CN110101901B - Copper silicate hollow microsphere composite fiber scaffold and preparation method and application thereof - Google Patents

Copper silicate hollow microsphere composite fiber scaffold and preparation method and application thereof Download PDF

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CN110101901B
CN110101901B CN201810101997.8A CN201810101997A CN110101901B CN 110101901 B CN110101901 B CN 110101901B CN 201810101997 A CN201810101997 A CN 201810101997A CN 110101901 B CN110101901 B CN 110101901B
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copper silicate
microspheres
drug
composite fiber
hollow microsphere
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吴成铁
余青青
王小成
易正芳
常江
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Zhongke Sifukang Jining Medical Device Technology Co ltd
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Shanghai Institute of Ceramics of CAS
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Abstract

The invention relates to a copper silicate hollow microsphere composite fiber scaffold, a preparation method and application thereof. The copper silicate hollow microsphere composite fiber scaffold comprises: the biological polymer fiber comprises a biological polymer fiber and copper silicate microspheres embedded in the biological polymer fiber, wherein the copper silicate microspheres have a porous structure with a hollow interior and a surrounding nano needle on the outer wall. The copper silicate hollow microsphere composite fiber scaffold not only can effectively kill tumor cells inside and outside a body, but also can promote the healing speed of skin wound surfaces and chronic diabetic wounds caused by surgical removal of tumors.

Description

Copper silicate hollow microsphere composite fiber scaffold and preparation method and application thereof
Technical Field
The invention relates to a copper silicate hollow microsphere composite fiber scaffold, a preparation method and application thereof, in particular to application for treating skin cancer and repairing skin defects, belonging to the field of biological materials.
Background
In recent years, the incidence of various skin cancers has increased year by year, and melanoma, in particular, has a high degree of malignancy, and accounts for a large part of death cases of skin cancer [1 ]. For the treatment of skin cancer, the most common treatment modality currently used clinically is surgical resection [2-4 ]. However, it is difficult to completely remove tumor cells by surgery, and after the lesion tissue is removed by surgery, there is a large skin defect in the tumor site where the body is difficult to self-heal. Therefore, a bifunctional material is needed, which can rapidly remove residual tumor cells and accelerate wound repair.
Prior art documents:
[1]Gladfelter,P.；Darwish,N.H.E.；Mousa,S.A.,Current status and future direction in the management of malignant melanoma.Melanoma Res.2017,27,403-410.
[2]Rosko,A.J.；Vankoevering,K.K.；McLean,S.A.；Johnson,T.M.；Moyer,J.S.,Contemporary Management of Early-Stage Melanoma:A Systematic Review.JAMA Facial Plast.Surg.2017,19,232-238.
[3]Etzkorn,J.R.；Sharkey,J.M.；Grunyk,J.W.；Shin,T.M.；Sobanko,J.F.；Miller,C.J.,Frequency of and Risk Factors for Tumor Upstaging after Wide Local Excision of Primary Cutaneous Melanoma.J.Am.Acad.Dermatol.2017,77,341-348.
[4]Costa Svedman,F.；Spanopoulos,D.；Taylor,A.；Amelio,J.；Hansson,J.,Surgical Outcomes in Patients with Cutaneous Malignant Melanoma in Europe-A Systematic Literature Review.J.Eur.Acad.Dermatol.Venereol.2017,31,603-615.
disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a bifunctional skin tissue engineering material to achieve the dual purposes of removing residual tumor cells and repairing postoperative skin defects.
In a first aspect, the present invention provides a copper silicate hollow microsphere composite fiber scaffold, comprising: the biological polymer fiber comprises a biological polymer fiber and copper silicate microspheres embedded in the biological polymer fiber, wherein the copper silicate microspheres have a porous structure with a hollow interior and a surrounding nano needle on the outer wall.
In the invention, the copper silicate microspheres can be rapidly heated under near infrared light irradiation to show excellent photo-thermal anti-tumor effect, and meanwhile, the porous structure surrounded by the hollow nano needles and the peripheral nano needles in the interior can be used for loading anti-cancer drugs, and the drug release rate is accelerated under the illumination condition, thereby realizing the characteristic of photo-thermal/chemotherapy synergistic anti-tumor. In addition, the copper silicate particles can release therapeutic silicon and copper ions, and have a promoting effect on skin tissue regeneration. Therefore, after the copper silicate microspheres are embedded into the biopolymer fiber scaffold, the fiber scaffold has the double functions of treating tumors and repairing wounds, can effectively kill tumor cells inside and outside the body, and can promote the healing speed of skin wounds and chronic diabetic wounds caused by tumor excision in an operation.
Preferably, the porous structure is loaded with a medicament, and the mass ratio of the medicament to the copper silicate microspheres is preferably 0.05-4.44%.
Preferably, the drug is an anti-cancer drug, preferably an anti-skin cancer drug.
Preferably, the diameter of the copper silicate microspheres is 0.8-1 μm.
Preferably, the diameter of the biopolymer fibers is 0.5 to 2 μm.
Preferably, the mass ratio of the copper silicate microspheres to the biopolymer fibers is 10-30%.
Preferably, the material of the biopolymer fibers is polylactic acid and polycaprolactone.
In a second aspect, the present invention provides a method for preparing the copper silicate hollow microsphere composite fiber scaffold, comprising: and uniformly mixing the copper silicate microspheres and the biopolymer solution, and then carrying out electrostatic spinning to obtain the copper silicate hollow microsphere composite fiber scaffold.
The preparation method has the advantages of simple preparation process, easily controlled conditions, stable performance of the prepared material and the like.
Preferably, the electrostatic spinning speed is 0.01-0.05 mL/min, the voltage is 8-12 kV, the environmental humidity is 50-70% RH, and the distance between the receiving plate and the needle is 15-25 cm.
Preferably, the copper silicate microspheres are loaded with a drug, and the drug-loaded copper silicate microspheres are prepared by soaking the copper silicate microspheres in a drug solution.
Preferably, the copper silicate microspheres are prepared by the following method: carrying out hydrothermal reaction on a mixed aqueous solution containing silicon dioxide microspheres, copper salt and ammonia water at 120-180 ℃ for 10-24 hours, and collecting precipitates to obtain the copper silicate microspheres.
In a third aspect, the invention provides application of the copper silicate hollow microsphere composite fiber scaffold in preparation of a material for treating superficial tumors and repairing soft tissues.
The copper silicate hollow microsphere composite fiber scaffold has dual functions of tumor treatment and wound repair, specifically, in the early stage of skin cancer treatment, the composite fiber scaffold can be rapidly heated under the irradiation of near infrared light, the copper silicate microspheres with the porous structures surrounded by the inner hollow nano needles and the outer wall nano needles can be used for loading anti-cancer drugs, and the release rate of the drugs is accelerated after photo-thermal stimulation, so that the growth of tumors is effectively inhibited by utilizing the synergistic effect of photo-thermal and chemotherapy; in the later treatment period, the fiber scaffold continuously releases therapeutic ions (copper and silicon ions), promotes angiogenesis in the wound area, and obviously improves the healing speed of the skin wound. Therefore, the invention provides a simple and effective scheme for clinical treatment of skin cancer and healing of skin wound, and has good application prospect in the fields of treatment of superficial tumor and soft tissue repair.
Drawings
FIG. 1 shows the elemental surface distribution diagrams of Si, O, Cu, etc. corresponding to the (a) scanning electron microscope, (b, c) transmission electron microscope morphology and (d-g) scanning electron microscope morphology of copper silicate microspheres (CSO HMSs). (ii) drug loading and (i) surface potential of copper silicate microspheres in different concentrations of anticancer drug (trametinib). (j) Photo-thermal heating curve of copper silicate microsphere under different laser power irradiation. The copper silicate microsphere has a porous structure with a hollow interior and a nano-needle aggregation outer wall, and can successfully load anticancer drugs.
FIG. 2 shows the scanning electron microscope morphology of composite electrospun fiber scaffolds with different content of copper silicate microspheres: (a, e) a pure electrospun fiber scaffold (PP); (b, f) a composite electrospun fiber scaffold (10CSO-PP) containing 10% of copper silicate microspheres; (c, g) a composite electrospun fiber scaffold (30CSO-PP) containing 30% of copper silicate microspheres and (d, h) a composite electrospun fiber scaffold (Tra-CSO-PP) containing 30% of drug-loaded copper silicate microspheres.
FIG. 3 composite fiber scaffolds were irradiated with laser (808nm, 0.45W/cm)2) Temperature infrared imaging photograph of (i: PP, II: 10CSO-PP, III: 20CSO-PP, IV: 30CSO-PP, V: Tra-CSO-PP).
FIG. 4 shows the drug release profile of the composite fiber scaffolds at elevated temperatures of 37, 43 and 50 ℃ under near infrared light irradiation. The copper silicate composite fiber support can be rapidly heated under the irradiation of near-infrared laser, and the release of the drug can be effectively regulated and controlled by controlling the laser power. In the figure, NIR represents near-infrared laser irradiation.
FIG. 5 shows (a) survival rate and (b) confocal fluorescence micrographs (red for cytoskeleton and blue for nucleus) of skin cancer cells (murine cutaneous melanoma cells) treated with different fiber scaffolds (PP: pure fiber scaffold; 30 CSO-PP: copper silicate composite fiber scaffold; Tra-CSO-PP: drug-loaded copper silicate fiber composite scaffold) and irradiated with near-infrared laser light at different times (0, 1, 2, 3). (c) Photographs of staining of dead and live cells around different fiber scaffolds with near infrared light (green for live cells and red for dead cells). The Tra-CSO-PP composite fiber scaffold has obvious in-vitro photothermal/chemotherapy synergistic anti-tumor effect. In the figure, Ctr represents a control, Laser represents Laser irradiation. 0Laser means 0 irradiation, 1Laser means 1 irradiation, 2Laser means 2 irradiation, and 3Laser means 3 irradiation.
Figure 6 effects of photothermal/chemotherapy in vivo in combination for tumor treatment and wound repair: (a) photographs of melanoma in nude mice before and after treatment ( days 0, 10 and 14); (b) tumor volume change profile over 14 days; (c) after the treatment is finished, in vitro tumor photos and (d) tumor part skin tissue section staining photos. It can be seen that the in vivo growth of the tumor in the Tra-CSO-PP + laser group is significantly inhibited by the early photothermal/chemotherapy synergistic treatment; meanwhile, the CSO-PP scaffold plays a role in promoting the later-stage skin repair.
Figure 7 in vivo chronic wound repair effect: (a) photographs of skin wounds at different time points ( days 0, 5, 9, 11 and 15); (b) wound healing speed within 15 days.
FIG. 8 photograph of immunofluorescent staining of different scaffolds (left column: green fluorescence for CD 31; blue for cell nuclei) and Masson's Trichrome section staining (middle and right columns).
FIG. 9 quantitative results of gene expression show that the CSO-PP and Tra-CSO-PP scaffolds can promote regeneration of new skin tissue (f), angiogenesis (d, e) and collagen production (type I and type III; g, h).
Detailed Description
The present invention is further described below in conjunction with the following embodiments, which are intended to illustrate and not to limit the present invention.
Disclosed herein is a copper silicate hollow microsphere composite fiber scaffold, comprising: biopolymer fibers and copper silicate microspheres embedded in the biopolymer fibers. Herein, "embedded in a biopolymer fiber" may include being partially embedded within the fiber, and/or being partially exposed outside the fiber, etc.
The biopolymer fibers are fibers formed of a biopolymer. The biological polymer can be polylactic acid, polycaprolactone, polylactic acid-glycolic acid, chitosan and the like. In one example, the biopolymer is comprised of polylactic acid and polycaprolactone. The mass ratio of polycaprolactone to polylactic acid can be 1: (0.5 to 3), for example, 1: 1.
the diameter of the biopolymer fibers can be 0.1-2 μm, and the length can be 10 μm-1 m. The copper silicate hollow microsphere composite fiber scaffold can contain a plurality of biopolymer fibers, and the biopolymer fibers can be regularly or irregularly arranged to form a three-dimensional scaffold.
The copper silicate microsphere has a porous structure with a hollow interior and a nanoneedle surrounded outer wall. The diameter of the copper silicate microspheres can be 0.5-1 μm. The diameter of the inner hollow part can be 300-800 nm.
The porous structure of the copper silicate microspheres can be loaded with drugs. In other words, the copper silicate microspheres embedded in the biopolymer fibers may be drug-loaded copper silicate microspheres (referred to as "drug-loaded copper silicate microspheres"). The drug is preferably an anticancer drug, more preferably an anti-skin cancer drug, such as Trametinib (Trametinib) or the like. The drug loading can be selected according to the requirement, for example, the mass ratio of the drug to the copper silicate microspheres can be 0.05-4.44%, preferably 0.05-1.9%, for example 1.08%.
In the copper silicate hollow microsphere composite fiber scaffold, the mass ratio of the copper silicate microspheres to the biopolymer fibers can be selected according to requirements, and is 10-30% for example. With the increase of the content of the copper silicate microspheres, the photo-thermal effect gradually becomes better. The thickness of the fiber thread is not obviously changed along with the increase of the content of the copper silicate microspheres.
The method for preparing the copper silicate hollow microsphere composite fiber scaffold is characterized in that the copper silicate hollow microsphere is embedded into the biopolymer fibers by utilizing an electrostatic spinning blending method to prepare the copper silicate composite electrostatic spinning fiber scaffold.
Specifically, the copper silicate hollow microsphere composite fiber scaffold is obtained by uniformly mixing copper silicate microspheres and a biopolymer solution and then carrying out electrostatic spinning.
In a preferred embodiment, the copper silicate microspheres are drug-loaded copper silicate microspheres. The drug-loaded copper silicate microspheres can be obtained by soaking copper silicate microspheres in a drug solution. The mass concentration of the copper silicate microspheres in the drug solution can be 40-60 mg/mL, for example 50 mg/mL. In the medicine solution, the concentration of the medicine can be 0.25-4 mg/mL. The soaking temperature may be 0 to 37 ℃, for example, 37 ℃. The soaking time can be 6-48 hours. After soaking, the mixture can be centrifuged, washed, dried and the like. The drug-loading rate can be regulated and controlled by changing the concentration of the drug solution, the drug-loading time and the like.
The copper silicate microspheres have a porous structure surrounded by nanoneedles with a hollow interior and an outer wall as described above. In one example, copper silicate microspheres are synthesized by a silica templating method. Specifically, a mixed aqueous solution containing silicon dioxide microspheres, copper salt and ammonia water is subjected to a hydrothermal process to synthesize copper silicate in situ on the surfaces of the silicon dioxide microspheres, and a silicon dioxide microsphere template is dissolved, so that the copper silicate microspheres with the porous structures, wherein the inner parts of the porous structures are hollow and the outer walls of the porous structures are surrounded by the nano needles.
The particle size of the silica microspheres can be 500nm to 800 nm. The copper salt may be copper nitrate and/or its hydrate (Cu (NO)3)2·3H2O), copper sulfate and/or hydrate thereof (CuSO)4·5H2O). In the mixed aqueous solution, the concentration of the silicon dioxide microspheres can be 0.0025-0.01 g/mL. The concentration of the copper salt in the mixed aqueous solution can be 0.0058-0.02 mol/L. In the mixed aqueous solution, the dosage of ammonia water can be as follows: 0.1-0.2L of ammonia water is used per mole of copper salt. The hydrothermal reaction temperature can be 120-180 ℃. The hydrothermal reaction time can be 10-24 hours.
The solution medium in the biopolymer solution may be a polar solvent such as tetrahydrofuran, N-dimethylformamide, and the like. In one example, the solution medium is composed of tetrahydrofuran and N, N-dimethylformamide, and the volume ratio of the two solvents can be (1-5): 15-20.
In the biopolymer solution, the mass concentration of the biopolymer may be 6 to 25%, for example, 5%.
In the biopolymer solution, the mass concentration of the copper silicate microspheres may be 30% or less, preferably 10 to 30%.
The process parameters of electrospinning may include: the electrostatic spinning speed (liquid flow rate) is 0.01-0.05 mL/min, the voltage is 8-12 kV, the environmental humidity is 50-70% RH, and the distance between the receiving plate and the needle head is 15-25 cm. With this parameter, uniform and continuous diameter fibers can be produced. The electrostatic spinning needle can be 23 gauge and the like.
In a preferred embodiment, a silicon dioxide template method is adopted to synthesize copper silicate microspheres with hollow structures, then anticancer drugs are loaded, and then a drug-loaded copper silicate microsphere is spun into a polylactic acid and polycaprolactone composite fiber scaffold in an electrostatic spinning mode to prepare a drug-loaded copper silicate hollow microsphere composite biopolymer scaffold.
The copper silicate hollow microsphere composite fiber scaffold disclosed herein has multiple functions of good skin tissue regeneration activity, photo-thermal controlled drug release, photo-thermal/chemotherapy synergistic anti-tumor property and the like. Particularly, the particle has controllable photo-thermal performance and a drug slow release function, can be rapidly heated under the irradiation of near-infrared laser, and accelerates the release of drug molecules in the particle, thereby effectively killing tumor cells, inhibiting the growth of tumor tissues, and effectively regulating and controlling the release of the drug by controlling the laser power. The fibrous scaffold can release therapeutic ions (copper and silicon ions) in a body fluid environment, so that angiogenesis in a wound area can be promoted, and the healing speed of a skin wound surface is remarkably improved. Can be used as a tumor treatment and skin regeneration material after clinical surgical excision of skin tumor, provides a simple and effective scheme for the treatment of skin cancer and the healing of skin wound, and has good application prospect in the fields of superficial tumor treatment and tissue repair.
The copper silicate composite biopolymer fiber scaffold disclosed herein has multiple functions of good photothermal/chemotherapy synergistic antitumor, angiogenesis promotion and skin healing acceleration, and has strong practical significance when used as a material for repairing neoplastic tissue defects.
The present invention will be described in detail by way of examples. It is also to be understood that the following examples are illustrative of the present invention and are not to be construed as limiting the scope of the invention, and that certain insubstantial modifications and adaptations of the invention by those skilled in the art may be made in light of the above teachings. The specific process parameters and the like of the following examples are also only one example of suitable ranges, i.e., those skilled in the art can select the appropriate ranges through the description herein, and are not limited to the specific values exemplified below.
Example 1
(1) Mixing absolute ethyl alcohol and ammonia water (the mass fraction is 25-28%) according to the mass ratio of 8:3, stirring in a water bath at 30 ℃ for 1h, quickly pouring (4-5) mL of tetraethoxysilane, continuously stirring for 3h, centrifuging, washing with ethanol and water for several times, and drying in a vacuum oven at 60 ℃ to obtain silicon dioxide spheres with the diameter of 800 nm; mixing 0.13g of silica microspheres and 0.7mmol of Cu (NO)3)2·3H2O and 5mLNH3·H2Adding O into 50mL of deionized water, stirring for half an hour, pouring into a hydrothermal kettle, maintaining the temperature at 140 ℃ for 12 hours, and collecting precipitates to obtain copper silicate microspheres (CSO HMSs) with a porous structure, wherein the porous structure is hollow inside and surrounded by outer wall nano needles. FIG. 1 shows the elemental surface distribution diagrams of Si, O, Cu and the like corresponding to the (a) scanning electron microscope, (b, c) transmission electron microscope morphology and (d-g) scanning electron microscope morphology of the obtained copper silicate microspheres (CSO HMSs). It can be seen that the resulting copper silicate microspheres have a porous structure with a hollow interior and nanoneedles surrounding the outer wall. The diameter of the copper silicate microspheres is 0.8-1 μm. The diameter of the hollow part inside is 500-800 nm.
(2) 0.045g of hollow copper silicate microspheres (CSO HMSs) are weighed and added into 1mL of trametinib dimethyl sulfoxide solution, the concentration of the trametinib is 2mg/mL, and the mixture is placed in a shaking table at 37 ℃ to shake for 24 hours to obtain the drug-loaded copper silicate microspheres (Tra-CSO HMSs). In addition, the concentration of trametinib is respectively 0.25mg/mL, 0.5mg/mL and 1mg/mL, so as to obtain copper silicate microspheres with different drug loading amounts. Fig. 1 shows (h) drug loading and (i) surface potential of copper silicate microspheres in different concentrations of an anticancer drug (trametinib). It can be seen that the greater the concentration of trametinib, the greater the drug loading, and the greater the interfacial potential. FIG. 1 (j) shows copper silicate microspheres (CSO HMSs) at different laser powers (0.45W/cm)2、0.65W/cm2、0.85W/cm2) Photothermal temperature rise curve under irradiation. It can be seen that as the laser power is increased, the temperature of the copper silicate microspheres (CSO HMSs) is increasedThe faster the rise, the higher the temperature rise, indicating that CSO HMSs have very good photothermal properties.
(3) 0.045g of copper silicate particles (CSO HMSs), 0.075g of polylactic acid (PDLLA) and 0.075g of Polycaprolactone (PCL) were mixed and dissolved in 0.3mL of Tetrahydrofuran (THF) and 1.7mL of N, N-Dimethylformamide (DMF), stirred at 30 ℃ for 10 hours, and then charged into a 5mL syringe for electrospinning. The model of the electrostatic spinning needle is 23, the liquid flow rate is 0.03mL/min, the voltage is 10kV, the environmental humidity is 60% RH, and the distance between the receiving plate and the needle is 20 cm. The electrospun fiber scaffolds were collected on aluminum foil paper and dried at room temperature for 24 hours to obtain 30CSO-PP (30% of microspheres of copper silicate).
(4) 0.045g of copper silicate particles (Tra-CSO HMSs) loaded with drugs, 0.075g of polylactic acid (PDLLA) and 0.075g of Polycaprolactone (PCL) were mixed and dissolved in 0.3mL of Tetrahydrofuran (THF) and 1.7mL of N, N-Dimethylformamide (DMF), stirred at 30 ℃ for 10 hours and then loaded into a 5mL syringe for electrospinning. The model of the electrostatic spinning needle is 23, the liquid flow rate is 0.03mL/min, the voltage is 10kV, the environmental humidity is 60% RH, and the distance between the receiving plate and the needle is 20 cm. Collecting the electrostatic spinning fiber scaffold on aluminum foil paper, and drying at room temperature for 24 hours to obtain a Tra-CSO-PP (drug-loaded copper silicate microsphere content of 30%) drug-loaded scaffold.
(5) For comparison, 0.075g of polylactic acid (PDLLA) and 0.075g of Polycaprolactone (PCL) were dissolved in a mixture of 0.3mL of Tetrahydrofuran (THF) and 1.7mL of N, N-Dimethylformamide (DMF), stirred at 30 ℃ for 10 hours, and then charged into a 5mL syringe for electrospinning. The model of the electrostatic spinning needle is 23, the liquid flow rate is 0.03mL/min, the voltage is 10kV, the environmental humidity is 60% RH, and the distance between the receiving plate and the needle is 20 cm. Collecting the electrostatic spinning fiber scaffold on aluminum foil paper, and drying for 24 hours at room temperature to obtain pure electrostatic spinning fiber scaffold (PP).
Example 2
(1) Mixing 0.13g of silica microspheres and 0.7mmol of Cu (NO)3)2·3H2O and 5mLNH3·H2Adding O into 50mL of deionized water, stirring for half an hour, pouring into a hydrothermal kettle, maintaining the temperature at 140 ℃ for 12 hours, collecting the precipitate to obtain the copper silicate microspheres with the porous structure with the hollow interior and the surrounding nano needles on the outer wall(CSO HMSs)。
(2) 0.05g of hollow copper silicate microspheres (CSO HMSs) is weighed and added into 1mL of trametinib dimethyl sulfoxide solution, the concentration of the trametinib is 2mg/mL, and the mixture is placed in a shaking table at 37 ℃ to shake for 24 hours to obtain the drug-loaded copper silicate microspheres (Tra-CSO HMSs).
(3) 0.015g of copper silicate particles (CSO HMSs), 0.075g of polylactic acid (PDLLA) and 0.075g of Polycaprolactone (PCL) are mixed and dissolved in 0.3mL of Tetrahydrofuran (THF) and 1.7mL of N, N-Dimethylformamide (DMF), stirred at 30 ℃ for 10 hours and then loaded into a 5mL syringe for electrostatic spinning. The model of the electrostatic spinning needle is 23, the liquid flow rate is 0.03mL/min, the voltage is 10kV, the environmental humidity is 60% RH, and the distance between the receiving plate and the needle is 20 cm. The electrospun fiber scaffolds were collected on aluminum foil paper and dried at room temperature for 24 hours to obtain 10CSO-PP (copper silicate microsphere content of 10%) scaffolds.
Example 3
(1) Mixing 0.13g of silica microspheres and 0.7mmol of Cu (NO)3)2·3H2O and 5mLNH3·H2Adding O into 50mL of deionized water, stirring for half an hour, pouring into a hydrothermal kettle, maintaining the temperature at 140 ℃ for 12 hours, and collecting precipitates to obtain copper silicate microspheres (CSO HMSs) with a porous structure, wherein the porous structure is hollow inside and surrounded by outer wall nanoneedles.
(2) 0.05g of hollow copper silicate microspheres (CSO HMSs) is weighed and added into 1mL of trametinib dimethyl sulfoxide solution, the concentration of the trametinib is 2mg/mL, and the mixture is placed in a shaking table at 37 ℃ to shake for 24 hours to obtain the drug-loaded copper silicate microspheres (Tra-CSO HMSs).
(3) 0.030g of copper silicate particles (CSO HMSs), 0.075g of polylactic acid (PDLLA) and 0.075g of Polycaprolactone (PCL) were mixed and dissolved in 0.3mL of Tetrahydrofuran (THF) and 1.7mL of N, N-Dimethylformamide (DMF), stirred at 30 ℃ for 10 hours, and then charged into a 5mL syringe for electrospinning. The model of the electrostatic spinning needle is 23, the liquid flow rate is 0.03mL/min, the voltage is 10kV, the environmental humidity is 60% RH, and the distance between the receiving plate and the needle is 20 cm. The electrospun fiber scaffolds were collected on aluminum foil paper and dried at room temperature for 24 hours to obtain 20CSO-PP (copper silicate microsphere content of 20%) scaffolds.
FIG. 2 shows the scanning electron microscope morphologies of composite fiber scaffolds with different copper silicate microsphere contents: (a, e) a pure electrospun fiber scaffold (PP); (b, f) a composite electrospun fiber scaffold (10CSO-PP) containing 10% of copper silicate microspheres; (c, g) a composite electrospun fiber scaffold (30CSO-PP) containing 30% of copper silicate microspheres and (d, h) a composite electrospun fiber scaffold (Tra-CSO-PP) containing 30% of drug-loaded copper silicate microspheres. It can be seen that the copper silicate microspheres are partially embedded inside the fiber thread and partially exposed outside the thread, and the thickness of the fiber thread does not change significantly as the content of the copper silicate microspheres increases.
Evaluation of efficacy of photothermal-promoted drug release of copper silicate hollow microsphere composite fiber scaffold
The resulting scaffolds were soaked in 1mL of phosphate buffer, the scaffolds were irradiated with 808nm near-infrared light, and the temperature change was monitored in real time using a thermal imager. FIG. 3 shows a composite fiber scaffold under laser irradiation (808nm, 0.45W/cm)2) Temperature infrared imaging photograph of (i: PP, II: 10CSO-PP, III: 20CSO-PP, IV: 30CSO-PP, V: Tra-CSO-PP), fig. 4 shows the drug release curves of the drug-loaded fiber scaffold Tra-CSO-PP obtained in example 1 when heated to 37, 43 and 50 ℃ under near infrared light irradiation. It can be seen that the temperature of the drug-loaded fiber support is obviously increased in a very short time, and the drug-loaded fiber support has good photo-thermal performance. The photo-thermal performance of the drug-loaded fiber scaffold can be regulated and controlled by changing the content of copper silicate, laser power and the like. The laser power was adjusted to raise the temperature of the surface of the fibrous scaffold to 37, 43 and 50 c, it was found that the higher the temperature, the faster the drug release rate, and that controlled release of the drug could be achieved by turning the laser on and off.
Evaluation of in vitro anti-tumor capacity of copper silicate hollow microsphere composite fiber scaffold
The PP, 30CSO-PP and Tra-CSO-PP fiber scaffolds were placed on top of skin melanoma cells and the scaffolds were irradiated with 808nm near infrared light for 15 minutes. After the cells are subjected to fluorescent staining, the cell density and survival condition of the cells before and after illumination are observed by using a confocal electron microscope, and the change of the survival rate of the cells is detected by using a CCK8 method.
FIG. 5 shows (a) survival rate and (b) confocal fluorescence microscope photographs of skin cancer cells (murine skin melanoma cells) after different numbers (0, 1, 2, 3) of treatments and near-infrared laser irradiation with different fiber scaffolds (PP: pure fiber scaffold; 30 CSO-PP: copper silicate composite fiber scaffold; Tra-CSO-PP: drug-loaded copper silicate fiber composite scaffold), (c) staining photographs of dead and live cells around different fiber scaffolds by near-infrared light irradiation. As can be seen from FIG. 3, most of the tumor cells were dead and significantly decreased in number after the irradiation of light in the 30CSO-PP and Tra-CSO-PP fiber scaffold groups, wherein the Tra-CSO-PP fiber scaffold had the best antitumor effect, and the number of cells before and after the irradiation of light in the PP scaffold group was not significantly changed. The copper silicate particles are embedded into the fiber scaffold, so that the scaffold has excellent photo-thermal anti-tumor performance, and the fiber scaffold has the photo-thermal/chemotherapy synergistic anti-tumor characteristic due to the composite action of the drug-loaded copper silicate particles.
Evaluation of in vivo antitumor effect of copper silicate hollow microsphere composite fiber scaffold
Constructing a skin melanoma wound model of a nude mouse, after a tumor grows to a certain size, making a 10mm wound above the tumor, pasting PP, 30CSO-PP and Tra-CSO-PP scaffolds with the diameter of 10mm, and carrying out continuous photo-thermal treatment for 3-4 days by using near infrared. The change in tumor volume was recorded over two weeks, and tumor tissue and surrounding skin tissue were removed for analysis after treatment.
Figure 6 shows the effect of photothermal/chemotherapy in vivo in synergistic tumor treatment and wound repair: (a) photographs of melanoma in nude mice before and after treatment ( days 0, 10 and 14); (b) tumor volume change profile over 14 days; (c) after the treatment is finished, in vitro tumor photos and (d) tumor part skin tissue section staining photos. As can be seen from FIG. 4, the tumor growth in the Tra-CSO-PP + laser group was significantly inhibited by the early photothermal/chemotherapeutic combination treatment; meanwhile, the 30CSO-PP scaffold plays a role in promoting the later-stage skin repair. The results show that the tumors of the 30CSO-PP and Tra-CSO-PP scaffold group do not relapse within two weeks after early treatment, the wounds are gradually healed under the action of the composite membrane, normal skin tissues are regenerated, and the composite fiber scaffold has double functions of resisting tumors and repairing skin tissue defects on the same animal model.
Evaluation of in vitro tissue regeneration efficacy of copper silicate hollow microsphere composite fiber scaffold
Normal skin cells (skin fibroblasts and vascular endothelial cells) are inoculated on the surface of the fibrous scaffold, the appearance of the cells is observed by a scanning electron microscope, and the proliferation capacity of the cells is detected by a CCK8 method for 1, 3 and 7 days. The gene expression of human umbilical vein endothelial cells on the composite scaffold was tested by RT-PCR.
Evaluation of skin repair performance of copper silicate hollow microsphere composite fiber scaffold in animal body
A diabetic chronic wound model is constructed, PP, 30CSO-PP and Tra-CSO-PP are implanted into a wound position, and skin wound pictures and wound healing speed are observed at different time points.
Fig. 7 shows the in vivo chronic wound repair effect: (a) photographs of skin wounds at different time points ( days 0, 5, 9, 11 and 15); (b) wound healing speed within 15 days. FIG. 8 shows a photograph of immunofluorescent staining (left column: CD31 and nuclear staining) and staining of Masson's trichrome histological sections (middle and right columns). FIG. 9 shows gene expression quantification, and the results indicate that 30CSO-PP and Tra-CSO-PP scaffolds can promote regeneration of neogenetic skin tissue (f), angiogenesis (d, e), and collagen production (type I and type III; g, h). The results show that the copper silicate hollow microsphere composite fiber scaffold supports cell adhesion and can promote the proliferation of skin cells and the differentiation of blood vessels. In the diabetic chronic wound repair experiment for 15 days, the 30CSO-PP and Tra-CSO-PP composite bracket obviously accelerates the healing speed of the wound and promotes the regeneration of blood vessels and the deposition of collagen at the newly born skin.
From the evaluation results, the copper silicate hollow microsphere composite fiber scaffold is expected to be used as a multifunctional implant material for treating tumors and repairing tissue defects for clinical application.

Claims (12)

1. A copper silicate hollow microsphere composite fiber scaffold, comprising: the biological polymer fiber comprises a biological polymer fiber and copper silicate microspheres embedded in the biological polymer fiber, wherein the copper silicate microspheres have a porous structure with a hollow interior and a surrounding nano needle on the outer wall.
2. The copper silicate hollow microsphere composite fiber scaffold according to claim 1, wherein a drug is loaded in said porous structure.
3. The copper silicate hollow microsphere composite fiber scaffold as claimed in claim 2, wherein the mass ratio of the drug to the copper silicate microspheres is 0.05-4.44%.
4. The copper silicate hollow microsphere composite fiber scaffold according to claim 2, wherein said drug is an anticancer drug.
5. The copper silicate hollow microsphere composite fiber scaffold according to claim 4, wherein said drug is an anti-skin cancer drug.
6. The copper silicate hollow microsphere composite fiber scaffold as claimed in claim 1, wherein the diameter of said copper silicate microspheres is 0.8-1 μm, the diameter of said biopolymer fibers is 0.5-2 μm, and the mass ratio of said copper silicate microspheres to said biopolymer fibers is 10-30%.
7. The copper silicate hollow microsphere composite fiber scaffold as claimed in claim 1, wherein the material of said biopolymer fibers is polylactic acid and polycaprolactone.
8. The method for preparing the copper silicate hollow microsphere composite fiber scaffold as claimed in any one of claims 1 to 7, wherein the copper silicate hollow microsphere composite fiber scaffold is obtained by uniformly mixing copper silicate microspheres and a biopolymer solution and then performing electrostatic spinning.
9. The method according to claim 8, wherein the electrospinning speed is 0.01 to 0.05mL/min, the voltage is 8 to 12kV, the ambient humidity is 50 to 70% RH, and the distance between the receiving plate and the needle is 15 to 25 cm.
10. The method of claim 8, wherein the copper silicate microspheres are loaded with a drug, and the drug-loaded copper silicate microspheres are prepared by soaking the copper silicate microspheres in a drug solution.
11. The method of claim 8, wherein the copper silicate microspheres are prepared by: carrying out hydrothermal reaction on a mixed aqueous solution containing silicon dioxide microspheres, copper salt and ammonia water at 120-180 ℃ for 10-24 hours, and collecting precipitates to obtain the copper silicate microspheres.
12. Use of the hollow microsphere composite fiber scaffold of copper silicate according to any one of claims 1 to 7 for preparing a material for treating superficial tumors and repairing soft tissues.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008145361A1 (en) * 2007-06-01 2008-12-04 The Jordanian Pharmaceutical Manufacturing Co. Mineral-fiber solid dispersion, method for preparing the same, and use thereof as pharmaceutical tableting aid

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008145361A1 (en) * 2007-06-01 2008-12-04 The Jordanian Pharmaceutical Manufacturing Co. Mineral-fiber solid dispersion, method for preparing the same, and use thereof as pharmaceutical tableting aid

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
《A Smart Hyperthermia Nanofiber with Switchable Drug Release for Inducing Cancer Apoptosis》;Young‐Jin Kim;《Advanced Functional Materials》;20130614;5753–5761 *
《Facile Synthesis and Properties of Hierarchical Double-Walled Copper Silicate Hollow Nanofibers Assembled by Nanotubes》;Renxi Jin 等;《ACS Nano》;20140311;第8卷(第4期);3664–3670 *
《Hierarchically micro-patterned nanofibrous scaffolds with a nanosized bio-glass surface for accelerating wound healing》;He Xu 等;《Nanoscale》;20151009;18446–18452 *
《Mesoporous silica-based versatile theranostic nanoplatform constructed by layer-by-layer assembly for excellent photodynamic/chemo therapy》;Wei-Hai Chen等;《Biomaterials》;20170228;54-65 *
《Topological Transformations of Core–Shell Precursors to Hierarchically Hollow Assemblages of Copper Silicate Nanotubes》;Guowu Zhan and Hua Chun Zeng;《ACS Appl. Mater. Interfaces》;20171003;第9卷(第42期);37210–37218 *
《Ultrasmall CuCo2S4 Nanocrystals: All-in-One Theragnosis Nanoplatform with Magnetic Resonance/Near-Infrared Imaging for Efficiently Photothermal Therapy of Tumors》;Bo Li 等;《Advanced Functional Materials》;20170123;1606218（1-10） *

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