PLDLA / BGFs bone regeneration barrier membrane as well as preparation method and application thereof

Abstract

The invention discloses a PLDLA / BGFs bone regeneration barrier membrane and a preparation method and application thereof, the PLDLA / BGFs bone regeneration barrier membrane comprises poly (L-lactic acid-co-D, L-lactic acid) (PLDLA) and bioactive glass fibers (BGFs), and the addition amount of the bioactive glass fibers is 3%-10% of the weight of polylactic acid. The protective film is used for being implanted into the bone meal at the defect part of the alveolar bone, and bone tissue regeneration is promoted.

Description

Technical Field

[0001] The present invention relates to the field of biomedical materials, and particularly relates to a PLDLA / BGFs bone regeneration barrier membrane and its preparation method and application. Background Art

[0002] The regeneration and repair of bone defects have long been one of the challenges in the research of regenerative medicine. Craniomaxillofacial and alveolar bone defects caused by trauma, infection, tumor resection, congenital skeletal abnormalities, and disuse atrophy caused by long-term tooth loss will have a serious impact on the chewing function, appearance, and psychology of patients. The guided bone regeneration (GBR) technique is one of the most commonly used and effective methods for solving peri-implant bone defects clinically. Its principle is to use a barrier membrane at the bone defect site to maintain the osteogenic space, block the ingrowth of epithelial cells and fibroblasts with a faster proliferation rate, and ensure the growth of osteoblasts and blood vessels, thereby preventing the early ingrowth of fibrous connective tissue and bone resorption. At the same time, it provides a more suitable local environment for bone regeneration, enabling the regeneration function of bone tissue to be maximally exerted.

[0003] Barrier membranes can be divided into two types, namely absorbable barrier membranes and non-absorbable barrier membranes. The former has poor mechanical properties and is prone to absorption or collapse in the early stage, making it difficult to maintain a good bone regeneration space. The latter, such as a titanium metal membrane, has good mechanical properties and can provide an effective barrier effect, but it is difficult to shape and not easy to fit with tissues; and it cannot be absorbed and requires a second operation for removal, bringing additional pain to patients. We hope to explore a more ideal guided bone regeneration barrier membrane with good biocompatibility, mechanical properties, and biodegradability, so as to simplify the surgical procedures and times, and relieve the pain and economic burden of patients.

[0004] Poly(L-lactic acid-co-D,L-lactic acid) is a kind of polylactic acid commonly used in the preparation of absorbable barrier membranes. However, as a biodegradable polymer material, polylactic acid has problems of mismatched degradation rate and insufficient mechanical strength, and the lactic acid generated during the degradation process may cause a local acidic environment, causing discomfort to patients (such as a feeling of soreness). Therefore, it is of great significance to develop a periosteal material that can neutralize acidic degradation products and promote bone regeneration. Summary of the Invention

[0005] The object of the present invention is to provide a PLDLA / BGFs bone regeneration barrier membrane, which is used as a protective membrane for bone powder implanted in the alveolar bone defect site to promote bone tissue regeneration. The material of the bone regeneration barrier membrane is based on poly(L-lactic acid-co-D,L-lactic acid) (PLDLA) and bioactive glass fibers (BGFs). The bioactive glass fibers can improve the mechanical properties and biocompatibility of the PLDLA barrier membrane. At the same time, the alkaline degradation products of the bioactive alkaline fibers can neutralize the acidic degradation products of polylactic acid, avoiding discomfort caused by the local acidic environment and promoting bone tissue regeneration. Therefore, PLDLA can ensure that the PLDLA bone regeneration barrier membrane maintains good mechanical properties during the bone tissue healing process, providing good space maintenance and osteogenic conditions.

[0006] To achieve the above object, in the first aspect, the present invention provides a PLDLA / BGFs bone regeneration barrier membrane, which comprises poly(L-lactic acid-co-D,L-lactic acid) (PLDLA) and bioactive glass fibers (BGFs), wherein the addition amount of the bioactive glass fibers is 3%-10% of the weight of the polylactic acid.

[0007] Further, the bioactive glass fibers are selected from one or a combination of 45S5 bioactive glass and 58S bioactive glass.

[0008] Further, the diameter of the bioactive glass fibers is 50-1000 nm, and the aspect ratio is 10-100.

[0009] In the second aspect, the present invention provides a preparation method of a PLDLA / BGFs bone regeneration barrier membrane, which comprises one of 3D printing, extrusion molding, injection molding, wet pressing molding and co-blending hot pressing molding.

[0010] Further, the 3D printing comprises the following steps: weighing PLDLA and BGFs according to the ratio, extruding PLDLA and BGFs into filaments, and then performing customized molding by 3D printing.

[0011] Further, the extrusion molding comprises the following steps: weighing PLDLA and BGFs according to the ratio, mixing and extruding for granulation, extruding and molding into a film sheet with the required thickness, cutting and thermoforming for shaping.

[0012] Further, the injection molding comprises the following steps: weighing PLDLA and BGFs according to the ratio, mixing and extruding for granulation, and injection molding.

[0013] Further, the wet pressing and molding includes a crosslinking type and a solvent type; the crosslinking type wet pressing and molding includes the following steps: uniformly mixing PLDLA, BGFs, and a degradable adhesive, and performing hot pressing and molding through heating; the solvent type wet pressing and molding includes the following steps: uniformly mixing PLDLA, BGFs, and a solvent, dissolving PLDLA in the solvent, and performing drying and molding through heating in a mold.

[0014] Further, the blending and hot pressing molding includes the following steps:

[0015] (1) Weigh 100 parts of PLDLA and 3 - 10 parts of BGFs by weight, mix them uniformly to obtain a primary material;

[0016] (2) Extrude and granulate the primary material with a twin - screw extruder to obtain granulated material;

[0017] (3) Add the granulated material into a mold, perform hot pressing molding to obtain a PLDLA / BGFs bone regeneration barrier membrane.

[0018] Further, the temperature of the hot pressing molding is 145 - 155 °C, the pressure is 50 kgf, and the time is 30 - 40 min.

[0019] Further, the degradation period of the PLDLA / BGFs bone regeneration barrier membrane is 3 - 6 months.

[0020] In the third aspect, the present invention provides an application of a PLDLA / BGFs bone regeneration barrier membrane, which is used as a protective film for bone powder implanted in the alveolar bone defect site to promote bone tissue regeneration.

[0021] Technical effects

[0022] 1. The material of the bone regeneration barrier membrane of the present invention is based on polylactic acid and bioactive alkaline fibers. The bioactive glass fibers with a specific content can improve the processability, mechanical properties, and biocompatibility of the PLDLA barrier membrane. At the same time, the alkaline degradation products of the bioactive alkaline fibers can neutralize the acidic degradation products of polylactic acid, avoiding discomfort caused by the local acidic environment.

[0023] 2. The alkaline minerals (such as calcium ions) released by the bioactive alkaline fibers contribute to the mineralization and regeneration of bone tissue, providing good osteogenic conditions.

[0024] 3. The degradation rates of polylactic acid and bioactive alkaline fibers match the bone tissue regeneration rate, avoiding premature or delayed degradation of the material, and the degradation time matches the osteogenic healing time.

[0025] 4. The material of the bone regeneration barrier membrane has good biocompatibility and will not cause obvious inflammation or rejection reactions.

[0026] Other features and advantages of the present invention will become apparent from the following detailed description of exemplary embodiments of the invention. Detailed Description of the Invention

[0027] To make the above objects, features, and advantages of the invention more apparent and understandable, the following provides a detailed description of the specific embodiments of the invention.

[0028] In the following description, numerous specific details are set forth to facilitate a full understanding of the invention. However, the invention may be practiced in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the spirit of the invention. Therefore, the invention is not limited by the specific embodiments disclosed below.

[0029] The PLDLA / BGFs bone regeneration barrier membrane according to the present invention may include poly(L-lactic acid-co-D,L-lactic acid) (PLDLA) and bioactive glass fibers (BGFs), wherein the addition amount of the bioactive glass fibers is 3% - 10% of the weight of the polylactic acid. The bioactive glass fibers are selected from one or a combination of 45S5 bioglass and 58S bioglass. The diameter of the bioactive glass fibers is 50 - 1000 nm, and the aspect ratio is 10 - 100.

[0030] The preparation method of the PLDLA / BGFs bone regeneration barrier membrane according to the present invention may include one of 3D printing, extrusion molding, injection molding, wet pressing molding, and blend hot pressing molding.

[0031] In one embodiment, the 3D printing preparation method may include the following steps: weighing PLDLA and BGFs according to the ratio, extruding PLDLA and BGFs into filaments, and then performing customized molding by 3D printing.

[0032] In one embodiment, the extrusion molding preparation method may include the following steps: weighing PLDLA and BGFs according to the ratio, mixing and extruding into pellets, extruding into a film sheet with the required thickness, slitting, and thermoforming for sizing.

[0033] In one embodiment, the injection molding preparation method may include the following steps: weighing PLDLA and BGFs according to the ratio, mixing and extruding into pellets, and injection molding.

[0034] In one embodiment, the wet pressing molding preparation method may include a crosslinking type and a solvent type; the crosslinking type wet pressing molding may include the following steps: uniformly mixing PLDLA, BGFs, and a degradable adhesive, and performing hot pressing molding; the solvent type wet pressing molding may include the following steps: uniformly mixing PLDLA, BGFs, and a solvent, dissolving PLDLA in the solvent, and performing heating and drying molding in a mold.

[0035] The preparation method by blending and hot pressing according to the present invention comprises the following steps: (1) Weigh 100 parts of PLDLA and 3 - 10 parts of BGFs by weight, mix them evenly to obtain a preliminary material; (2) Extrude and granulate the preliminary material with a twin - screw extruder to obtain granulated materials; (3) Add the granulated materials into a mold, and perform hot pressing to obtain a PLDLA / BGFs bone regeneration barrier membrane. The temperature of the hot pressing is 145 - 155 °C, the pressure is 50 kgf, and the time is 30 - 40 min. The degradation period of the PLDLA / BGFs bone regeneration barrier membrane is 3 - 6 months.

[0036] The PLDLA / BGFs bone regeneration barrier membrane according to the present invention is used as a protective film for implanting bone powder at the alveolar bone defect site to promote bone tissue regeneration.

[0037] The following specifically describes the PLDLA / BGFs bone regeneration barrier membrane of the present invention, its preparation method and application through examples.

[0038] Example

[0039] (1) Weigh 100 parts of PLDLA and 3 - 10 parts of BGFs by weight, mix them evenly to obtain a preliminary material;

[0040] (2) Extrude and granulate the preliminary material with a twin - screw extruder to obtain granulated materials;

[0041] (3) Add the granulated materials into a mold, and perform hot pressing. The temperature of the hot pressing is 145 - 155 °C, the pressure is 50 kgf, and the time is 30 - 40 min to obtain a PLDLA / BGFs bone regeneration barrier membrane.

[0042] Performance test: After preparation and molding, observe the appearance of the finished product, and use it as a protective film for implanting bone powder at the alveolar bone defect site of patients, and follow - up the feelings of the patients during use. The performance test results are shown in Table 1.

[0043] Table 1 Performance test results

[0044]

[0045]

[0046] As can be seen from Table 1, the material of the bone regeneration barrier membrane of the present invention is based on polylactic acid and bioactive alkaline fibers. A specific content of bioactive glass fibers can improve the processability of the barrier membrane. The appearance is intact, the mechanical properties and biocompatibility are good, meeting the performance requirements for being used as a protective film for implanting bone powder at the alveolar bone defect site. No inflammatory reaction occurs. At the same time, the alkaline degradation products of the bioactive alkaline fibers can neutralize the acidic degradation products of polylactic acid, avoiding discomfort such as a sour feeling caused by the local acidic environment.

[0047] The embodiments of the present invention have been described above. The above description is exemplary and not exhaustive, and is also not limited to the disclosed embodiments. Many modifications and variations will be obvious to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments.

Claims

1. A PLDLA / BGFs bone regeneration barrier membrane, characterized in that: The invention comprises poly (L-lactic acid-co-D, L-lactic acid) (PLDLA) and bioactive glass fibers (BGFs), wherein the added amount of the bioactive glass fibers is 3%-10% of the weight of the polylactic acid.

2. The PLDLA / BGFs bone regeneration barrier membrane according to claim 1, characterized in that: The bioactive glass fiber is selected from one or a combination of 45S5 bioglass and 58S bioglass.

3. The PLDLA / BGFs bone regeneration barrier membrane according to claim 1, characterized in that: The bioactive glass fiber has a diameter of 50-1000 nm and an aspect ratio of 10-100.

4. The method for preparing the PLDLA / BGFs bone regeneration barrier membrane according to claim 1 or 2, characterized in that: It includes one of 3D printing, extrusion molding, injection molding, wet pressing molding and blending hot pressing molding.

5. The method for preparing the PLDLA / BGFs bone regeneration barrier membrane according to claim 4, characterized in that: The blending hot pressing molding comprises the following steps: (1) Weigh 100 parts of PLDLA and 3-10 parts of BGFs by weight, mix them evenly to obtain a primary material; (2) extruding the initial material into pellets using a twin-screw extruder to obtain pellets; (3) Adding the pellets into a mold and hot pressing to form a PLDLA / BGFs bone regeneration barrier membrane.

6. The method for preparing the PLDLA / BGFs bone regeneration barrier membrane according to claim 5, characterized in that: The temperature of the hot pressing molding is 145-155° C., the pressure is 50 kgf, and the time is 30-40 minutes.

7. The PLDLA / BGFs bone regeneration barrier membrane prepared according to any one of claims 1 to 3 or the preparation method according to any one of claims 4 to 6, characterized in that: Its degradation period is 3-6 months.

8. An application of a PLDLA / BGFs bone regeneration barrier membrane prepared by the preparation method according to any one of claims 1 to 3 or any one of claims 4 to 6, characterized in that: A protective membrane used to implant bone powder in alveolar bone defects to promote bone tissue regeneration.

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