Absorbable internal fixation biomaterial and preparation method and application thereof

Abstract

The application provides an absorbable internal fixation biomaterial and a preparation method and application thereof, and the absorbable internal fixation biomaterial comprises 1-5 parts by weight of a natural nano-reinforced filler, 1-10 parts by weight of a reactive polymer and 80-90 parts by weight of a bio-based polymer matrix; the natural nano-reinforced filler and the reactive polymer are used to synergistically reinforce and toughen the bio-based polymer matrix, so that the obtained absorbable internal fixation biomaterial has excellent mechanical properties and degradable properties, can be applied as a biological medical material for orthopedics or dentistry, and has good economic benefits and practical significance.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to an absorbable internal fixation biomaterial, its preparation method, and its application. Background Technology

[0002] Biodegradable polymers have been widely used in surgical sutures, tissue engineering scaffolds, and orthopedic fixation materials. Among them, polylactic acid (PLA), a biodegradable polymer synthesized from biological resources, possesses excellent physical and mechanical properties and good biocompatibility. It is widely used in orthopedic, dental, and other surgical procedures. In particular, internal fixation materials made with PLA as the matrix material eliminate the need for secondary surgery after bone healing, effectively reducing patient suffering and becoming a current research hotspot. However, most bio-based polymers, including PLA, have high hardness and poor toughness, leading to brittleness and easy breakage in applications requiring toughness. Furthermore, due to insufficient mechanical properties, their degradation products are acidic, which can induce inflammatory responses in tissues during application.

[0003] Currently, natural nanofillers are commonly used to enhance the mechanical properties of polymers. Examples include chitin nanocrystals and cellulose nanocrystals. Both chitin and cellulose nanocrystals possess abundant chemical functional groups on their surfaces, allowing for various surface modifications to impart diverse properties and functions. Numerous studies have explored the addition of chitin and cellulose nanocrystals to aqueous matrices, such as natural rubber, gelatin, chitosan, and waterborne polyurethane, demonstrating significant mechanical strengthening effects. However, for hydrophobic matrices, such as polylactic acid (PLA), the difference in polarity leads to uneven dispersion of nanocrystals within the PLA system, resulting in minimal or no strengthening effect on PLA.

[0004] Therefore, developing an absorbable internal fixation biomaterial that combines excellent mechanical properties with biodegradability has become an urgent technical problem to be solved. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide an absorbable internal fixation biomaterial, its preparation method, and its applications. By employing natural nano-reinforcing fillers and reactive polymers to synergistically enhance and toughen the bio-based polymer matrix, the resulting absorbable internal fixation biomaterial possesses excellent mechanical properties and biodegradability, making it suitable for a wide range of applications.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides an absorbable internal fixation biomaterial, wherein the raw materials for preparing the absorbable internal fixation biomaterial comprise the following components in parts by weight:

[0008] 1-5 parts by weight of natural nano-reinforced filler;

[0009] 1-10 parts by weight of reactive polymer;

[0010] 80-90 parts by weight of bio-based polymer matrix.

[0011] The amount of the natural nano-reinforced filler can be 1.5 parts by weight, 2 parts by weight, 2.5 parts by weight, 3 parts by weight, 3.5 parts by weight, 4 parts by weight, or 4.5 parts by weight, etc.

[0012] The reactive polymer can be 2 parts by weight, 3 parts by weight, 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, or 9 parts by weight, etc.

[0013] The bio-based polymer matrix can be 81 parts by weight, 82 parts by weight, 83 parts by weight, 84 parts by weight, 85 parts by weight, 86 parts by weight, 87 parts by weight, 88 parts by weight, or 89 parts by weight, etc.

[0014] This invention utilizes natural nano-reinforcing fillers and reactive polymers to synergistically enhance and toughen a bio-based polymer matrix, thereby improving the crystallinity of the composite material. This results in the preparation of an absorbable internal fixation biomaterial that combines excellent mechanical strength with biodegradability. This material can meet the requirements for fracture fixation of weight-bearing bones and avoids problems such as acidic degradation products that easily cause inflammatory reactions in vivo, weak cell adhesion, and hindering bone growth, which are common in traditional Chinese medicine. It is suitable for use as a surgical biomedical material in orthopedics, dentistry, and other surgical fields.

[0015] Preferably, the natural nano-reinforcing filler includes any one or a combination of at least two of cellulose nanocrystals, chitin nanocrystals, epoxidized cellulose nanocrystals, or epoxidized chitin nanocrystals.

[0016] Preferably, the natural nano-reinforcing filler comprises epoxidized cellulose nanocrystals and / or epoxidized chitin nanocrystals.

[0017] As a preferred technical solution of the present invention, epoxidized cellulose nanocrystals and / or epoxidized chitosan nanocrystals are further selected as natural nano-reinforcing fillers. The epoxidized cellulose nanocrystals and / or epoxidized chitosan nanocrystals are obtained by acetylation and epoxidation modification, resulting in more amino groups exposed on the surface, which can enhance the antibacterial properties of the composite material. When used as a biomedical material, it can alleviate the inflammatory response of human tissues. At the same time, the epoxy groups contained on its surface can react with the end groups of the bio-based polymer matrix, such as the end groups of polylactic acid, and then connect the two through bridging, improving the interfacial connection strength. As the reaction continues, chain extension is achieved, realizing reactive compatibilization.

[0018] In this invention, there are no special restrictions on the source of the epoxidized cellulose nanocrystals. Exemplarily, they can be prepared by the following method, which includes: mixing cellulose nanocrystals, epichlorohydrin, NaOH solution and deionized water, reacting at 35-45°C, washing with distilled water until neutral after stopping the reaction, and then filtering and drying to obtain the epoxidized cellulose nanocrystals.

[0019] In this invention, the source of the epoxidized chitin nanocrystals is not particularly limited. Exemplarily, they can be prepared by the following method, which includes: mixing chitin and acetic acid solution to obtain a chitin-acetic acid solution, then adding NaOH solution for swelling, then adding epichlorohydrin solution for reaction, and finally washing repeatedly with distilled water until neutral to obtain the epoxidized chitin nanocrystals.

[0020] Preferably, the reactive polymer includes any one or a combination of at least two of polyethylene glycol, two-arm epoxidized polyethylene glycol, or multi-arm epoxidized polyethylene glycol.

[0021] Preferably, the reactive polymer comprises two-arm epoxidized polyethylene glycol and / or multi-arm epoxidized polyethylene glycol.

[0022] As a preferred technical solution of the present invention, double-arm epoxidized polyethylene glycol and / or multi-arm epoxidized polyethylene glycol are selected as reactive polymers. The epoxy groups contained therein can also crosslink and chain extend with the terminal groups of the bio-based polymer matrix, and have a synergistic effect with the natural nano-reinforcing filler to jointly enhance and toughen the bio-based polymer matrix, thereby further improving the mechanical properties of the absorbable internal fixation biomaterial.

[0023] In this invention, the source of the double-arm epoxidized polyethylene glycol is not particularly limited, and it can be prepared by means of the following method: mixing polyethylene glycol powder and NaOH aqueous solution in a flask, adding epichlorohydrin and benzyltriethylammonium chloride dropwise to the mixture for reaction, filtering the mixture after the reaction is completed, washing it with dichloromethane, drying it with anhydrous sodium sulfate to remove water, evaporating part of the dichloromethane, and recrystallizing it with methyl tert-butyl ether to obtain the double-arm epoxidized polyethylene glycol.

[0024] In this invention, the source of the multi-arm epoxidized polyethylene glycol is not particularly limited. It can be prepared by means of the following method: mixing lactide, glycolide, pentaerythritol and a dichloromethane solution containing a catalyst, removing the organic solvent under vacuum, and then reacting under a nitrogen atmosphere. After the reaction, the product is dissolved in dichloromethane, purified twice by precipitation with anhydrous methanol, and dried under vacuum overnight to obtain a four-armed star compound. The four-armed star compound and NaOH aqueous solution are then mixed in a flask, and epichlorohydrin and benzyltriethylammonium chloride are added dropwise to the mixture to react. After the reaction, the mixture is filtered, washed with dichloromethane, dried with anhydrous sodium sulfate to remove water, and after evaporating part of the dichloromethane, it is recrystallized with methyl tert-butyl ether to obtain the multi-arm epoxidized polyethylene glycol.

[0025] Preferably, the bio-based polymer matrix comprises any one or a combination of at least two of polylactic acid, polyethylene glycol, polyglycolic acid, or polycaprolactone.

[0026] Preferably, the bio-based polymer matrix comprises polylactic acid.

[0027] In a second aspect, the present invention provides a method for preparing the absorbable internal fixation material as described in the first aspect, the method comprising: mixing natural nano-reinforcing filler, reactive polymer and bio-based polymer matrix, and injection molding to obtain the absorbable internal fixation material.

[0028] Thirdly, the present invention provides an application of the absorbable internal fixation material as described in the first aspect as a biomedical material.

[0029] Preferably, the biomedical material includes orthopedic biomedical materials or dental biomedical materials.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The absorbable internal fixation biomaterial provided by this invention comprises a specific number of natural nano-reinforcing fillers, reactive polymers, and a bio-based polymer matrix. The natural nano-reinforcing fillers and reactive polymers are used synergistically to reinforce and toughen the bio-based polymer matrix, resulting in an absorbable internal fixation biomaterial that possesses both excellent mechanical properties and biodegradability. It can be used as a biomedical material in orthopedics or dentistry, and has good economic benefits and practical significance. Detailed Implementation

[0032] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0033] In the specific embodiments provided by this invention, the information on some of the raw materials involved is as follows:

[0034] Polyethylene glycol: purchased from Shanghai Aladdin Reagent Co., Ltd., P103731, with a number average molecular weight of 10,000;

[0035] Polylactic acid: purchased from Jinan Daigang Bioengineering Co., Ltd., with a weight-average molecular weight of 260,000.

[0036] Preparation Example 1

[0037] An epoxidized cellulose nanocrystal is prepared by means of: weighing 1g of cellulose nanocrystals and adding 55mL of distilled water, 7mL of epichlorohydrin and 6mL of 40wt% NaOH solution into an Erlenmeyer flask, then placing the Erlenmeyer flask in a constant temperature water bath shaker, shaking at 40℃ for 2.5h and then stopping the reaction, washing the reaction product with distilled water until neutral, then using sodium thiosulfate and phenolphthalein indicator to detect the epichlorohydrin in the effluent until the epichlorohydrin is washed away, filtering and washing twice with acetone, and finally drying at 50℃ to obtain the epoxidized cellulose nanocrystals.

[0038] Preparation Example 2

[0039] A method for preparing epoxidized chitin nanocrystals includes: preparing a 2.5% (w / v) chitin-acetic acid solution using a 1% (v / v) acetic acid solution, adding 50 mL of 1 mol / L NaOH solution to swell, then slowly adding 4 mL of epichlorohydrin solution and reacting for 24 h, and finally washing the reaction product repeatedly with distilled water until neutral to obtain the epoxidized chitin nanocrystals.

[0040] Preparation Example 3

[0041] A method for preparing cellulose nanocrystals includes: weighing 14.0 g of short cotton fibers and placing them in a 1000 mL beaker, adding 490 mL of 2 wt% NaOH solution, and mechanically stirring at room temperature for 12 h; filtering the resulting suspension using a Buchner funnel and washing until neutral, and drying at 45 °C; weighing 12.5 g of the dried product and placing it in a 500 mL flask, heating it in an oil bath at 45 °C, adding 250 mL of 65 wt% sulfuric acid, and reacting under mechanical stirring for 1 h; after the reaction is complete, adding ice water to terminate the reaction; centrifuging the resulting suspension for 10 min, removing it, discarding the supernatant, transferring the lower precipitate to a beaker, adding an appropriate amount of distilled water, homogenizing for 5 min, repeating the above steps twice; finally, dialyzing the centrifuged product for 5 days, and then freeze-drying the resulting suspension to obtain the cellulose nanocrystals.

[0042] Preparation Example 4

[0043] A method for preparing a two-arm epoxidized polyethylene glycol includes: mixing 2.7 g of polyethylene glycol powder and 12 g of 50 wt% NaOH aqueous solution in a flask; adding 0.3 mol of epichlorohydrin and 1 g of benzyltriethylammonium chloride dropwise to the mixture under vigorous stirring at 50 °C; stirring and reacting at 50 °C for 1 h; filtering the mixture after the reaction is complete; washing with dichloromethane; drying with anhydrous sodium sulfate to remove water; evaporating part of the dichloromethane; and finally recrystallizing with methyl tert-butyl ether to obtain the two-arm epoxidized polyethylene glycol.

[0044] Preparation Example 5

[0045] A multi-arm epoxidized polyethylene glycol, the preparation method of which includes the following steps:

[0046] (1) Add 5g lactide, 1.3g glycolide, 0.13g pentaerythritol and dichloromethane solution containing stannous octoate catalyst to a three-necked flask, evacuate to remove organic solvent, and purge with nitrogen gas for about 1 minute every 10 minutes, alternating more than 3 times. After sealing the tube, place it in a constant temperature oven at 160℃ for 8 hours. After the reaction is completed, dissolve the product in dichloromethane, precipitate and purify twice with anhydrous methanol, and dry under vacuum overnight to obtain a four-armed star-shaped compound.

[0047] (2) Then, 2.7g of the four-armed star-shaped compound obtained in step (1) and 12g of 50wt% NaOH aqueous solution are mixed in a flask. Under vigorous stirring at 50°C, 0.3mol of epichlorohydrin and 1g of benzyltriethylammonium chloride are added dropwise to the mixture. The mixture is stirred at 50°C for 1h. After the reaction is completed, the mixture is filtered, washed with dichloromethane, dried with anhydrous sodium sulfate to remove water, and after evaporating part of the dichloromethane, it is recrystallized with methyl tert-butyl ether to obtain the multi-armed epoxidized polyethylene glycol.

[0048] Example 1

[0049] An absorbable internal fixation biomaterial, the raw materials of which comprise the following components by weight:

[0050] Epoxidized cellulose nanocrystals, 3 parts by weight;

[0051] Five parts by weight of double-arm epoxidized polyethylene glycol;

[0052] 85 parts by weight of polylactic acid matrix;

[0053] The method for preparing the absorbable internal fixation biomaterial provided in this embodiment includes: thoroughly mixing epoxidized cellulose nanocrystals (Preparation Example 1), double-arm epoxidized polyethylene glycol (Preparation Example 4), and polylactic acid matrix, and extruding them in a single-screw injection molding machine at a nozzle temperature of 50°C, a barrel temperature of 105°C, a nozzle temperature of 125-140°C, and a mold temperature of 40°C to obtain the absorbable internal fixation biomaterial.

[0054] Example 2

[0055] An absorbable internal fixation biomaterial, the raw materials of which comprise the following components by weight:

[0056] 5 parts by weight of epoxidized chitosan nanocrystals;

[0057] 10 parts by weight of double-arm epoxidized polyethylene glycol;

[0058] 90 parts by weight of polylactic acid matrix;

[0059] The method for preparing the absorbable internal fixation biomaterial provided in this embodiment includes: thoroughly mixing epoxidized chitin nanocrystals (preparation example 2), double-arm epoxidized polyethylene glycol (preparation example 4), and polylactic acid matrix, and extruding them in a single-screw injection molding machine at a nozzle temperature of 50°C, a barrel temperature of 105°C, a nozzle temperature of 125-140°C, and a mold temperature of 40°C to obtain the absorbable internal fixation biomaterial.

[0060] Example 3

[0061] An absorbable internal fixation biomaterial, the raw materials of which comprise the following components by weight:

[0062] 1 part by weight of epoxidized chitosan nanocrystals;

[0063] One part by weight of multi-arm epoxidized polyethylene glycol;

[0064] 80 parts by weight of polylactic acid matrix;

[0065] The method for preparing the absorbable internal fixation biomaterial provided in this embodiment includes: thoroughly mixing epoxidized chitin nanocrystals (preparation example 2), multi-arm epoxidized polyethylene glycol (preparation example 5), and polylactic acid matrix, and extruding them in a single-screw injection molding machine at a nozzle temperature of 50°C, a barrel temperature of 105°C, a nozzle temperature of 125-140°C, and a mold temperature of 40°C to obtain the absorbable internal fixation biomaterial.

[0066] Example 4

[0067] An absorbable internal fixation biomaterial differs from Example 1 in that the amount of epoxidized cellulose nanocrystals (Preparation Example 1) added is 5 parts by weight, while the other components, amounts, and preparation methods are the same as in Example 1.

[0068] Example 5

[0069] An absorbable internal fixation biomaterial differs from Example 1 in that the amount of epoxidized cellulose nanocrystals (Preparation Example 1) added is 1 part by weight, while the other components, amounts, and preparation methods are the same as in Example 1.

[0070] Example 6

[0071] An absorbable internal fixation biomaterial differs from Example 1 in that cellulose nanocrystals (Preparation Example 3) are used instead of epoxidized cellulose nanocrystals (Preparation Example 1), while the other components, amounts, and preparation methods are the same as in Example 1.

[0072] Example 7

[0073] An absorbable internal fixation biomaterial differs from Example 1 in that polyethylene glycol is used instead of the double-arm epoxidized polyethylene glycol (Preparation Example 4), while the other components, amounts, and preparation methods are the same as in Example 1.

[0074] Example 8

[0075] An absorbable internal fixation biomaterial differs from Example 1 in that cellulose nanocrystals (Preparation Example 3) are used instead of epoxidized cellulose nanocrystals (Preparation Example 1), and polyethylene glycol is used instead of double-arm epoxidized polyethylene glycol (Preparation Example 4). Other components, amounts, and preparation methods are the same as in Example 1.

[0076] Comparative Example 1

[0077] An absorbable internal fixation biomaterial differs from Example 1 in that the raw materials used in its preparation contain only polylactic acid.

[0078] Comparative Example 2

[0079] An absorbable internal fixation biomaterial differs from Example 1 in that it does not contain epoxidized cellulose nanocrystals (Preparation Example 1), and the amount of double-armed epoxidized polyethylene glycol (Preparation Example 4) added is 8 parts by weight. Other components, amounts, and preparation methods are the same as in Example 1.

[0080] Comparative Example 3

[0081] An absorbable internal fixation biomaterial differs from Example 1 in that it does not contain double-arm epoxidized polyethylene glycol (Preparation Example 4), and the amount of epoxidized cellulose nanocrystals (Preparation Example 1) added is 8 parts by weight. Other components, amounts, and preparation methods are the same as in Example 1.

[0082] Comparative Example 4

[0083] An absorbable internal fixation biomaterial differs from Example 1 in that the amount of epoxidized cellulose nanocrystals (Preparation Example 1) added is 0.5 parts by weight, the amount of double-arm epoxidized polyethylene glycol (Preparation Example 4) added is 0.5 parts by weight, and the other components, amounts and preparation methods are the same as in Example 1.

[0084] Performance testing:

[0085] (1) Mechanical properties: Young's modulus, tensile strength and elongation at break were tested according to the test methods provided in the national standard GB / T 1040.3-2006;

[0086] (2) Biodegradability: The test was conducted according to the method provided in standard YY / T 0473-2004, and the mass retention rate after 3 months of biodegradation was calculated.

[0087] The absorbable internal fixation biomaterials provided in Examples 1-7 and Comparative Examples 1-4 were tested according to the above test methods. The test results are shown in Table 1.

[0088] Table 1

[0089]

[0090]

[0091] According to the data in Table 1:

[0092] The absorbable internal fixation biomaterial provided by this invention has excellent mechanical properties and excellent biodegradability.

[0093] Specifically, the absorbable internal fixation biomaterials provided in Examples 1-3 have a Young's modulus of 1203.2-150.98 MPa, a tensile strength of 12.3-16.7 MPa, an elongation at break of 7.3-8.7%, and biodegradability shows that the mass retention rate after 3 months of degradation is 97.30-98.32%.

[0094] Compared with Example 1, the Young's modulus and elongation at break of the absorbable internal fixation biomaterials provided in Examples 4-5 were both lower than those in Example 1, indicating that too much or too little epoxidized cellulose nanocrystals will have an adverse effect on the mechanical properties of the absorbable internal fixation biomaterials.

[0095] Compared with Example 1, the Young's modulus and elongation at break of the absorbable internal fixation biomaterials provided in Examples 6-8 were also lower than those in Example 1. This indicates that adding the biomaterials after epoxidation modification helps to enhance the mechanical properties of the absorbable internal fixation biomaterials.

[0096] Compared with Example 1, the absorbable internal fixation biomaterial provided in Comparative Example 1 contains only polylactic acid, and its Young's modulus and elongation at break are both low; the absorbable internal fixation biomaterials provided in Comparative Examples 2 and 3 also have a lower Young's modulus because only one toughening and reinforcing modifier is added; the absorbable internal fixation biomaterial provided in Comparative Example 4 also has a lower Young's modulus and elongation at break because the amount of epoxidized cellulose nanocrystals and double-arm epoxidized polyethylene glycol added is low.

[0097] The applicant declares that this invention illustrates an absorbable internal fixation biomaterial, its preparation method, and its application through the above embodiments. However, this invention is not limited to the above process steps, meaning that this invention does not necessarily rely on the above process steps to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials used in this invention, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

Claims

1. An absorbable internal fixation biomaterial, characterized in that, The raw materials for preparing the absorbable internal fixation biomaterial include the following components in parts by weight: 1-5 parts by weight of natural nano-reinforced filler; 1-10 parts by weight of reactive polymer; 80-90 parts by weight of bio-based polymer matrix; The natural nano-reinforced filler includes epoxidized cellulose nanocrystals and / or epoxidized chitin nanocrystals; The reactive polymers include two-arm epoxidized polyethylene glycol and / or multi-arm epoxidized polyethylene glycol; The bio-based polymer matrix includes a polylactic acid matrix.

2. A method for preparing the absorbable internal fixation material as described in claim 1, characterized in that, The preparation method includes: mixing natural nano-reinforced fillers, reactive polymers and bio-based polymer matrices, and then injection molding them to obtain the absorbable internal fixation material.

3. The application of the absorbable internal fixation material as described in claim 1 as a biomedical material.

4. The application according to claim 3, characterized in that, The biomedical materials include orthopedic or dental biomedical materials.

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