Thermo-sensitive hydrogel stent and preparation method thereof

Abstract

The invention discloses a temperature-sensitive hydrogel stent and a preparation method thereof, and belongs to the technical field of biomedicine. The temperature-sensitive hydrogel scaffold is prepared from the following raw materials in parts by mass: 1 to 10 parts of a temperature-sensitive agent, 20 to 50 parts of starch, 5 to 30 parts of carrageenan, 5 to 20 parts of a water locking agent, 1 to 20 parts of edible salt and 0.1 to 1 part of an antibacterial agent, the temperature-sensitive agent comprises gelatin, glucose and mannitol. The novel temperature-sensitive hydrogel stent with high strength, good moisture management capability and antibacterial property is provided by accurately regulating and controlling the raw material composition and optimizing the preparation process, so that the requirement of the biomedicine field on a high-performance stent material is met. The hydrogel scaffold has certain water absorbability and water-retaining property, and functions of water management, drug or cell delivery and the like of the hydrogel scaffold in biomedical application are facilitated.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to a temperature-sensitive hydrogel scaffold and a preparation method thereof. Background Art

[0002] At present, in the field of biomedical engineering, hydrogel scaffolds have been widely used due to their unique properties such as good biocompatibility, adjustable degradation performance and unique three-dimensional structure. An ideal hydrogel scaffold has certain mechanical strength, biodegradability, good biocompatibility, appropriate pore diameter and porosity, which can provide an ideal microenvironment for cell interaction, cell migration, proliferation and differentiation. Thermosensitive hydrogel scaffolds are synthesized from materials with good biocompatibility, which is conducive to cell adhesion and proliferation. Thermosensitive hydrogel scaffolds have the properties of fluids before gelation, and can eventually form hydrogels with adaptive shapes according to the injection position, which has great advantages in irregular cartilage repair, and this injectability also avoids surgical trauma, making treatment more convenient. In addition, while serving as a cell scaffold, hydrogels can also carry various active substances, such as peptides, genes, proteins, cells and small molecule drugs, to achieve the role of promoting the proliferation and directional differentiation of chondrocytes or stem cells.

[0003] Among them, thermosensitive hydrogel scaffolds are widely used in the biomedical field due to their unique temperature responsiveness; this material can change its physical properties, such as swelling and stiffness, according to changes in ambient temperature, so as to adapt to different physiological environments or treatment needs. Therefore, it can adjust its physical state according to changes in ambient temperature, thereby achieving controlled release of drugs or directed differentiation of cells under specific physiological conditions, providing a more sophisticated means of regulation for tissue repair and regeneration.

[0004] However, traditional thermosensitive hydrogel scaffold materials often have problems such as difficult water retention / water separation, insufficient mechanical properties, poor product stability, and lack of effective antibacterial properties, which limit their application in complex biological environments. In order to improve the comprehensive performance of hydrogel scaffolds, relevant scientific researchers still need to make further improvements. For example, the mechanical properties of traditional thermosensitive hydrogel scaffold materials will deteriorate after water loss. How to ensure that the water content of hydrogel scaffold materials changes due to temperature changes without affecting the mechanical strength is a problem that relevant researchers still need to solve. Therefore, reasonable regulation of the types and proportions of functional components has become the key to improving the performance of hydrogel scaffolds. In addition, the preparation process of existing thermosensitive hydrogel scaffold materials is often cumbersome, the gelation conditions are harsh, and the resulting scaffolds still need to be optimized in terms of mechanical strength and water release characteristics. Therefore, it is particularly important to develop a thermosensitive hydrogel scaffold with a reasonable raw material ratio, a simple preparation process, and excellent performance. Summary of the invention

[0005] The object of the present invention is to provide a thermosensitive hydrogel scaffold and a preparation method thereof to solve the above-mentioned problems in the background technology. The present invention provides a novel thermosensitive hydrogel scaffold with high strength, good moisture management ability and antibacterial properties by precisely controlling the raw material composition and optimizing the preparation process to meet the demand for high-performance scaffold materials in the biomedical field. The hydrogel scaffold has certain water absorption and water retention, which contributes to its functions such as moisture management, drug or cell delivery in biomedical applications.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] One of the technical solutions of the present invention is to provide a thermosensitive hydrogel scaffold, wherein the raw materials, calculated by weight, include:

[0008] 1-10 parts of thermosensitive agent, 20-50 parts of starch, 5-30 parts of carrageenan, 5-20 parts of water-locking agent, 1-20 parts of edible salt and 0.1-1 part of antibacterial agent;

[0009] The thermosensitive agent comprises gelatin, glucose and mannitol.

[0010] Preferably, the mass ratio of the gelatin, glucose and mannitol is 10-50:1-30:5-30.

[0011] Preferably, the water-locking agent is glucomannan and / or sodium hyaluronate.

[0012] Preferably, the edible salt is one or more of sodium chloride, potassium chloride, sodium nitrate and potassium nitrate.

[0013] Preferably, the antibacterial agent is nano titanium dioxide or nano zinc oxide.

[0014] Preferably, the thermosensitive hydrogel scaffold is composed of the following raw materials in parts by weight: 10 parts of thermosensitive agent, 20 parts of starch, 20 parts of carrageenan, 10 parts of edible salt and 1 part of antibacterial agent.

[0015] The second technical solution of the present invention is to provide a method for preparing the above-mentioned thermosensitive hydrogel scaffold, comprising the following steps:

[0016] The starch, carrageenan, edible salt and antimicrobial agent are stirred and mixed in water, and then a thermosensitive agent and ethanol are added to obtain a gel solution;

[0017] The liquid to be gelled is subjected to gelling treatment to obtain a hydrogel; and the hydrogel is immersed in water to obtain a temperature-sensitive hydrogel scaffold.

[0018] Preferably, the temperature of the gel treatment is 100°C.

[0019] Preferably, the immersion time in water is 24-48 hours.

[0020] The third technical solution of the present invention is to provide an application of the above-mentioned thermosensitive hydrogel scaffold in the biomedical field.

[0021] The beneficial technical effects of the present invention are as follows:

[0022] The present invention provides a new type of thermosensitive hydrogel scaffold with high strength, good moisture management ability and antibacterial properties by precisely controlling the raw material composition and optimizing the preparation process, so as to meet the demand for high-performance scaffold materials in the biomedical field, and is suitable for use in the fields of tissue repair and regeneration, drug delivery systems, wound care, etc. The hydrogel scaffold has certain water absorption and water retention, and the active ingredients are dissolved by water molecules to achieve the effect of wrapping, and then the release effect is achieved by the release of water molecules; and the adsorption and release of water molecules in the hydrogel are regulated by temperature. Therefore, this new type of thermosensitive hydrogel scaffold contributes to its functions such as moisture management, drug or cell delivery in biomedical applications. However, this concept of active ingredient wrapping and release has not been reported so far.

[0023] Among the raw material components of the present invention, starch and carrageenan are the main components of the hydrogel, which provide the basic structure and shape of the scaffold. At the same time, the two also have certain water absorption and water retention, which is helpful for the moisture management of the hydrogel scaffold in biomedical applications. The water-locking agent is an important reason for water retention and water separation. Through a large number of hydrogen bonds in the water-locking agent, its interaction with water molecules is realized, and the strength of the hydrogen bond effect is regulated by temperature regulation, thereby realizing the absorption and release of water molecules. The addition of edible salt will have a positive effect on the physical properties and stability of the thermosensitive hydrogel scaffold of the present invention, and help to form a porous scaffold morphology. The added antibacterial agent gives the hydrogel scaffold good antibacterial properties, which can effectively prevent microbial contamination of the scaffold during use and ensure biosafety. Ethanol is used as a solvent and coagulant in the preparation process, which helps to form a stable hydrogel structure. The thermosensitive agent in the raw materials gives the hydrogel scaffold a temperature-sensitive property, allowing it to change its physical properties according to changes in ambient temperature; gelatin gives the product good biocompatibility and temperature sensitivity, and combined with glucose and mannitol, it can not only adjust the osmotic pressure of the gel, but also further enhance the temperature-sensitive performance by affecting the intermolecular interaction. These raw materials together give the hydrogel scaffold unique temperature sensitivity and structural characteristics, giving it a wide range of application prospects in biomedicine and other fields. DETAILED DESCRIPTION

[0024] Now, various exemplary embodiments of the present invention are described in detail, and this detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention. It should be understood that the terms described in the present invention are only for describing specific embodiments and are not used to limit the present invention.

[0025] In addition, for the numerical range in the present invention, it is understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. The intermediate value in any stated value or stated range, and each smaller range between any other stated value or intermediate value in the range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0026] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the invention pertains. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention.

[0027] The words “include,” “including,” “have,” “contain,” etc. used in the present invention are open-ended terms, meaning including but not limited to.

[0028] The "room temperature" in the present invention is 10-30°C unless otherwise specified.

[0029] All raw materials used in the following examples and comparative examples of the present invention are commercially available products.

[0030] Example 1

[0031] A thermosensitive hydrogel scaffold is composed of the following raw materials in percentage by mass:

[0032] Thermosensitive agent 10wt%, soluble starch 35wt%, carrageenan 30wt%, water lock agent (glucomannan) 15%, edible salt (sodium chloride) 9wt%, antibacterial agent (nano titanium dioxide) 1wt%;

[0033] The thermosensitive agent is composed of gelatin, glucose and mannitol in a mass ratio of 4:2:1.

[0034] The specific preparation process is as follows:

[0035] Soluble starch, carrageenan, edible salt and antibacterial agent were placed in 100 mL of water at room temperature and stirred for 5 minutes, then heated to 70°C, and then a thermosensitive agent and 20 mL of anhydrous ethanol were added and stirred for 5 minutes to obtain a gel solution;

[0036] The gel solution is heated to 100°C and stirred to evaporate all the ethanol therein. When the solution is in a gel state, it is molded and cooled to prepare a hydrogel. The hydrogel is immersed in water for 24-48 hours and then taken out to obtain a thermosensitive hydrogel scaffold.

[0037] It was measured that the mechanical strength of the thermosensitive hydrogel scaffold prepared in this embodiment was: tensile strength 0.018 MPa, elongation at break 36.08%.

[0038] The water dripping amount was measured by the suspension method. The test results showed that the amount of water molecules released by the product was: 3.1g in 10min, 7g in 20min, and 10.3g in 30min.

[0039] In the field of wound care, the appropriate hygroscopicity and water retention of hydrogels help maintain a moist environment for wounds and promote wound healing; in the field of tissue engineering, good water management capabilities help cell adhesion and proliferation. The amount of water molecules released by the product of the present invention increases slowly over time, indicating that the material has good water retention and can maintain a moist environment for a long time.

[0040] Example 2

[0041] A thermosensitive hydrogel scaffold is composed of the following raw materials in percentage by mass:

[0042] Thermosensitive agent 10wt%, soluble starch 40wt%, carrageenan 20wt%, water lock agent (glucomannan) 20%, edible salt (potassium chloride) 9wt%, antibacterial agent (nano zinc oxide) 1wt%;

[0043] The thermosensitive agent is composed of gelatin, glucose and mannitol in a mass ratio of 3:1:1.

[0044] The specific preparation process is as follows:

[0045] Soluble starch, carrageenan, edible salt and antibacterial agent were placed in 100 mL of water at room temperature and stirred for 5 minutes, then heated to 70°C, and then a thermosensitive agent and 20 mL of anhydrous ethanol were added and stirred for 5 minutes to obtain a gel solution;

[0046] The gel solution is heated to 100°C and stirred to evaporate all the ethanol therein. When the solution is in a gel state, it is molded and cooled to prepare a hydrogel. The hydrogel is immersed in water for 24-48 hours and then taken out to obtain a thermosensitive hydrogel scaffold.

[0047] It was measured that the mechanical strength of the thermosensitive hydrogel scaffold prepared in this embodiment was: tensile strength 0.026 MPa, elongation at break 46.63%.

[0048] The amount of water dripping was measured by the suspension method. The test results showed that the amount of water molecules released by the product was: 1.7g in 10min, 3.9g in 20min, and 5.3g in 30min.

[0049] Example 3

[0050] A thermosensitive hydrogel scaffold is composed of the following raw materials in percentage by mass:

[0051] Thermosensitive agent 5wt%, soluble starch 30wt%, carrageenan 30wt%, water lock agent (sodium hyaluronate) 15%, edible salt (potassium chloride) 19wt%, antibacterial agent (nano zinc oxide) 1wt%;

[0052] The thermosensitive agent is composed of gelatin, glucose and mannitol in a mass ratio of 2:1:1.

[0053] The specific preparation process is as follows:

[0054] Soluble starch, carrageenan, edible salt and antibacterial agent were placed in 100 mL of water at room temperature and stirred for 5 minutes, then heated to 70°C, and then a thermosensitive agent and 20 mL of anhydrous ethanol were added and stirred for 5 minutes to obtain a gel solution;

[0055] The gel solution is heated to 100°C and stirred to evaporate all the ethanol therein. When the solution is in a gel state, it is molded and cooled to prepare a hydrogel. The hydrogel is immersed in water for 24-48 hours and then taken out to obtain a thermosensitive hydrogel scaffold.

[0056] It was measured that the mechanical strength of the thermosensitive hydrogel scaffold prepared in this embodiment was: tensile strength 0.013 MPa, elongation at break 38.50%.

[0057] The water dripping amount was measured by the suspension method. The test results showed that the water molecule release amount of the product was: 1.9g in 10min, 4.0g in 20min, and 5.1g in 30min.

[0058] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A thermosensitive hydrogel scaffold, characterized in that: Raw materials, calculated by mass, include: 1-10 parts of thermosensitive agent, 20-50 parts of starch, 5-30 parts of carrageenan, 5-20 parts of water-locking agent, 1-20 parts of edible salt and 0.1-1 part of antibacterial agent; The thermosensitive agent comprises gelatin, glucose and mannitol.

2. The thermosensitive hydrogel scaffold according to claim 1, characterized in that: The mass ratio of the gelatin, glucose and mannitol is 10-50:1-30:5-30.

3. The thermosensitive hydrogel scaffold according to claim 1, characterized in that: The water-locking agent is glucomannan and / or sodium hyaluronate.

4. The thermosensitive hydrogel scaffold according to claim 1, characterized in that: The edible salt is one or more of sodium chloride, potassium chloride, sodium nitrate and potassium nitrate.

5. The thermosensitive hydrogel scaffold according to claim 1, characterized in that: The antibacterial agent is nano titanium dioxide or nano zinc oxide.

6. A method for preparing a thermosensitive hydrogel scaffold according to any one of claims 1 to 5, characterized in that: The following steps are involved: The starch, carrageenan, edible salt and antimicrobial agent are stirred and mixed in water, and then a thermosensitive agent and ethanol are added to obtain a gel solution; The liquid to be gelled is subjected to gelling treatment to obtain a hydrogel; and the hydrogel is immersed in water to obtain a temperature-sensitive hydrogel scaffold.

7. The preparation method according to claim 6, characterized in that: The temperature of the gel treatment is 100°C.

8. The preparation method according to claim 6, characterized in that: The immersion time in water is 24-48h.

9. Use of the thermosensitive hydrogel scaffold according to any one of claims 1 to 5 in the biomedical field.