-hole microtube fiber structure 23 with a hybrid core 222 having a square geometry of the present invention. Figure 3B is an SEM image of the single hole microtubular fiber structure 23 of the hybrid core 222 with an elliptical geometry of the present invention.

Please refer to FIG. 4A to FIG. 4B. FIG. 4A is an SEM image of the hybrid single-hole microtube fiber structure 21 of the present invention. Figure 4A demonstrates the present invention's broad hybrid construction flexibility for applying different types of bio- and bio-inert glass materials in successive layers. Figure 4B is an SEM image of the 2-layer hybrid single-hole microtube fiber structure of the present invention.

Figure 5A is a photomicrograph image of the tip of the hybrid porous microtubule fiber structure of the present invention.

Figure 5B contains an SEM image of an example of a conceivable cross-section for a hybrid porous microtubular fiber structure of the present invention and demonstrates the broad flexibility of the hybrid construct fabrication method. Any example can be used as a drug carrier and chemical drugs can be carried in microtubules. During treatment, the chemicals the patient needs are placed in microscopic tubes and the mixed fibers are placed inside the human or animal body. When the chemical reaches the site to be treated, the chemical is released to the treatment site. Furthermore, the number, shape, and size of the holes of the microtubules can be easily changed to suit the drug release rate according to the needs of use. In addition, as shown in the figure, the holes of the microtubes may be circular or polygonal, and the present invention is not limited thereto.

5C is an SEM image of an example of a cross-section of a hybrid porous microtubule fiber structure of the present invention; wherein the hybrid porous microtubule fiber structure 22 as the primary outer cladding has multiple layers made of microtubule fibers 221 Fused microtubules.

Lymphatic regeneration test

experimental animals

The 8-week-old male New Zealand white rabbits used in the experiment weighed approximately 2000~2500g. All experimental animals were kept in individually air-conditioned animal rooms with room temperature maintained at 22 ^° C and relative humidity maintained at 45%, and water and feed were adequately supplied. The animals were given a period of at least 4 weeks to acclimate before experiments. The breeding environment, handling and all experimental procedures of experimental animals are in compliance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH).

The area around the eyes of a New Zealand white rabbit was shaved and then disinfected with iodine and 70% alcohol. Then, a 26- or 27-gauge needle with a fiber bundle built into the single bare fiber structure or the mixed fiber structure implant was used. Scleral puncture into the anterior chamber. Keep the position of the single bare fiber structure or the mixed fiber structure implant unchanged, and at the same time retract and withdraw the 26- or 27-gauge needle to leave the fiber bundle implant and complete the surgical operation. Please refer to Figure 6. Figure 6 is a histopathological section image of the bioactive glass fiber and new lymphatic vessels used in the regenerative medical material of the present invention. As shown in Figure 6, the red arrow indicates the new lymphatic tissue along the fistula tract. The location of the tube, this bioactive glass fiber activates macrophage-derived lymphatic endothelial cell progenitor cells and promotes lymphatic regeneration and aqueous humor drainage through therapeutic lymphangiogenesis without fibrosis, lymphatic stent placement into the eye Drainage begins and is completely absorbed after three months. Lymphangiogenesis (Lymphangiogenesis) The immune system grows lymphatic vessels. After 7 months, the structure produced by the lymphatic vessels diffuses from thick tubes to become thinner and naturally balances the drainage pressure. After 7 months Lymphatic vessels still drain smoothly.

The back of the New Zealand white rabbit was shaved, and then disinfected with iodine and 70% alcohol. A small opening was made on the back of the New Zealand white rabbit using a scalpel, and the bioactive glass fibers were separated. Implanted subcutaneously in New Zealand white rabbits.

Table 2 below shows the hybrid fiber structure implanted under the skin of rabbits, and the lymphangiogenesis of the hybrid fiber structure with different diameters was observed after 12 weeks.

Table 2 Diameter (μm) Implantation status after 12 weeks Experiment a 2 Mild inflammation and bleeding Experiment b 5 Mild inflammation and bleeding Experiment c 10 No obvious inflammation, cysts, or bleeding Experiment d 15 No obvious inflammation, cysts, or bleeding Experiment e 20 No obvious inflammation, cysts, or bleeding Experiment f 25 minor bleeding

Table 3 below shows the hybrid porous microtubule fiber structure implanted under the skin of rabbits. After 12 weeks, the hybrid porous microtubule fiber structure and lymphatic vessel formation at different hole spacing were observed. The hole spacing refers to the two hybrid porous structures. The distance between the two circumferences of a microtubular fiber structure.

table 3 Hole spacing (μm) Implantation status after 12 weeks Experiment 1 2 Mild inflammation and bleeding Experiment 2 5 minor bleeding Experiment 3 10 No obvious inflammation, cysts, or bleeding Experiment 4 15 No obvious inflammation, cysts, or bleeding Experiment 5 20 No obvious inflammation, cysts, or bleeding Experiment 6 25 minor bleeding Experiment 7 30 Minor bleeding and cysts Experiment 8 35 Mild inflammation and cysts

From the results in Experimental Tables 2 to 3, the histopathological report of the 12-week rabbit subcutaneous implantation study is shown. At the same time, as shown in Figure 7, the red circle represents the cross-section of the hybrid porous microtubule fiber structure. The hybrid porous The diameter of the microtubular fiber structure. Under appropriate conditions, the fiber bundles of this bioactive glass fiber promote therapeutic lymphangiogenic healing in a manner that activates macrophage-derived lymphatic endothelial cell progenitor cells, and the subcutaneous implantation site is not Show obvious signs of inflammation, cysts, hemorrhage, necrosis or discoloration.

Please refer to Figure 8, which is a microscopic sequence photo image of human dental pulp stem cells (DPSC) grown using the biological glass fiber of the present invention.

As shown in Figure 8, the bioactive glass fiber has directionality. When human dental pulp stem cells (hDPSC) 3 are placed into the single bare fiber structure or the mixed fiber structure, the human dental pulp stem cells 3 will Grow along the bioactive glass fiber 201 . The growth time is shown in the lower left corner of each photo in Figure 8. When co-cultured with the bioactive glass fiber 201, after 16 hours, the human dental pulp stem cells 3 have tended to the bioactive glass fiber 201; after 18 hours, the human dental pulp The stem cells 3 have tended to the bioactive glass fiber 201; after 22 hours, the human dental pulp stem cells 3 will grow against the bioactive glass fiber 201; after 24 hours, the human dental pulp stem cells 3 will grow against the bioactive glass fiber 201 grow. The situation became more obvious after 48 hours. A large number of human dental pulp stem cells 3 grew close to the bioactive glass fiber 201.

However, the above descriptions are only preferred embodiments of the present invention and are not intended to limit the scope of patent protection of the present invention. Therefore, all equivalent changes made by using the contents of the description and drawings of the present invention are equally included in the rights of the present invention. Within the scope of protection, we will make it clear.

1:Single bare fiber structure 2:Mixed fiber structure 20: Hybrid solid fiber structure 201:Bioglass fiber 202:Bio-inert fiberglass 203: X-ray opaque bio-inert glass fiber 204: X-ray opaque bioactive glass fiber 20a: Mixed solid fiber structure 21: Hybrid single-hole microtube fiber structure 22: Hybrid porous microtubule fiber structure 221: Microtubule fiber 222:Hybrid Core 23: Single hole microtubule fiber structure 3: Human dental pulp stem cells

Figure 1 is a schematic diagram of a single bare fiber structure of the present invention; Figure 2A is a schematic diagram of the hybrid fiber structure of the present invention; Figure 2B is an SEM image of the hybrid solid fiber structure sample 1 of the present invention; Figure 2C is an SEM image of the hybrid solid fiber structure sample 2 of the present invention; Figure 2D is an SEM image of the hybrid solid fiber structure sample 3 of the present invention; Figure 2E is an SEM image of the hybrid solid fiber structure sample 4 of the present invention; Figure 2F is an SEM image of the hybrid solid fiber structure sample 5 of the present invention; Figure 3A is a cross-sectional SEM image of the single-hole microtubule fiber structure sample 1 of the present invention; Figure 3B is a cross-sectional SEM image of the single-hole microtube fiber structure sample 2 of the present invention; Figure 4A is a cross-sectional SEM image of the hybrid single-hole microtube fiber structure sample 1 of the present invention; Figure 4B is a cross-sectional SEM image of the hybrid single-hole microtube fiber structure sample 2 of the present invention; Figure 5A is a tip SEM image of the hybrid porous microtubular fiber structure of the present invention; Figure 5B is a cross-sectional SEM image of the hybrid porous microtubule fiber structure sample 1 of the present invention; Figure 5C is a cross-sectional SEM image of the hybrid porous microtubule fiber structure sample 2 of the present invention; Figure 6 is a photomicrograph image of histopathological sections of bioglass fibers and new lymphatic vessels used in regenerative medical materials according to the present invention; Figure 7 is a photomicrograph image of a histopathological section of a bioglass fiber subcutaneously implanted for regenerative medical materials according to the present invention; and Figure 8 is a microscopic sequence photo image of the bioglass fiber of the present invention applied to the growth of human dental pulp stem cells (DPSC).

without.

Claims (17)

A biological glass fiber used for regenerative medical materials, including a bioactive glass or a bioinert glass composed of a glass chemical composition. The glass chemical composition of the bioactive glass includes: 5~25wt% sodium oxide , 45~67wt% silicon dioxide, 15~25wt% calcium oxide and 2~6wt% phosphorus pentoxide, calculated based on the total weight percentage of 100wt% of the glass chemical composition; wherein, the glass chemical composition forms A single bare fiber structure and a mixed fiber structure. For the biological glass fiber described in item 1 of the patent application, the glass chemical composition of the bioactive glass further includes 1 to 8 wt% magnesium oxide and 8 to 12.5 wt% potassium oxide. As for the bioglass fiber described in item 1 of the patent application, the glass chemical composition of the bioinert glass includes 0.1~5wt% of non-toxic elements in the 5A group and 3B, 4B and 5B transition metal elements. The bioglass fiber described in item 1 of the patent application, wherein the single bare fiber structure is composed of the bioactive glass or the bioinert glass. As for the bioglass fiber described in claim 1, the hybrid fiber structure includes a single-hole microtube fiber structure composed of the bioactive glass or the bioinert glass. As for the bioglass fiber described in item 1 of the patent application, the hybrid fiber structure further includes a hybrid porous microtubular fiber structure composed of the bioactive glass or the bioinert glass. As for the bioglass fiber described in item 1 of the patent application, the hybrid fiber structure further includes a hybrid solid fiber structure composed of two or more layers of the bioactive glass, the bioinert glass, or a combination thereof. The bioglass fiber described in item 1 of the patent application, wherein the hybrid fiber structure further includes a hybrid single-hole microtube fiber composed of two or more layers of the bioactive glass, the bioinert glass, or a combination thereof. structure. The bioglass fiber as described in item 6 of the patent application, wherein the hybrid porous microtubular fiber structure is composed of two or more layers of the bioactive glass or the bioinert glass, and has a circular or a non-circular shape. Geometry of cross-section. The bio-glass fiber as described in item 1 of the patent application, wherein the single bare fiber structure and the hybrid fiber structure include an X-ray opaque bio-inert glass fiber. The biological glass fiber as described in item 1 of the patent application, wherein, based on the modification of the glass chemical composition or the diameter size parameters of the fiber components, the single bare fiber structure and the mixed fiber structure have different properties in human or animal organisms. of recycled material absorption time. As for the biological glass fiber described in item 1 of the patent application, the single bare fiber structure has a diameter of 3~25 μm. As for the bioglass fiber described in item 9 of the patent application, the hybrid porous microtubular fiber structure has a circular diameter of 3~35 μm. As for the bioglass fiber described in item 9 of the patent application, the pore diameter of the mixed porous microtubular fiber structure with a non-circular cross-section geometry is between 3 and 125 μm. An application of bio-glass fiber for regenerative medical materials. The bio-glass fiber is composed of a glass chemical composition as described in item 1 of the patent application scope. The application of the bio-glass fiber includes inducing therapeutic lymphangiogenesis. , or induce the directional arrangement and proliferation of stem cells, or induce stem cell regeneration, or induce bone cell regeneration, or induce neurovascular regeneration, or serve as a cell carrier. An application as described in claim 15, wherein the bioglass fiber activates macrophage-derived lymphatic endothelial cell progenitor cells and promotes lymphatic vessel regeneration and aqueous humor drainage through therapeutic lymphangiogenesis without fiber change. As described in item 15 of the patent application, the biological glass fiber is co-cultured with dental pulp stem cells (DPSCs) at a clinically effective time, so that the dental pulp stem cells tend to grow toward the biological glass fiber, and finally the dental pulp stem cells It will grow against the bioglass fibers and integrate into the odontoblasts that form dentin.