Porous membrane material with active pro-healing function and preparation method and application thereof

Abstract

The application discloses a porous membrane material with an active healing function and a preparation method and application thereof, and belongs to the technical field of dental materials. The method of the application is characterized in that a solution A of polylactic acid, a solution B of polycaprolactone, a solution C of a surfactant and a dispersion liquid D of a carbon material are uniformly mixed, and the obtained mixed solution is cast on a bacterial cellulose membrane, and then cured into a film under the conditions of a temperature of 10-40 DEG C and a relative humidity of 40-95%, thereby obtaining the porous membrane material with the active healing function. The preparation method of the application can in-situ prepare the porous membrane material with asymmetric surface pores, internal communicating large pores and rich micropores on the bacterial cellulose membrane. When used as a guided bone regeneration barrier membrane, the porous membrane material can effectively block the growth of soft tissue cells into a bone defect area, maintain osteogenesis space, promote osteoblast adhesion and proliferation, has the active healing function, and is expected to efficiently promote bone tissue regeneration.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of dental materials, and particularly relates to a porous membrane material with an active healing function and a preparation method and application thereof. BACKGROUND

[0002] Repairing bone tissue defects has been a technical problem to be solved urgently and a research focus in oral and maxillofacial surgery. Guided bone regeneration technology is the most effective bone tissue augmentation technology for solving the problem of bone tissue defects in clinic. A barrier membrane is placed between the bone tissue defect area and the soft tissue to artificially establish a biological barrier. On the one hand, the barrier membrane prevents epithelial cells and fibroblasts with a faster migration speed from growing into the bone tissue defect area. On the other hand, the barrier membrane ensures the dominant growth of osteoblasts with a slower migration speed in the defect cavity, thereby achieving the repair of bone tissue defects.

[0003] At present, the barrier membranes used clinically include collagen membranes (Geistlich Bio-Gide), high-density polytetrafluoroethylene membranes (Cytoplast TXT-200), titanium-reinforced high-density polytetrafluoroethylene membranes (Cytoplast Ti-250), and polylactic acid membranes (Guidor), etc. Among them, the most widely used collagen membrane has an asymmetric structure, which prevents soft tissue cells from invading the defect area on the one hand and promotes the adhesion and proliferation of osteoblasts on the other hand.

[0004] However, when there are adverse factors for bone defect repair in the microenvironment (such as active oxygen aggregation at the bone defect site, damage to the biological electric environment, and bacterial invasion, etc.), the above-mentioned clinical barrier membranes cannot effectively "actively" remove these adverse factors, resulting in the difficulty of the barrier membranes in meeting the higher level of tissue repair needs, especially in patients with poor immune and regenerative functions, the bone regeneration effect is poor, and even the surgery may fail. SUMMARY

[0005] The application discloses a porous membrane material with an active healing function and a preparation method and application thereof, which effectively solves the technical problem that the existing barrier membranes cannot "actively" remove the adverse factors for bone defect repair and promote defect healing.

[0006] To achieve the above-mentioned purpose, the technical scheme of the application is as follows:

[0007] The first aspect of the application provides a preparation method of a porous membrane material with an active healing function, which comprises the following steps:

[0008] providing a solution A of polylactic acid, a solution B of polycaprolactone, a solution C of a surfactant, and a dispersion liquid D of a carbon material;

[0009] mixing the solution A, the solution B, the solution C, and the dispersion liquid D uniformly to obtain a mixed solution;

[0010] The mixed solution is poured on the bacterial cellulose membrane and solidified into a membrane under the conditions of a temperature of 10-40 DEG C and a relative humidity of 40%-95%, thereby obtaining a porous membrane material with an active healing promoting function.

[0011] In combination with the first aspect, preferably, the organic solvents used to form solution A, solution B, solution C and dispersion D are each the same or different and are one of dichloromethane, chloroform, tetrahydrofuran and toluene.

[0012] In combination with the first aspect, preferably, the mass concentration of polylactic acid in solution A is 0.5-5 wt%, the mass concentration of polycaprolactone in solution B is 2-20 wt%, and the mass concentration of surfactant in solution C is 0.5-5 wt%.

[0013] In combination with the first aspect, preferably, the mass concentration of the carbon material in the dispersion D is 0.15 to 5 wt %.

[0014] In combination with the first aspect, preferably, the molecular weights of polylactic acid and polycaprolactone are both 8,000 to 800,000.

[0015] In combination with the first aspect, preferably, the surfactant is one of polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer, polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer, behenyldimethylammonium bromide, sodium dodecylbenzenesulfonate or lauryl betaine.

[0016] In combination with the first aspect, preferably, the carbon material is one of carbon nanospheres, carbon nanotubes, carbon black, activated carbon or graphene.

[0017] The second aspect of the present application provides a porous membrane material with an active healing promoting function prepared by the method described in the first aspect.

[0018] The third aspect of the embodiments of the present application provides the use of the porous membrane material with active healing-promoting function prepared by the method described in the first aspect as a barrier membrane for guided bone regeneration.

[0019] A fourth aspect of an embodiment of the present application provides a guided bone regeneration barrier membrane, which comprises a porous membrane material with an active healing-promoting function prepared by the method described in the first aspect.

[0020] Compared with the prior art, the advantages or beneficial effects of the embodiments of the present application include at least:

[0021] 1) The preparation method provided in the first aspect of the present application utilizes the "phase separation-breathing diagram combined strategy" to effectively prepare in situ a superstructured porous membrane with asymmetric surface pores, internally connected macropores and abundant micropores on a dense bacterial cellulose membrane. On the one hand, the loose surface of the porous membrane forms a macroporous morphology, which has the effect of promoting the adhesion and proliferation of osteoblasts; on the other hand, the dense surface of the porous membrane can block the penetration of soft tissue cells to maintain the osteogenic space; thirdly, phase separation occurs during the membrane formation process to induce the formation of a large number of connected pores inside, so that the porous membrane not only has the function of transporting nutrients, but also can effectively expose its internal active sites, providing a structural basis for the active promotion of healing effect; fourthly, porous carbon nanospheres can be effectively introduced into the porous membrane, so that the superstructured membrane has a macropore-micropore superstructure, which can actively remove reactive oxygen that is not conducive to healing, enhance electrical transmission and build a cell communication network, and kill bacteria, thereby efficiently promoting bone tissue regeneration.

[0022] 2) The porous membrane material with active healing function provided in the second aspect of the present application is capable of in situ preparing an asymmetric porous membrane with both macropores and micropores on a dense bacterial cellulose membrane based on the preparation method of the first aspect, and introducing porous carbon nanospheres into the asymmetric porous membrane to finally obtain a porous membrane with a superstructure. Therefore, the porous membrane of the present application not only has the function of actively removing reactive oxygen species that are not conducive to healing, enhancing electrical transmission and building a cell communication network, and killing bacteria, but also can transmit nutrients and expose internal active sites, which is expected to efficiently promote bone tissue regeneration.

[0023] 3) When the porous membrane material with an active healing-promoting function provided in the third aspect of the present application is used as a guided bone regeneration barrier membrane, the porous membrane has the functions of actively removing reactive oxygen species that are not conducive to healing, enhancing electrical transmission, building a cell communication network, and killing bacteria. Therefore, after the porous membrane material with an active healing-promoting function of the present application is used as a guided bone regeneration barrier membrane, the guided bone regeneration barrier membrane can have the biological effect of actively promoting healing while having the function of barrier soft tissue cells to protect the osteoblast space and promote osteoblast adhesion and proliferation. It effectively solves the technical difficulty that the current barrier membrane lacks the biological effect of actively promoting healing, and realizes the multifunctionality of barrier cells to maintain space, promote cell adhesion, and actively promote healing, which is more conducive to the repair of bone tissue defects in clinical practice.

[0024] 4) The guided bone regeneration barrier membrane provided in the fourth aspect of this application, based on the porous membrane material with active healing-promoting function of this application, has the functions of actively removing reactive oxygen species that are detrimental to healing, enhancing electrical transmission, building a cell communication network, and killing bacteria. Therefore, this guided bone regeneration barrier membrane is used in the clinical repair of bone tissue defects. On the one hand, it can protect soft tissue cells to protect the osteoblast space and promote osteoblast adhesion and proliferation; on the other hand, it can effectively remove reactive oxygen species that are detrimental to healing, enhance electrical transmission, build a cell communication network, and kill invading bacteria, thereby effectively promoting bone tissue regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] To more clearly illustrate the technical solutions of the embodiments of this application, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some of the embodiments described in this application. For those skilled in the art, other drawings can be derived from these drawings without inventive effort.

[0026] Figure 1 A physical image of the SPM1 provided in the embodiments of this application;

[0027] Figure 2 This is a SEM image of the loose surface of SPM1 provided in the examples of the present application;

[0028] Figure 3 This is a SEM image of the dense surface of SPM1 provided in the examples of the present application;

[0029] Figure 4 This is a SEM image of a cross section of SPM1 provided in an embodiment of the present application;

[0030] Figure 5 The time-scavenging percentage curve of 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) free radical by JPM and SPM1 provided in the examples of the present application;

[0031] Figure 6 The electrical conductivity of JPM, SPM1 and SPM10 provided in the examples of this application in dry and wet states;

[0032] Figure 7 Temperature-time curves of JPM and SPM1 provided in the examples of this application under 808nm laser irradiation;

[0033] Figure 8 These are micro-CT images of the wounds 2 months after the rat skull defect was repaired using BC, JPM, and SPM1 as provided in the examples of this application. DETAILED DESCRIPTION

[0034] The following will be combined with the accompanying drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the described embodiments are part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0035] In the following description of this embodiment, the term "and / or" is used to describe the association relationship between associated objects, indicating that three possible relationships exist. For example, A and / or B can represent: A exists alone, B exists alone, and both A and B exist. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0036] In the following description of this embodiment, the term "at least one" refers to one or more, and "plurality" refers to two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b, or c", or "at least one of a, b, and c" can all represent: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple.

[0037] Those skilled in the art should understand that in the following description of the embodiments of the present application, the order of serial numbers does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0038] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise.

[0039] In a first aspect, the present invention provides a method for preparing a porous membrane material having an active healing promoting function, the method comprising the following steps:

[0040] Providing a polylactic acid solution A, a polycaprolactone solution B, a surfactant solution C, and a carbon material dispersion D;

[0041] Mix solution A, solution B, solution C and dispersion D to obtain a mixed solution;

[0042] The mixed solution is poured on the bacterial cellulose membrane and solidified into a membrane under the conditions of a temperature of 10-40 DEG C and a relative humidity of 40%-95%, thereby obtaining a porous membrane material with an active healing promoting function.

[0043] The preparation method of the embodiment of the present application utilizes a "phase separation-breathing diagram combined strategy" to effectively prepare in situ asymmetric superstructured porous membranes with both macropores and micropores on dense bacterial cellulose membranes. In this process, a mixed solution of polylactic acid, polycaprolactone, a surfactant, and a carbon material is cooled in a humid atmosphere due to the rapid evaporation of the organic solvent, causing the surface temperature of the mixed solution to decrease. Water vapor condenses into water droplets and arranges on the surface of the mixed solution, which, after evaporation, forms a macroporous morphology on the membrane surface. Simultaneously, phase separation of the polymer during the film-forming stage is utilized to form a large number of interconnected pores inside the membrane, ultimately resulting in a superstructured porous membrane. In view of this, the porous membrane material with active healing promotion function in the embodiment of the present application has a dense surface on the one hand, which can prevent the penetration of soft tissue cells and protect the osteogenesis process; on the other hand, it has a loose surface with large pores and interconnected pores, which is conducive to the adhesion and proliferation of osteoblasts, and the interconnected pores ensure the normal transmission of nutrients and the effective exposure of internal active sites, thereby providing a structural basis for the active healing promotion effect; the third aspect is to introduce porous carbon nanospheres with rich micropores into the porous membrane. With the help of the large specific surface area of ​​carbon nanospheres and the characteristics of the carbon skeleton, the membrane is provided with adsorption, conductivity and photothermal properties, so that the porous membrane has the ability to actively remove active oxygen that is not conducive to healing, enhance electrical transmission and build a cell communication network, and kill bacteria, thereby achieving a barrier soft tissue cell to protect the osteogenesis space, promote osteoblast adhesion and proliferation, and also has the biological effect of actively promoting healing.

[0044] It should be noted that the curing temperature for film formation is preferably 25°C, the relative humidity is preferably 75%, and the film formation time is 6 hours. At this temperature and humidity, the volatilization rate of the organic solvent is moderate, and the volatilization of the organic solvent can effectively reduce the surface temperature of the solution. At the same time, the humidity can ensure that an appropriate amount of water vapor condenses and aligns on the surface of the solution, avoiding the destruction of the surface macropore morphology caused by excessive or insufficient water vapor. In addition, a film formation time of 6 hours ensures that the organic solvent and condensed water can fully evaporate, while also helping to save costs.

[0045] It should be noted that when preparing polylactic acid solution A, polycaprolactone solution B, and surfactant solution C, polylactic acid, polycaprolactone, and surfactant can be added to the same or different organic solvents at room temperature and stirred for 2 hours until completely dissolved.

[0046] It should be noted that when preparing dispersion D, the carbon material can be added to an organic solvent and ultrasonically dispersed for at least 10 minutes, so that the carbon material can be uniformly dispersed in the organic solvent and a stable dispersion system is formed. Based on comprehensive cost and dispersion effect considerations, the ultrasonic dispersion time is preferably 60 minutes.

[0047] It should be noted that before dispersing the mixed solution on the bacterial cellulose membrane, the bacterial cellulose membrane is first spread on the mold surface for drying. The drying temperature is preferably 4-60°C and the drying time is not less than 0.5h; more preferably, the drying temperature is 25°C and the drying time is 12h, so that the bacterial cellulose membrane can not only be completely dried, but also avoid the destruction of the microscopic morphology due to high temperature, which affects the soft tissue cell barrier effect of the prepared membrane.

[0048] It should be noted that the surfactant includes a nonionic surfactant, a cationic surfactant, an anionic surfactant, or a zwitterionic surfactant, and can be any of polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer (P123), polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer (F127), behenyldimethylammonium bromide, sodium dodecylbenzenesulfonate, or lauryl betaine. Among them, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer (P123) is preferably used, so that the prepared superstructure membrane can effectively stabilize condensed water droplets in humid air while ensuring phase separation into internal interconnected channels.

[0049] In conjunction with the first aspect, the organic solvents used to form solution A, solution B, solution C, and dispersion D are each, or are different, selected from the group consisting of dichloromethane, chloroform, tetrahydrofuran, and toluene. These organic solvents are capable of fully dissolving or dispersing polylactic acid, polycaprolactone, surfactants, and carbon materials, are highly volatile, and can evaporate rapidly in a humid atmosphere, thereby lowering the surface temperature of the mixed solution. This in turn causes water vapor in the air to condense into water droplets that align on the surface of the mixed solution, ultimately forming a macroporous morphology on the surface of the superstructure membrane. The organic solvent is preferably dichloromethane.

[0050] In combination with the first aspect, the mass concentration of polylactic acid in solution A is preferably 0.5-5 wt %, the mass concentration of polycaprolactone in solution B is preferably 2-20 wt %, and the mass concentration of surfactant in solution C is preferably 0.5-5 wt %.

[0051] In combination with the first aspect, the mass concentration of the carbon material in the dispersion D is 0.15 to 5 wt %.

[0052] It should be noted that, in the formed mixed solution, solution A accounts for 10% to 80% of the total solution volume, solution B accounts for 0 to 30% of the total solution volume, solution C accounts for 0 to 30% of the total solution volume, and dispersion D accounts for 0 to 50% of the total solution volume.

[0053] In combination with the first aspect, the molecular weights of both polylactic acid and polycaprolactone are preferably 8,000 to 800,000.

[0054] In conjunction with the first aspect, the carbon material in the embodiments of the present application is preferably any one of carbon nanospheres, carbon nanotubes, carbon black, activated carbon, or graphene. These carbon materials have excellent adsorption, electrical conductivity, and photothermal properties, and can actively remove reactive oxygen species that are detrimental to healing, enhance electrical transmission, build cell communication networks, and kill bacteria, thereby forming a barrier to protect the osteoblastic space, promote adhesion and proliferation, and actively promote healing. Among them, the carbon material is more preferably carbon nanospheres, which can help improve the adsorption and photothermal effects of the prepared porous membrane material.

[0055] On the second aspect, the embodiment of the present application provides a porous membrane material with an active healing-promoting function prepared by the above-mentioned preparation method. Based on the preparation method, an asymmetric porous membrane material with interconnected macropores capable of transmitting nutrients and exposing internal active sites can be prepared in situ on a dense bacterial cellulose membrane, and porous carbon nanospheres are introduced into the membrane material to form a porous membrane material with a superstructure. Therefore, the porous membrane of the embodiment of the present application not only has a barrier to protect the osteoblast space, promote adhesion and proliferation, but also can actively remove reactive oxygen species that are not conducive to healing, enhance electrical transmission, build a cell communication network and kill bacteria, and is expected to efficiently promote bone tissue regeneration.

[0056] On the third aspect, the present application provides that the porous membrane material with active healing function prepared by the above method is used as a guided bone regeneration barrier membrane, based on the porous membrane, it can actively remove reactive oxygen species that are not conducive to healing, enhance electrical transmission and build a cell communication network, kill bacteria, and be able to transmit nutrients and expose active sites. Therefore, after the porous membrane material with active healing function of the embodiment of the present application is used as a guided bone regeneration barrier membrane, the guided bone regeneration barrier membrane can have both a barrier to protect the osteoblastic space, promote adhesion and proliferation, and can also actively remove reactive oxygen species that are not conducive to healing, enhance electrical transmission and build a cell communication network and kill bacteria, effectively solving the technical difficulties of the current guided bone regeneration barrier membrane lacking an active healing biological effect, and achieving both a barrier to protect the osteoblastic space, promote adhesion and proliferation and an active healing effect, which is more conducive to the repair of bone tissue defects clinically.

[0057] Fourthly, the embodiments of the present application provide a barrier membrane for guided bone regeneration, based on the porous membrane material with the active healing-promoting function that can actively remove reactive oxygen species that are not conducive to healing, enhance electrical transmission and build a cell communication network, kill bacteria and transmit nutrients, and expose active sites. Therefore, in the clinical repair of bone tissue defects, the barrier membrane for guided bone regeneration, on the one hand, prevents soft tissue cells from invading the defect area to protect the osteoblastic space and promote osteoblast adhesion and proliferation; on the other hand, it can effectively remove reactive oxygen species that are not conducive to healing, enhance electrical transmission and build a cell communication network, and kill invading bacteria, etc., thereby efficiently promoting bone tissue regeneration. Among them, the barrier membrane includes dental barrier membranes and orthopedic barrier membranes, etc.

[0058] The technical solution of the present application will be further described below in conjunction with specific embodiments.

[0059] Example 1

[0060] This embodiment provides a method for preparing a porous membrane material SPM1 with an active healing promoting function, comprising steps S101 to S104.

[0061] S101: dissolving polylactic acid, polycaprolactone, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane, respectively, to prepare a polylactic acid solution with a concentration of 1.5 wt%, a polycaprolactone solution with a concentration of 5.7 wt%, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt%;

[0062] S102: adding the carbon nanospheres to dichloromethane and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0063] S103: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S101 and the dispersion prepared in step S102 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0064] S104: After the bacterial cellulose membrane is spread on the mold surface and dried at a temperature of 25°C for 12 hours, the mixed solution obtained in step S103 is evenly poured on the dried bacterial cellulose membrane and cured into a film for 6 hours at a temperature of 25°C and a relative humidity of 75%, thereby obtaining a porous membrane material SPM1 with active healing function.

[0065] Example 2

[0066] This embodiment provides a method for preparing a porous membrane material SPM2 having an active healing promoting function, comprising the following steps S201 to S204.

[0067] S201: dissolving polylactic acid, polycaprolactone, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane, respectively, to prepare a polylactic acid solution with a concentration of 5.0 wt%, a polycaprolactone solution with a concentration of 5.7 wt%, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt%;

[0068] S202: adding the carbon nanospheres to dichloromethane and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0069] S203: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S201 and the dispersion prepared in step S202 in a volume ratio of 48:8:10:34 and stirring to obtain a mixed solution;

[0070] S204: After the bacterial cellulose membrane is spread on the mold surface and dried at a temperature of 25°C for 12 hours, the mixed solution obtained in step S203 is evenly poured on the dried bacterial cellulose membrane and cured into a film for 6 hours at a temperature of 25°C and a relative humidity of 75%, thereby obtaining a porous membrane material SPM2 with active healing function.

[0071] Example 3

[0072] This embodiment provides a method for preparing a porous membrane material SPM3 with an active healing promoting function, comprising the following steps S301 to S304.

[0073] S301: dissolving polylactic acid, polycaprolactone, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane, respectively, to prepare a polylactic acid solution with a concentration of 1.5 wt%, a polycaprolactone solution with a concentration of 20 wt%, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt%;

[0074] S302: adding the carbon nanospheres to dichloromethane and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0075] S303: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S301 and the dispersion prepared in step S302 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0076] S304: After the bacterial cellulose membrane is laid on the surface of the mold and dried at a temperature of 25℃ for 12h, the mixed solution obtained in step S303 is uniformly poured on the dried bacterial cellulose membrane, and cured into a film under the condition of a temperature of 25℃ and a relative humidity of 75% for 6h, thereby obtaining the porous membrane material SPM3 with the active healing function.

[0077] Example 4

[0078] The present embodiment provides a preparation method of the porous membrane material SPM4 with the active healing function, comprising the following steps S401 to S404.

[0079] S401: Polylactic acid, polycaprolactone and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer are respectively dissolved in dichloromethane to prepare a polylactic acid solution with a concentration of 1.5wt%, a polycaprolactone solution with a concentration of 5.7wt% and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 3.0wt% in sequence;

[0080] S402: Carbon nanospheres are added into dichloromethane for ultrasonic dispersion, and the ultrasonic time is not less than 10min to prepare a dispersion liquid with a concentration of 0.29wt%;

[0081] S403: The polylactic acid solution, the polycaprolactone solution, the polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S401 and the dispersion liquid prepared in step S402 are mixed in a volume ratio of 48:8:10:34 and uniformly stirred to obtain a mixed solution;

[0082] S404: After the bacterial cellulose membrane is laid on the surface of the mold and dried at a temperature of 25℃ for 12h, the mixed solution obtained in step S403 is uniformly poured on the dried bacterial cellulose membrane, and cured into a film under the condition of a temperature of 25℃ and a relative humidity of 75% for 6h, thereby obtaining the porous membrane material SPM4 with the active healing function.

[0083] Example 5

[0084] The present embodiment provides a preparation method of the porous membrane material SPM5 with the active healing function, comprising the following steps S501 to S504.

[0085] S501: Polylactic acid, polycaprolactone and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer are respectively dissolved in dichloromethane to prepare a polylactic acid solution with a concentration of 1.5wt%, a polycaprolactone solution with a concentration of 5.7wt% and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5wt% in sequence;

[0086] S502: adding the carbon nanospheres to dichloromethane and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 5.0 wt %;

[0087] S503: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S501 and the dispersion prepared in step S502 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0088] S504: After the bacterial cellulose membrane is spread on the mold surface and dried at a temperature of 25°C for 12 hours, the mixed solution obtained in step S503 is evenly poured on the dried bacterial cellulose membrane and cured into a film for 6 hours at a temperature of 25°C and a relative humidity of 75%, thereby obtaining a porous membrane material SPM5 with active healing function.

[0089] Example 6

[0090] This embodiment provides a method for preparing a porous membrane material SPM6 with an active healing promoting function, comprising the following steps S601 to S604.

[0091] S601: dissolving polylactic acid, polycaprolactone, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane, respectively, to prepare a polylactic acid solution with a concentration of 1.5 wt%, a polycaprolactone solution with a concentration of 5.7 wt%, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt%;

[0092] S602: adding the carbon nanotubes to dichloromethane and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0093] S603: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S601 and the dispersion prepared in step S602 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0094] S604: Spread the bacterial cellulose membrane on the mold surface and dry it at 25°C for 12 hours. Then, pour the mixed solution obtained in step S603 evenly on the dried bacterial cellulose membrane, and solidify it into a membrane at a temperature of 25°C and a relative humidity of 75% for 6 hours to obtain a porous membrane material SPM6 with active healing function.

[0095] Example 7

[0096] This embodiment provides a method for preparing a porous membrane material SPM7 with an active healing promoting function, comprising the following steps S701 to S704.

[0097] S701: dissolving polylactic acid, polycaprolactone, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane, respectively, to prepare a polylactic acid solution with a concentration of 1.5 wt%, a polycaprolactone solution with a concentration of 5.7 wt%, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt%;

[0098] S702: adding carbon black to dichloromethane and performing ultrasonic dispersion for not less than 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0099] S703: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S701 and the dispersion prepared in step S702 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0100] S704: After the bacterial cellulose membrane is spread on the mold surface and dried at a temperature of 25°C for 12 hours, the mixed solution obtained in step S703 is evenly poured on the dried bacterial cellulose membrane and cured into a film for 6 hours at a temperature of 25°C and a relative humidity of 75%, thereby obtaining a porous membrane material SPM7 with active healing function.

[0101] Example 8

[0102] This embodiment provides a method for preparing a porous membrane material SPM8 with an active healing promoting function, comprising the following steps S801 to S804.

[0103] S801: dissolving polylactic acid, polycaprolactone, and polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer in dichloromethane, respectively, to prepare a polylactic acid solution with a concentration of 1.5 wt%, a polycaprolactone solution with a concentration of 5.7 wt%, and a polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer solution with a concentration of 1.5 wt%;

[0104] S802: adding the carbon nanospheres to dichloromethane and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0105] S803: mixing the polylactic acid solution, polycaprolactone solution, polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer solution prepared in step S801 and the dispersion prepared in step S802 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0106] S804: After the bacterial cellulose membrane is spread on the mold surface and dried at a temperature of 25°C for 12 hours, the mixed solution obtained in step S803 is evenly poured on the dried bacterial cellulose membrane and cured into a film for 6 hours at a temperature of 25°C and a relative humidity of 75%, thereby obtaining a porous membrane material SPM8 with active healing function.

[0107] Example 9

[0108] This embodiment provides a method for preparing a porous membrane material SPM9 with an active healing promoting function, comprising the following steps S901 to S904.

[0109] S901: dissolving polylactic acid, polycaprolactone, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in chloroform, respectively, to prepare a polylactic acid solution with a concentration of 1.5 wt%, a polycaprolactone solution with a concentration of 5.7 wt%, and a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt%;

[0110] S902: adding the carbon nanospheres to chloroform and performing ultrasonic dispersion for at least 10 minutes to prepare a dispersion having a concentration of 0.29 wt %;

[0111] S903: mixing the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S901 and the dispersion prepared in step S902 in a volume ratio of 48:8:10:34 and stirring uniformly to obtain a mixed solution;

[0112] S904: Spread the bacterial cellulose membrane on the mold surface and dry it at 25°C for 12 hours. Then, pour the mixed solution obtained in step S903 evenly on the dried bacterial cellulose membrane, and solidify it into a film at a temperature of 25°C and a relative humidity of 75% for 6 hours to obtain the porous membrane material SPM9 with active healing function.

[0113] Example 10

[0114] This embodiment provides a method for preparing a porous membrane material SPM10 with an active healing promoting function, comprising the following steps S1001 to S1004.

[0115] S1001: Dissolve polylactic acid, polycaprolactone and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane respectively, and prepare polylactic acid solution with a concentration of 1.5 wt%, polycaprolactone solution with a concentration of 5.7 wt% and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt% in sequence;

[0116] S1002: Add carbon nanospheres into dichloromethane for ultrasonic dispersion, and the ultrasonic time is not less than 10 min to prepare a dispersion liquid with a concentration of 0.15 wt%;

[0117] S1003: Mix the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S1001 and the dispersion liquid prepared in step S1002 in a proportion of 48:8:10:34 by volume ratio and stir uniformly to obtain a mixed solution;

[0118] S1004: Place a bacterial cellulose membrane on the surface of a mold and dry at a temperature of 25℃ for 12 h, then pour the mixed solution obtained in step S1003 uniformly on the dried bacterial cellulose membrane, and solidify into a film under the condition of a temperature of 25℃ and a relative humidity of 75% for 6 h to obtain a porous membrane material SPM10 with active healing function.

[0119] Example 11

[0120] The present embodiment provides a preparation method of asymmetric porous membrane JPM, comprising the following steps S1101 to S1103.

[0121] S1101: Dissolve polylactic acid, polycaprolactone and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer in dichloromethane respectively, and prepare polylactic acid solution with a concentration of 1.5 wt%, polycaprolactone solution with a concentration of 5.7 wt% and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution with a concentration of 1.5 wt% in sequence;

[0122] S1102: Mix the polylactic acid solution, polycaprolactone solution, polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer solution prepared in step S1101 and dichloromethane in a proportion of 48:8:10:34 by volume ratio and stir uniformly to obtain a mixed solution;

[0123] S1103: Place a bacterial cellulose membrane on the surface of a mold and dry at a temperature of 25℃ for 12 h, then pour the mixed solution obtained in step S1103 uniformly on the dried bacterial cellulose membrane, and solidify into a film under the condition of a temperature of 25℃ and a relative humidity of 75% for 6 h to obtain an asymmetric porous membrane JPM.

[0124] In order to verify the technical effect of the porous membrane with active healing function prepared in the examples of this application, this application characterizes the various properties of the porous membrane material SPM1 with active healing function prepared in Example 1, as follows:

[0125] 1. Appearance Characterization

[0126] The appearance of SPM1 was characterized, and the results were Figure 1 .in, Figure 1 This is a physical picture of SPM1.

[0127] according to Figure 1 It can be seen that one side of SPM1 is a loose side, and the other side is a dense side of bacterial cellulose.

[0128] 2. Characterization of surface and internal morphology

[0129] The surface morphology and internal morphology of SPM1 were observed using a scanning electron microscope (SEM). Figures 2 to 4 As shown. Among them, Figure 2 SEM image of the loose surface of SPM1; Figure 3 SEM image of the dense surface of SPM1; Figure 4 This is a SEM image of the cross section of SPM1.

[0130] according to Figures 2 to 3 It can be seen that the loose surface of SPM1 presents a micron-scale macroporous morphology, which is expected to promote the adhesion and proliferation of osteoblasts; at the same time, the dense surface of bacterial cellulose presents a nanoscale dense pore morphology, which is expected to block the penetration of soft tissue cells, thereby protecting the osteogenic space from interference.

[0131] according to Figure 4 It can be seen that there are a large number of interconnected channels inside SPM1, which not only enables SPM1 to transport nutrients, but also exposes internal active sites.

[0132] 3. Characterization of Reactive Oxygen Species Scavenging Performance

[0133] This application tests the effectiveness of SPM1 in removing 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH). The experimental process is as follows:

[0134] After vacuum drying, JPM and SPM1 were added with DPPH ethanol solution respectively and shaken at 37 °C;

[0135] Samples were taken at multiple times and the absorbance of the solution was measured, recorded as A t The absorbance of 100 μM DPPH ethanol solution was recorded as A0, and the DPPH clearance rate was calculated according to the following formula (1):

[0136] DPPH scavenging ratio = (A0-A t ) / A0×100%(1)

[0137] The result is Figure 5 As shown. Among them, Figure 5 This is the time-scavenging percentage curve of JPM and SPM1 on DPPH free radicals.

[0138] according to Figure 5 It can be seen that the DPPH scavenging rate of SPM1 is significantly higher than that of JPM, which proves that SPM1 introduced with porous carbon nanospheres in the embodiment of the present application has a strong function of actively scavenging reactive oxygen free radicals.

[0139] 4. Conductivity Characterization

[0140] This application tests the conductivity of JPM, SPM1, and SPM10 in dry and wet states. The experimental process is as follows:

[0141] The conductivity of dry and wet JPM, SPM1 and SPM10 were tested respectively. The results are Figure 6 shown.

[0142] according to Figure 6 It can be seen that when a small amount of porous carbon nanospheres are added to SPM10, the porous carbon nanospheres do not have sufficient density to build a conductive network, and the conductivity of SPM10 and JPM in the dry state cannot be measured. When the carbon density is doubled, the conductivity of SPM1 in the dry state increases significantly. Similarly, the conductivity of SPM1 in the wet state is significantly higher than that of JPM and SPM10, demonstrating that the introduction of porous carbon nanospheres in the examples of this application makes SPM1 have better conductivity, which is expected to "actively" enhance electrical transmission and build a cellular communication network.

[0143] 5. Characterization of Photothermal Effect

[0144] An 808 nm laser was used to irradiate SPM1 or JPM in PBS buffer solution, and the membrane temperature was recorded using an infrared camera. The results were: Figure 7 As shown. Among them, Figure 7 Temperature-time curves of JPM and SPM1 under laser irradiation.

[0145] according to Figure 7 It can be seen that after SPM1 is irradiated with infrared light, the solution temperature increases significantly; while the solution temperature of JPM without the introduction of carbon nanospheres does not change significantly, proving that the introduction of porous carbon nanospheres in the embodiment of the present application enables SPM1 to have a strong photothermal effect, which is expected to actively kill bacteria.

[0146] 6. Characterization of Bone Regeneration Effect in Vivo

[0147] The effect of BC, JPM and SPM1 on the skull osteogenesis of rats was tested. BC was used as the control group, and JPM and SPM1 were used as the experimental groups to test the effect on the skull osteogenesis of rats. Circular bone defects were prepared on the skull of rats, and BC, JPM or SPM1 was placed. After 2 months, the Micro-CT results are shown in Figure 8 Compared with BC, JPM can promote bone defect healing to a certain extent; and the amount of new bone in the SPM1 group is significantly higher than that in the JPM group and the BC group, which proves that the introduction of porous carbon nanospheres with active healing effect further enhances the bone regeneration effect of SPM1.

[0148] Each embodiment in the specification is described in a progressive manner, and the same or similar parts between each embodiment can be referred to each other, and each embodiment focuses on the difference from other embodiments.

[0149] The above examples are only used to illustrate the technical solutions of the present application, and are not limited to the present application; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that they can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the present application.

Claims

1. A method for preparing a porous membrane material with an active healing function, characterized in that: The method comprises the following steps: Providing a polylactic acid solution A, a polycaprolactone solution B, a surfactant solution C, and a carbon material dispersion D; and uniformly mixing the solution A, the solution B, the solution C, and the dispersion D to obtain a mixed solution; The mixed solution is poured onto a bacterial cellulose membrane and cured into a membrane at a temperature of 10 to 40° C. and a relative humidity of 40% to 95%, thereby obtaining a porous membrane material with an active healing function, wherein the porous membrane material has a loose surface with a micron-scale pore structure, a dense surface with a nano-scale pore structure, and a large number of interconnected pore structures. The surfactant is a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer or a polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer; The carbon material is carbon nanospheres; The mass concentration of polylactic acid in solution A is 0.5-5 wt%, the mass concentration of polycaprolactone in solution B is 2-20 wt%, and the mass concentration of surfactant in solution C is 0.5-5 wt%; The mass concentration of the carbon material in the dispersion D is 0.15 to 5 wt %.

2. The preparation method according to claim 1, characterized in that The organic solvents used to form solution A, solution B, solution C and dispersion D are each the same or different and are one of dichloromethane, chloroform, tetrahydrofuran and toluene.

3. The preparation method according to claim 1, characterized in that The molecular weights of the polylactic acid and the polycaprolactone are both 8,000 to 800,000.

4. A porous membrane material with active healing promoting function prepared according to the method according to any one of claims 1 to 3.

5. Use of a porous membrane material with active healing promoting function prepared according to the method of any one of claims 1 to 3 in preparing a bone regeneration barrier membrane.

6. A guided bone regeneration barrier membrane, characterized in that: The porous membrane material with active healing promoting function is prepared by the method according to any one of claims 1 to 3.

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