CN110420350B - Adhesive temperature-sensitive hydrogel of composite bioglass and preparation method and application thereof - Google Patents

Adhesive temperature-sensitive hydrogel of composite bioglass and preparation method and application thereof Download PDF

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CN110420350B
CN110420350B CN201910803050.6A CN201910803050A CN110420350B CN 110420350 B CN110420350 B CN 110420350B CN 201910803050 A CN201910803050 A CN 201910803050A CN 110420350 B CN110420350 B CN 110420350B
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bioglass
composite
sensitive hydrogel
adhesive temperature
temperature
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CN110420350A (en
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赵晓丽
郑志强
潘浩波
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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Abstract

The embodiment of the invention provides an adhesive temperature-sensitive hydrogel for composite bioglass, which comprises the following components in percentage by weight: 25-40% of PDLLA-PEG-PDLLA triblock polymer, 1-1.25% of dopamine modified quaternized chitosan, 1-5% of bioglass and the balance of deionized water. The adhesive temperature-sensitive hydrogel of the composite bioglass has good adhesiveness, antibacterial property and biocompatibility. The adhesive temperature-sensitive hydrogel of the composite bioglass can be self-adhered to the surface of skin wound, and is favorable for promoting skin regeneration and wound repair. The invention also provides a preparation method and application of the adhesive temperature-sensitive hydrogel of the composite bioglass. The preparation method has simple process and high yield, is suitable for large-scale industrial production, and the adhesive temperature-sensitive hydrogel of the composite bioglass prepared by the preparation method has good adhesiveness, antibacterial property and biocompatibility, and has wide application prospect in preparation of medicines for healing skin wounds.

Description

Adhesive temperature-sensitive hydrogel of composite bioglass and preparation method and application thereof
Technical Field
The invention relates to the technical field of biomedical materials, in particular to an adhesive temperature-sensitive hydrogel of composite bioglass, and a preparation method and application thereof.
Background
The skin is the largest organ of the human body and is easily damaged due to the large area of the skin exposed to the external environment. Traditional skin wound dressings have gauze, bandages and the like, but all have certain limitations, can not accelerate wound healing, completely meet the requirements of chronic wound healing, and can be adhered with wound secretions to easily cause secondary injury during dressing change. However, many hydrogel dressing products developed in recent years have excellent soft and wet characteristics and biocompatibility, and can improve wound healing and repair skin to some extent, but most products have poor tissue adhesion and antibacterial performance. For example, some hydrogel products with low tissue adhesion can fill irregular wounds at the beginning of application, but due to their poor mechanical properties and poor adhesion, they are prone to flow away under external forces, which is not conducive to wound healing. The traditional method of enhancing the antibacterial performance of hydrogel products by adding antibiotics, antibacterial peptides or antibacterial drugs containing nano Ag and the like is often accompanied with certain toxic and side effects.
Therefore, the development of hydrogel dressing products with good adhesiveness, antibacterial property and biocompatibility is of great significance.
Disclosure of Invention
In view of this, the embodiment of the invention provides an adhesive temperature-sensitive hydrogel of composite bioglass, and a preparation method and application thereof. The adhesive temperature-sensitive hydrogel of the composite bioglass can be self-adhered to the surface of skin wound, and is favorable for promoting skin regeneration and wound repair.
In a first aspect, the invention provides an adhesive temperature-sensitive hydrogel for composite bioglass, which comprises the following components in percentage by weight: 25-40% of PDLLA-PEG-PDLLA (racemic polylactic acid-polyethylene glycol-racemic polylactic acid, PLEL) triblock polymer, 1-1.25% of dopamine modified quaternized chitosan, 1-5% of bioglass and the balance of deionized water.
Optionally, in the adhesive temperature-sensitive hydrogel of the composite bioglass, the weight percentage of the PDLLA-PEG-PDLLA triblock polymer is 30-40%.
Optionally, in the adhesive temperature-sensitive hydrogel of the composite bioglass, the weight percentage of the PDLLA-PEG-PDLLA triblock polymer is 25-35%.
Optionally, in the adhesive temperature-sensitive hydrogel of the composite bioglass, the weight percentage of the PDLLA-PEG-PDLLA triblock polymer is 30-40%.
Optionally, in the adhesive temperature-sensitive hydrogel of the composite bioglass, the weight percentage of the PDLLA-PEG-PDLLA triblock polymer is 35-40%.
In one embodiment of the present invention, the weight percentage of the PDLLA-PEG-PDLLA triblock polymer may be 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, or 40%.
In a specific embodiment of the present invention, in the adhesive temperature-sensitive hydrogel of composite bioglass, the weight percentage of the dopamine-modified quaternized chitosan may be 1%, 1.02%, 1.04%, 1.06%, 1.08%, 1.10%, 1.12%, 1.14%, 1.16%, 1.18%, 1.20%, 1.22%, 1.24% or 1.25%.
Optionally, in the adhesive temperature-sensitive hydrogel of the composite bioglass, the weight percentage of the bioglass is 1-3%.
Optionally, in the adhesive temperature-sensitive hydrogel of the composite bioglass, the weight percentage of the bioglass is 3-5%.
In a specific embodiment of the present invention, in the adhering temperature-sensitive hydrogel of composite bioglass, the weight percentage of bioglass may be 1%, 2%, 3%, 4% or 5%.
Optionally, the shape of the bioglass is spherical or spheroidal, and the particle size of the bioglass is 600-800 nm.
Optionally, the particle size of the bioglass is 650-800 nm.
Optionally, the particle size of the bioglass is 600-700 nm.
Optionally, the particle size of the bioglass is 700-800 nm.
In a specific embodiment of the present invention, the particle size of the bioglass can be, but is not limited to, 600nm, 620nm, 650nm, 680nm, 700nm, 720nm, 750nm, 780nm, 800 nm.
The bioglass is nano-scale, can prevent the problem of sedimentation in the temperature-sensitive adhesive hydrogel of the composite bioglass caused by overlarge particle size, and is beneficial to improving the uniformity of each component of the temperature-sensitive adhesive hydrogel of the composite bioglass; meanwhile, the nano-scale bioglass has high specific surface area, so that the effect of the bioglass on promoting vascularization of endothelial cells and improving release of related vascular growth factors is further improved; the wound repair effect of the temperature-sensitive adhesive hydrogel of the composite bioglass is improved. Optionally, the bioglass disclosed by the invention can also participate in the preparation of other composite materials for wound repair.
Alternatively, the constituent components of the bioglass may include, but are not limited to, silica, calcium oxide, and phosphorus pentoxide.
Optionally, the bioglass comprises silicon dioxide, calcium oxide and phosphorus pentoxide.
Optionally, in one embodiment of the present invention, the bioglass comprises silica, calcium oxide, and phosphorus pentoxide.
Optionally, the bioglass comprises the following components in percentage by mass: 80% silica, 16% calcium oxide and 4% phosphorus pentoxide.
Alternatively, the molecular weight of the PDLLA-PEG-PDLLA triblock polymer is 4500-.
Optionally, in the dopamine-modified quaternized chitosan, the grafting rate of dopamine is 6-7%.
Optionally, the temperature range of 35-70 ℃ of the temperature-sensitive adhesive hydrogel of the composite bioglass is gelatinous.
In the invention, the temperature range of 35-70 ℃ of the adhesive temperature-sensitive hydrogel of the composite bioglass is gelatinous, and when the temperature is lower than 35 ℃, the adhesive temperature-sensitive hydrogel of the composite bioglass is liquid. When the adhesive temperature-sensitive hydrogel of the composite bioglass is coated on the skin surface of mammals including human beings, the adhesive temperature-sensitive hydrogel of the composite bioglass is in a gel shape at the body temperature of 35-37 ℃, and can be adhered on the skin surface by self adhesion.
Optionally, the pH of the adhesive temperature-sensitive hydrogel of the composite bioglass is 5.0-7.0.
Optionally, the pH of the adhesive temperature-sensitive hydrogel of the composite bioglass is 5.5-7.0.
Optionally, the pH of the adhesive temperature-sensitive hydrogel of the composite bioglass is 6.0-7.0.
Optionally, the pH of the adhesive temperature-sensitive hydrogel of the composite bioglass is 6.5-7.0.
Optionally, the pH of the adhesive temperature-sensitive hydrogel of the composite bioglass is 5.5-6.0.
In a specific embodiment of the present invention, the pH of the adhesive temperature-sensitive hydrogel of the composite bioglass is 5.0, or 5.5, or 60, or 6.5, or 7.0.
In a second aspect, the invention provides a preparation method of an adhesive temperature-sensitive hydrogel of composite bioglass, which comprises the following steps:
adding 2, 3-epoxypropyltrimethylammonium chloride (GMTAC) into an acidic solution of Chitosan (CS) to realize quaternization of the chitosan, and then collecting to obtain Quaternized Chitosan (QCS); preparing an aqueous solution of the quaternized chitosan, adding dopamine hydrochloride to perform a coupling reaction, and after the reaction is finished, purifying and drying the solution to obtain dopamine modified quaternized chitosan (QCS-C);
adding the dopamine modified quaternized chitosan and bioglass into an aqueous solution of a PDLLA-PEG-PDLLA triblock polymer, and uniformly stirring to obtain the adhesive temperature-sensitive hydrogel of the composite bioglass, wherein the mass fraction of the PDLLA-PEG-PDLLA triblock polymer is 25-40%, the mass fraction of the dopamine modified quaternized chitosan is 1-1.25%, and the mass fraction of the bioglass is 1-5%.
Optionally, the specific preparation process of the quaternized chitosan comprises: adding aqueous solution of 2, 3-epoxypropyltrimethylammonium chloride into acidic solution of chitosan with the mass fraction of 1-1.5%, stirring and reacting for 15-20h at 50-60 ℃, and after the reaction is finished, dialyzing, freezing and drying to obtain the quaternized chitosan.
Alternatively, the 2, 3-epoxypropyltrimethylammonium chloride may be added slowly. For example, when the reaction system is relatively small, the 2, 3-epoxypropyltrimethylammonium chloride is added dropwise. By slowly adding 2, 3-epoxypropyl trimethyl ammonium chloride into the acidic solution of chitosan, the two can react more fully, and the quaternized chitosan with higher conversion rate can be obtained.
Optionally, the pH of the aqueous solution of the quaternized chitosan is 4.5-5.5, the reaction temperature of the coupling reaction is 0-4 ℃, and the reaction time is 10-16 h.
In the invention, the pH value of the aqueous solution of the quaternized chitosan is adjusted to 4.5-5.5, so that the dopamine can be prevented from being oxidized under alkaline conditions. Optionally, the pH of the aqueous solution of quaternized chitosan is adjusted using a hydrochloric acid solution.
Alternatively, the molar ratio of the 2, 3-epoxypropyltrimethylammonium chloride to the amino groups on the chitosan is (1.5-1.6): 1.
optionally, the molar ratio of the dopamine hydrochloride to the quaternized chitosan is (1.2-1.8): 1.
optionally, the dopamine-modified quaternized chitosan is obtained by a dialysis purification process, and then is collected after freeze-drying.
Optionally, the dialysis purification process comprises: and sequentially placing the dopamine modified quaternized chitosan into a hydrochloric acid solution with the pH value of 4.0-5.0 and deionized water, and then dialyzing through a dialysis bag. In the invention, the dialysis purification operation can effectively remove unreacted raw materials and byproducts in the coupling reaction of the quaternized chitosan and the dopamine hydrochloride.
The dopamine modified quaternized chitosan is a chitosan derivative obtained by modifying one amino group and two hydroxyl groups on a chitosan constitutional unit, and the bioactivity and the water solubility of the dopamine modified quaternized chitosan can be greatly improved. In the dopamine modified quaternized chitosan, the antibacterial performance of the quaternized grafted chitosan is also obviously superior to that of common chitosan or other chitosan derivatives.
In the preparation method, the optimized mass fraction of the dopamine modified quaternized chitosan plays an important role in uniformly dispersing all components of the adhesive temperature-sensitive hydrogel of the composite bioglass, and the mass fraction of the dopamine modified quaternized chitosan is beneficial to improving the antibacterial property and the adhesive property of the product to a certain extent. For example, the catechol group in dopamine groups has a very strong affinity for organic and inorganic surfaces. When the mass fraction of the dopamine-modified quaternized chitosan is too high, the dopamine-modified quaternized chitosan cannot be completely dissolved and dispersed in the adhesive temperature-sensitive hydrogel system of the composite bioglass.
Optionally, the method for preparing the bioglass comprises: adding ethyl orthosilicate, triethyl phosphate and calcium nitrate tetrahydrate into an ethanol solution in which lauryl amine is dissolved, and stirring for 2-4 hours at the temperature of 30-40 ℃ to obtain a sol solution; then collecting the white precipitate in the sol solution, washing, drying in vacuum, transferring to a high-temperature calcining device, heating to 600-; the composition of the bioglass comprises silicon dioxide, calcium oxide and phosphorus pentoxide.
Optionally, the mole fraction of the constituent components of the bioglass is: 80% silica, 16% calcium oxide and 4% phosphorus pentoxide.
Optionally, the volume ratio of the absolute ethyl alcohol to the deionized water in the ethyl alcohol solution is (2.5-3.5): 1.
optionally, the molar concentration of dodecylamine is 0.17 to 0.20M.
Optionally, the shape of the bioglass is spherical or spheroidal, and the particle size of the bioglass is 600-800 nm.
The regular spherical or spheroidal bioglass has larger specific surface area and better dispersibility.
In a third aspect, the invention further provides an application of the adhesive temperature-sensitive hydrogel of the composite bioglass according to the first aspect of the invention or the adhesive temperature-sensitive hydrogel of the composite bioglass prepared by the preparation method according to the second aspect of the invention in preparation of a medicament for healing skin wounds.
The adhesive temperature-sensitive hydrogel of the composite bioglass can generate sol-gel transformation through temperature change, and the moderate gelation condition can maintain the biological activity of target cells or medicines to the maximum extent; therefore, the adhesive temperature-sensitive hydrogel of the composite bioglass has important application prospect in the field of wound dressing materials.
Optionally, the adhesive temperature-sensitive hydrogel of the composite bioglass can be used as a drug carrier without limitation, and is beneficial to controlling drug release. For example, the adhesive temperature-sensitive hydrogel of the composite bioglass can be used as a dressing loaded with an agent for treating skin wounds, such as an anti-inflammatory agent, a growth-promoting agent, a hemostatic agent, and the like.
The beneficial effects of the invention include:
(1) the temperature-sensitive hydrogel of the composite bioglass is prepared by taking temperature-sensitive hydrogel of PDLLA-PEG-PDLLA triblock polymer as a matrix, and the inside of the temperature-sensitive hydrogel contains dopamine-modified quaternary ammonium salt chitosan and bioglass, so that the temperature-sensitive hydrogel is high in homogenization degree and stable in property; the adhesive temperature-sensitive hydrogel of the composite bioglass has strong adhesive force, not only can enhance the adhesiveness through the quaternary ammonium salt group with positive charge on the dopamine modified quaternary ammonium salt chitosan chain segment, but also can enhance the adhesiveness through the cross-linking action of the quinoid structure formed by partial oxidation of dopamine and the amino on the surface of skin tissue; the adhesive temperature-sensitive hydrogel of the composite bioglass also has excellent antibacterial property and biocompatibility.
(2) The adhesive temperature-sensitive hydrogel of the composite bioglass is in a flowing state at normal temperature and in a gel state at the body temperature of 35-37 ℃, and can be injected to a wound surface to form a hydrogel dressing closely attached to skin tissues so as to maintain the wettability and antibacterial property of the wound part. Compared with the traditional micron-sized bioactive glass, the bioglass is more favorable for homogenization of hydrogel and avoids the condition of overhigh alkalinity of local wound surfaces, and the PDLLA-PEG-PDLLA triblock polymer and the dopamine-modified quaternary ammonium chitosan in the temperature-sensitive adhesive hydrogel of the composite bioglass are weakly acidic after being degraded, so that the bioglass is favorable for repairing and reconstructing wound surface skins.
(3) The preparation method of the adhesive temperature-sensitive hydrogel of the composite bioglass has simple process and high yield, and is suitable for large-scale industrial production, and the adhesive temperature-sensitive hydrogel of the composite bioglass prepared by the preparation method has good adhesiveness, antibacterial property and biocompatibility, and has wide application prospect in preparing medicines for skin wound healing dressings; the adhesive temperature-sensitive hydrogel of the composite bioglass can also be used as a good drug carrier, and is beneficial to controlling drug release.
Advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of embodiments of the invention.
Drawings
In order to more clearly illustrate the contents of the present invention, a detailed description thereof will be given below with reference to the accompanying drawings and specific embodiments.
FIG. 1 is a scanning electron microscope image of a bioglass provided in accordance with an embodiment of the present invention;
FIG. 2 is a scanning electron micrograph of a bioglass provided in accordance with another embodiment of the present invention;
FIG. 3 is a nuclear magnetic characterization spectrum of dopamine-modified quaternary ammonium chitosan in an adhesive temperature-sensitive hydrogel of a composite bioglass provided in an embodiment of the present invention;
FIG. 4 is a diagram illustrating a temperature-sensitive transition rheology of an adhesive temperature-sensitive hydrogel of a composite bioglass according to an embodiment of the present invention;
fig. 5 is a graph illustrating the cytotoxicity of the leaching solution of the adhesion temperature-sensitive hydrogel of the composite bioglass with different concentrations on murine fibroblasts according to an embodiment of the present invention.
Detailed Description
While the following is a description of the preferred embodiments of the present invention, it should be noted that those skilled in the art can make various modifications and improvements without departing from the principle of the embodiments of the present invention, and such modifications and improvements are considered to be within the scope of the embodiments of the present invention.
The terms "comprising" and "having," and any variations thereof, as appearing in the specification, claims and drawings of this application, are intended to cover non-exclusive inclusions. For example, a process, method, system, article, or apparatus that comprises a list of steps or elements is not limited to only those steps or elements listed, but may alternatively include other steps or elements not listed, or inherent to such process, method, article, or apparatus.
Unless otherwise specified, the raw materials and other chemicals used in the examples of the present invention are commercially available.
Example 1
A method for preparing bioglass, comprising:
SiO in bioglass2:CaO:P2O5The molar ratio was 80:16: 4. The volume ratio is 16: 5, 125mL of absolute ethyl alcohol/water mixed solution is used as a solvent, 4g of dodecylamine is added and stirred until the solution is completely dissolved, then 16mL of ethyl orthosilicate and 1.22mL of triethyl phosphate are added dropwise, finally 3.39g of calcium nitrate tetrahydrate are added, and magnetic stirring is carried out for 3 hours at 35 ℃ to obtain the bioglass sol. Collecting white precipitate, alternately washing with anhydrous ethanol and deionized water for 3 times, and vacuum drying to obtain white block; then transferring the white block into a crucible for high-temperature calcination, and maintaining the temperature to 650 ℃ at the heating rate of 2 ℃/min for 3 hours; and after high-temperature calcination treatment, naturally cooling to obtain powdery white powder, namely the rice bioactive glass.
The bioglass prepared in the above examples was characterized by its spherical or spheroidal shape, as shown in fig. 1 and 2. And the particle size of the bioglass is nano-scale and uniform, and the particle size is about 600-800 nm.
Because the bioglass (or bioactive glass) is a ceramic material with bioactivity, the bioglass (or bioactive glass) has optimistic application prospect in the field of bone tissue repair, Si, Ca ions and the like released by the bioglass in a solution can promote vascularization of endothelial cells and improve expression of related vascular growth factors, such as vascular endothelial growth factors and basic fibroblast growth factors, so that wound repair is promoted. The bioglass prepared by the preparation method provided by the embodiment of the invention is nano-scale, and has the advantages of uniform size, large specific surface area, high chemical activity and the like. The bioglass can be uniformly dispersed in the adhesive temperature-sensitive hydrogel of the composite bioglass, and the distribution of all components in the adhesive temperature-sensitive hydrogel of the composite bioglass is promoted to be more uniform. The nano-scale bioglass has high specific surface area, and is beneficial to further improving the effect of the bioglass in promoting the vascularization of endothelial cells and improving the release of related blood vessel growth factors; the wound repair effect of the temperature-sensitive adhesive hydrogel of the composite bioglass is improved.
Example 2
A preparation method of an adhesive temperature-sensitive hydrogel of composite bioglass comprises the following steps:
at normal temperature, Chitosan (CS) (purchased from Sigma-Aldrich, product number: 448877) is dissolved in 87.5mmol/L acetic acid solution, the mixture is magnetically stirred for 12h at room temperature to obtain 1-1.5 wt% of CS solution, and then 1.16mL of 2, 3-epoxypropyltrimethylammonium chloride (GMTAC) (9.25-9.30 mmol/L) aqueous solution is added in 1h, wherein the molar weight of GMTAC is 1.5-1.6 times of that of amino groups on the chitosan. Stirring and reacting for 18h at 55 ℃, dialyzing and freeze-drying after the reaction is finished to obtain the Quaternized Chitosan (QCS). Through detection, the yield of the QCS is more than 80%, and the nuclear magnetic representation that the grafting rate can reach 45-47%;
stirring and dissolving the prepared QCS in an aqueous solution at normal temperature to obtain a QCS aqueous solution with the concentration of about 0.12g/mL, adjusting the pH value to 5.0 by using a 2M HCl solution, adding dopamine hydrochloride, and fully stirring and dissolving the dopamine hydrochloride, wherein the molar ratio of the dopamine hydrochloride to the quaternized chitosan is 1.5: 1; coupling reaction at 0-4 deg.c for 12 hr while maintaining pH 5.0; after the reaction is finished, putting the mixture into HCl solution with the pH value of 5.0 and deionized water for dialysis in sequence, and then freeze-drying the mixture to obtain the dopamine modified quaternized chitosan (QCS-C); wherein the yield of QCS-C is more than 80 percent, and the grafting rate of dopamine is about 6 to 7 percent.
Preparing 30 wt% of PDLLA-PEG-PDLLA triblock polymer aqueous solution, and sequentially adding 1 wt% of QCS-C and 2 wt% of bioglass; and (3) fully and uniformly stirring to obtain the adhesive temperature-sensitive hydrogel (PLEL-nBG-QCSC) of the composite bioglass.
In the embodiment of the invention, referring to fig. 3, nuclear magnetic characterization is performed on chitosan, quaternized chitosan, and dopamine-modified quaternized chitosan respectively, wherein a) is chitosan, b) is quaternized chitosan, and c) is dopamine-modified quaternized chitosan, wherein in the dopamine-modified quaternized chitosan, catechol groups are successfully grafted on the quaternized chitosan, and the grafting ratio is 6.5%.
The adhesive temperature-sensitive hydrogel of the composite bioglass prepared in this embodiment is detected, as shown in a temperature-sensitive transformation diagram of the adhesive temperature-sensitive hydrogel of the composite bioglass shown in fig. 4, it can be seen that the change curves of the storage modulus (G ') and the dissipation modulus (G ") of the adhesive temperature-sensitive hydrogel of the composite bioglass from 15 ℃ to 55 ℃, and after 35 ℃, the change of the storage modulus (G') and the dissipation modulus (G") of the adhesive temperature-sensitive hydrogel of the composite bioglass tends to be stable; the adhesive temperature-sensitive hydrogel of the composite bioglass is in a gel state after 35 ℃.
Example 3
A preparation method of an adhesive temperature-sensitive hydrogel of composite bioglass comprises the following steps:
at normal temperature, chitosan is dissolved in 87.5mmol/L acetic acid solution, CS solution with the mass concentration of about 1.5% is obtained after magnetic stirring for 12h at room temperature, and then 1.16mL of 2, 3-epoxypropyltrimethylammonium chloride (GMTAC) (9.25-9.30 mmol/L) aqueous solution is slowly added, wherein the molar weight of GMTAC is 1.5-1.6 times of that of amino on chitosan. Stirring and reacting for 20h at 60 ℃, dialyzing and freeze-drying after the reaction is finished to obtain the Quaternized Chitosan (QCS). The QCS yield was determined to be greater than 80%.
Stirring and dissolving the prepared QCS in an aqueous solution at normal temperature to obtain a 0.08g/mL QCS aqueous solution, adjusting the pH value to 4.5 by using a 2M HCl solution, adding dopamine hydrochloride, and fully stirring and dissolving, wherein the molar ratio of the dopamine hydrochloride to the quaternized chitosan is 1.8: 1; coupling reaction at 0-4 deg.c for 16 hr while maintaining pH 4.0; after the reaction is finished, putting the mixture into HCl solution with the pH value of 4.0 and deionized water for dialysis in sequence, and then freeze-drying the mixture to obtain the dopamine modified quaternized chitosan (QCS-C); wherein the yield of QCS-C is more than 80 percent, and the grafting rate of dopamine is about 6 to 7 percent.
Preparing 40 wt% of PDLLA-PEG-PDLLA triblock polymer water solution, and sequentially adding 1.25 wt% of QCS-C and 5 wt% of bioglass; and (3) fully and uniformly stirring to obtain the adhesive temperature-sensitive hydrogel (PLEL-nBG-QCSC) of the composite bioglass.
Example 4
A preparation method of an adhesive temperature-sensitive hydrogel of composite bioglass comprises the following steps:
at normal temperature, chitosan is dissolved in 82mmol/L acetic acid solution, CS solution with the mass concentration of about 1.2% is obtained after magnetic stirring for 8 hours at room temperature, and then 1.16mL of GMTAC (9.25-9.30 mmol/L) aqueous solution is slowly added, wherein the molar weight of GMTAC is 1.5-1.6 times of that of amino on chitosan. Stirring and reacting for 15h at 58 ℃, dialyzing and freeze-drying after the reaction is finished to obtain QCS. The QCS yield was determined to be greater than 80%.
Stirring and dissolving the prepared QCS in an aqueous solution at normal temperature to obtain a 0.1g/mL QCS aqueous solution, adjusting the pH value to 4.5 by using a 2M HCl solution, adding dopamine hydrochloride, and fully stirring and dissolving, wherein the molar ratio of the dopamine hydrochloride to the quaternized chitosan is 1.2: 1; coupling reaction at 0-4 deg.c for 20 hr while maintaining pH 4.5; after the reaction is finished, putting the mixture into HCl solution with pH of 4.5 and deionized water in sequence for dialysis, and then freezing and drying the mixture to obtain the dopamine modified quaternized chitosan; wherein the yield of the dopamine modified quaternized chitosan is more than 80 percent, and the grafting rate of the dopamine is about 6 to 7 percent.
Preparing 35 wt% of PDLLA-PEG-PDLLA triblock polymer water solution, and sequentially adding 1.25 wt% of QCS-C and 4 wt% of bioglass; and (3) fully and uniformly stirring to obtain the adhesive temperature-sensitive hydrogel of the composite bioglass.
Effects of the embodiment
Cell compatibility of adhesive temperature-sensitive hydrogel of composite bioglass
The prepared adhesive temperature-sensitive hydrogel of the composite bioglass is used for detecting the cytotoxicity of the hydrogel through CCK-8. The mouse fibroblast (L929) suspension (inoculation concentration 3X 10) was inoculated in 96-well plates, respectively4One/hole). Firstly, soaking the temperature-sensitive adhesive hydrogel of the composite bioglass into a serum-free culture medium at 37 ℃ at the soaking concentration of 0.1g/mL so as toPreparing a leaching liquor of the temperature-sensitive hydrogel material adhered to the composite bioglass; soaking for 24 hr, filtering with 0.22 μm filter membrane to collect supernatant, diluting with serum-free culture medium to 12.5%, 25%, 50% and 100%, and using the culture medium without leaching solution as blank control at 37 deg.C and 5% CO2After the pre-culture in the incubator for 24h, the culture medium containing leaching liquor gradients with different concentrations is replaced, the culture is continued for 24h, after 48h, 10 muL of CCK-8 is added into each hole, and the growth condition of the cells is represented by a colorimetric method, which is shown in figure 5. From the results in fig. 5, it is shown that L929 cells have no significant cytotoxicity in the culture media with different concentrations of leaching solution, indicating that the biocompatibility of the composite gel is better.
It should be noted that, according to the disclosure and the explanation of the above description, the person skilled in the art to which the present invention pertains may make variations and modifications to the above embodiments. Therefore, the present invention is not limited to the specific embodiments disclosed and described above, and some equivalent modifications and variations of the present invention should be covered by the protection scope of the claims of the present invention. Furthermore, although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

Claims (10)

1. The adhesive temperature-sensitive hydrogel for the composite bioglass is characterized by comprising the following components in percentage by weight: 25-40% of PDLLA-PEG-PDLLA triblock polymer, 1-1.25% of dopamine-modified quaternized chitosan, 1-5% of bioglass and the balance of deionized water; the particle size of the bioglass is 600-800 nm.
2. The adhesive temperature-sensitive hydrogel according to claim 1, wherein the bioglass comprises silica, calcium oxide and phosphorus pentoxide.
3. The adhesive temperature-sensitive hydrogel according to claim 1, wherein the grafting ratio of dopamine in the dopamine-modified quaternized chitosan is 6 to 7%.
4. The adhesive temperature-sensitive hydrogel of claim 1, wherein the bioglass is spherical or spheroidal in shape.
5. The adhesive temperature-sensitive hydrogel according to claim 1, wherein the adhesive temperature-sensitive hydrogel of the composite bioglass is gelatinous at a temperature ranging from 35 ℃ to 70 ℃.
6. The adhesive temperature-sensitive hydrogel of claim 1, wherein the molecular weight of the PDLLA-PEG-PDLLA triblock polymer is 4500-.
7. A preparation method of an adhesive temperature-sensitive hydrogel of composite bioglass is characterized by comprising the following steps:
adding 2, 3-epoxypropyl trimethyl ammonium chloride into an acidic solution of chitosan to realize quaternization of the chitosan, and then collecting to obtain quaternized chitosan; preparing an aqueous solution of the quaternized chitosan, adjusting the pH value to 4.5-5.5, adding dopamine hydrochloride to perform a coupling reaction, and after the reaction is finished, purifying and drying the product to obtain dopamine modified quaternized chitosan;
adding the dopamine modified quaternized chitosan and bioglass into an aqueous solution of a PDLLA-PEG-PDLLA triblock polymer, and uniformly stirring to obtain the adhesive temperature-sensitive hydrogel of the composite bioglass, wherein the mass fraction of the PDLLA-PEG-PDLLA triblock polymer is 25-40%, the mass fraction of the dopamine modified quaternized chitosan is 1-1.25%, the mass fraction of the bioglass is 1-5%, and the particle size of the bioglass is 600-800 nm.
8. The method of claim 7, wherein the quaternized chitosan is prepared by a process comprising: adding aqueous solution of 2, 3-epoxypropyltrimethylammonium chloride into acidic solution of chitosan with the mass fraction of 1-1.5%, stirring and reacting for 15-20h at 50-60 ℃, and after the reaction is finished, dialyzing, freezing and drying to obtain the quaternized chitosan.
9. The method of claim 7, wherein the bioglass is produced by a process comprising: adding ethyl orthosilicate, triethyl phosphate and calcium nitrate tetrahydrate into an ethanol solution in which lauryl amine is dissolved, and stirring for 2-4 hours at the temperature of 30-40 ℃ to obtain a sol solution; then collecting the white precipitate in the sol solution, washing, drying in vacuum, transferring to a high-temperature calcining device, heating to 600-; the composition of the bioglass comprises silicon dioxide, calcium oxide and phosphorus pentoxide.
10. Use of the adhesive temperature-sensitive hydrogel of composite bioglass as defined in any one of claims 1 to 6 or the adhesive temperature-sensitive hydrogel of composite bioglass prepared by the preparation method as defined in any one of claims 7 to 9 in the preparation of a medicament for healing skin wounds.
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CN111110853B (en) * 2019-12-16 2023-05-05 温州医科大学 Bioadhesive temperature-sensitive material, preparation method thereof and application of drug carrier
CN112156222B (en) * 2020-09-22 2021-10-26 华南理工大学 Preparation method of hemostatic, antibacterial and healing-promoting frozen gel sponge
CN113842493B (en) * 2021-09-13 2022-12-02 深圳先进技术研究院 Preparation method of temperature-sensitive hydrogel and temperature-sensitive hydrogel
CN115814146B (en) * 2022-11-01 2023-12-22 山东大学 Preparation method of hemostatic powder with bionic coagulation mechanism

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004072100A2 (en) * 2003-02-07 2004-08-26 The Regents Of The University Of California Nell peptide expression systems and bone formation activity of nell peptide
WO2013077476A1 (en) * 2011-11-21 2013-05-30 한국과학기술원 Hydrogel comprising catechol group-coupled chitosan or polyamine and poloxamer comprising thiol group coupled to end thereof, preparation method thereof, and hemostat using same
CN103251986A (en) * 2013-05-17 2013-08-21 四川大学 Use of PDLLLA (Poly Dl Lactic Acid)-PEG (Polyethylene Glycol)-PDLLA triblock copolymer in preparing medical anti-adhesion material
CN103705968A (en) * 2013-12-30 2014-04-09 深圳先进技术研究院 Medical chitosan compound moisturizing dressing and preparation method thereof
CN104096262A (en) * 2013-04-09 2014-10-15 上海交通大学医学院附属第九人民医院 Collagen/chitosan/mesoporous bioactive glass composite nanofiber membrane material and preparation method thereof
EP2813213A1 (en) * 2013-06-12 2014-12-17 Nederlandse Organisatie voor toegepast -natuurwetenschappelijk onderzoek TNO Injectable hydrogel composition, method for the preparation and uses thereof
CN107185049A (en) * 2017-05-31 2017-09-22 合肥创沃科技有限公司 A kind of preparation method of chitosan compound biological activity glass tissue renovation material
CN108434091A (en) * 2018-06-13 2018-08-24 西安交通大学 A kind of self-healing hydrogel and preparation method thereof of wound healing and oncotherapy
CN108912352A (en) * 2018-07-09 2018-11-30 西安交通大学 A kind of antibacterial adherency injection aquagel dressing and its preparation method and application
CN109663146A (en) * 2019-02-01 2019-04-23 浙江大学 A kind of antibacterial, the temperature sensitive chitosan gel rubber dressing of injection type and preparation method thereof

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004072100A2 (en) * 2003-02-07 2004-08-26 The Regents Of The University Of California Nell peptide expression systems and bone formation activity of nell peptide
WO2013077476A1 (en) * 2011-11-21 2013-05-30 한국과학기술원 Hydrogel comprising catechol group-coupled chitosan or polyamine and poloxamer comprising thiol group coupled to end thereof, preparation method thereof, and hemostat using same
CN104096262A (en) * 2013-04-09 2014-10-15 上海交通大学医学院附属第九人民医院 Collagen/chitosan/mesoporous bioactive glass composite nanofiber membrane material and preparation method thereof
CN103251986A (en) * 2013-05-17 2013-08-21 四川大学 Use of PDLLLA (Poly Dl Lactic Acid)-PEG (Polyethylene Glycol)-PDLLA triblock copolymer in preparing medical anti-adhesion material
EP2813213A1 (en) * 2013-06-12 2014-12-17 Nederlandse Organisatie voor toegepast -natuurwetenschappelijk onderzoek TNO Injectable hydrogel composition, method for the preparation and uses thereof
CN103705968A (en) * 2013-12-30 2014-04-09 深圳先进技术研究院 Medical chitosan compound moisturizing dressing and preparation method thereof
CN107185049A (en) * 2017-05-31 2017-09-22 合肥创沃科技有限公司 A kind of preparation method of chitosan compound biological activity glass tissue renovation material
CN108434091A (en) * 2018-06-13 2018-08-24 西安交通大学 A kind of self-healing hydrogel and preparation method thereof of wound healing and oncotherapy
CN108912352A (en) * 2018-07-09 2018-11-30 西安交通大学 A kind of antibacterial adherency injection aquagel dressing and its preparation method and application
CN109663146A (en) * 2019-02-01 2019-04-23 浙江大学 A kind of antibacterial, the temperature sensitive chitosan gel rubber dressing of injection type and preparation method thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Catechol modified quaternized chitosan enhanced wet adhesive and antibacterial properties of injectable thermo-sensitive hydrogel for wound healing;Zhiqiang Zheng等;《Carbohydrate Polymers》;20200803;第249卷;第1-12页 *
Platelet-Rich Plasma-Loaded Poly(D,L-lactide)- Poly(ethylene glycol)-Poly(D,L-lactide) Hydrogel Dressing Promotes Full-Thickness Skin Wound Healing in a Rodent Model;Manle Qiu等;《Int. J. Mol. Sci.》;20160624;第17卷;第1-16页 *
Thermogelling chitosan–collagen–bioactive glass nanoparticle hybrids as potential injectable systems for tissue engineering;Cheisy D.F. Moreira等;《Materials Science and Engineering C》;20150925;第58卷;第1207-1216页 *
温敏型凝胶用聚合物及在药剂学中的应用;冉勇等;《中国新药杂志》;20090228(第04期);第318-322、339页 *

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