Adaptive hypercontracted muscle tendon adhesives of janus structure and methods of making the same

Abstract

The application discloses a janus structure adaptive super-shrinking tendon adhesive and a preparation method thereof, and belongs to the technical field of biological medical material preparation methods. The stable adhesive pre-solution is coated on a crystalline hydrophilic polymer shrinkage film to obtain the janus structure adaptive super-shrinking tendon adhesive. The janus structure adaptive super-shrinking tendon adhesive exhibits an innovative janus structure design, so that better biocompatibility and function regulation can be realized. The outer layer has excellent anti-tissue adhesion and self-cleaning functions, and the inner layer is a high-strength and excellent-toughness adhesive layer. Under humid conditions, the adhesive can rapidly shrink, and can perfectly fit and wrap the complex and irregular tissue surfaces of tendons, muscles and hearts. Moreover, by changing the molecular structure and micro-morphology of the adhesive, the thermal performance, degradability, swelling rate and adhesion of the adhesive can be optimized, which is crucial for improving the clinical application effect of the adhesive.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medical material preparation methods, in particular to a Janus structure self-adaptive super-shrinkage tendon adhesive and a preparation method thereof. BACKGROUND

[0002] Tendon is a complex connective tissue that can effectively transmit muscle force to the skeleton. Its structure, function and physiological characteristics determine that tendon tissue needs to bear extreme and repeated mechanical stress. These mechanical requirements also pose a huge hidden danger to tendon injury. Moreover, due to the low cellularity, low vascularity and low metabolic activity of tendon tissue, the recovery of injured tendon is extremely poor. Such injuries mainly affect active workers, the elderly and athletes all over the world. At present, tendon injury affects nearly 30 million people, and as the life expectancy continues to increase and the number of people engaged in sports continues to increase, it is expected that the number of people suffering from such injuries will increase. Every year, a large amount of productivity and huge medical burden are caused by these injuries all over the world. Therefore, seeking safe and efficient, simple and easy tendon repair technology has always been the focus of attention of researchers and clinicians at home and abroad.

[0003] In recent years, many studies have focused on developing tendon adhesives with excellent biocompatibility and mechanical properties, and exploring their specific applications. Among them, polymer-based tendon adhesives have attracted widespread attention. These materials not only can achieve controlled degradation in vivo, but also have the potential to regulate biological signals. The research scope of such tendon adhesives ranges from natural materials (such as proteins and polysaccharides) to synthetic polymers (such as polyvinyl alcohol and polylactic acid), showing their diversity and applicability. Tendon adhesives are easy and fast to operate, and can be combined with tendon transplantation and catheter technology, so they have become a hot spot in tendon surgery research and have the potential to replace traditional suturing. However, these adhesives still have deficiencies in comprehensive performance such as mechanical strength and adhesion strength, and their mechanism of action is not clear, which leads to relatively few clinical application studies. Therefore, further research and development are crucial for improving the performance and clinical application of tendon adhesives.

[0004] Although there have been many research results on tendon adhesives, the products on the market still have certain limitations, such as difficult operation, insufficient long-term biological tolerance or unsatisfactory regeneration effect. Therefore, in-depth research and development of new tendon adhesives, especially emphasizing their biological adaptability, mechanical stability, degradability and functionality, are the key to achieving more effective tendon repair.

[0005] In combination with the above background, the present application aims to provide a new type of tendon adhesive with excellent performance and wide application prospects to achieve more effective tendon injury repair and promote the development of tendon regeneration research. SUMMARY

[0006] The application aims to provide a janus structure adaptive super-shrinking muscle tendon adhesive and a preparation method thereof, and solve the problems of poor mechanical strength, weak adhesion strength and surrounding tissue adhesion caused by the current commercial adhesive.

[0007] To achieve the above-mentioned purpose, the application discloses a preparation method of a janus structure adaptive super-shrinking muscle tendon adhesive, which comprises the following steps:

[0008] S1, using polyethylene glycol (PEG) as a raw material, a crystalline hydrophilic polymer shrinking film is prepared;

[0009] S2, a stable lipoic acid adhesive pre-solution is prepared by mixing a lipoic acid compound and lipoic acid to which an electrophilic reagent is added;

[0010] S3, the lipoic acid adhesive pre-solution is uniformly coated on the crystalline hydrophilic polymer shrinking film to obtain a janus structure adaptive super-shrinking muscle tendon adhesive.

[0011] Preferably, the specific preparation method of the crystalline hydrophilic polymer shrinking film in step S1 is as follows:

[0012] S1-2, polyethylene glycol is dissolved in water to obtain a polyethylene glycol aqueous solution;

[0013] S1-3, the polyethylene glycol aqueous solution is poured on a culture dish and dried at 30-80 DEG C for 4-12 hours to evaporate water, so as to obtain the crystalline hydrophilic polymer shrinking film.

[0014] Preferably, in step S1-1, the molecular weight of the polyethylene glycol is 1000-10000, and the mass percentage concentration of the polyethylene glycol in the mixed solution is 1%-10%.

[0015] Preferably, the preparation method of the lipoic acid adhesive pre-solution in step S2 specifically comprises the following steps:

[0016] S2-1, a lipoic acid compound is dissolved in anhydrous ethanol to obtain a lipoic acid compound solution;

[0017] S2-2, lipoic acid to which an electrophilic reagent is added (lipoic acid-NHS) is dissolved in an organic reagent to obtain an electrophile solution;

[0018] S2-3, the lipoic acid compound solution and the electrophile solution are mixed and then placed for 0.5-3 hours to obtain a lipoic acid adhesive pre-solution.

[0019] Preferably, in step S2-1, the mass percentage concentration of the lipoic acid compound in the lipoic acid compound solution is 4%-10%; in step S2-2, the mass percentage concentration of the lipoic acid with added electrophilic reagent in the electrophilic solution is 20%-30%; the electrophile is any one of N-hydroxysuccinimide, N-hydroxyphthalimide ester, and tetrafluorophenol ester; the organic solvent is any one of anhydrous ethanol, methanol, and dimethyl sulfoxide.

[0020] Preferably, in step S2-2, the mass concentration of the electrophilic stabilizer is 2% to 6%.

[0021] Preferably, in steps S2-3, the volume ratio of anhydrous ethanol in the lipoic acid compound solution to the organic solvent in the electrophilic solution is 10:1.

[0022] Preferably, in step S3, the crystalline hydrophilic polymer shrink film, after drying, becomes an antifouling layer, and the thioctic acid adhesive pre-solution, after drying, becomes an adhesive layer. The bonding method between the antifouling layer and the adhesive layer is at least one of impregnation, in-situ polymerization, layer-by-layer self-assembly, and physical cross-linking.

[0023] The present invention also provides an adaptive supercontractile tendon adhesive with a Janus structure, which is prepared by the above-described preparation method. The adaptive supercontractile tendon adhesive includes an outer layer and an inner layer. The outer layer is an antifouling layer with anti-tissue adhesion and self-cleaning functions, and the inner layer is an adhesive layer with high strength and excellent toughness.

[0024] Therefore, the present invention has the following beneficial effects:

[0025] This invention employs a Janus structure to achieve better biocompatibility and functional regulation. Its outer layer possesses excellent anti-tissue adhesion and self-cleaning properties, while the inner layer is a high-strength and highly resilient adhesive layer. Under humid conditions, this adhesive can rapidly shrink, perfectly adhering to and encapsulating complex and irregular tissue surfaces such as tendons, muscles, and the heart. The preparation method is simple, controllable, safe, environmentally friendly, and easily scalable. This adhesive effectively resists adhesion to surrounding tissues and maintains stable tissue adhesion in humid environments.

[0026] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0027] Figure 1 This demonstrates the conformability of the adaptive supercontractile tendon adhesive with a janus structure prepared in Example 1.

[0028] Figure 2 The interfacial adhesion of the adaptive supercontractile tendon adhesive with a janus structure prepared in Example 1 is demonstrated.

[0029] Figure 3 Contractility test of the adaptive supercontractile tendon adhesive with janus structure prepared in Example 1;

[0030] Figure 4 Adhesion test of the adaptive supercontractile tendon adhesive with janus structure prepared in Example 1;

[0031] Figure 5 An in vivo rat illustration of the ischial tendon bonded with the adaptive supercontractile tendon adhesive with a janus structure prepared in Example 1. Detailed Implementation

[0032] The technical solution of the present invention will be further described below through examples and embodiments.

[0033] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0034] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can be appropriately combined to form other embodiments that can be understood by those skilled in the art. These other embodiments are also covered within the scope of protection of this invention.

[0035] Example 1

[0036] This embodiment provides an adaptive supercontractile tendon adhesive with a Janus structure, the preparation method of which includes the following steps:

[0037] Step 1: Dissolve 1g of polyethylene glycol polymer in 50ml of deionized water to obtain a polyethylene glycol aqueous solution; pour the above aqueous solution onto a flat substrate and dry at 45℃ for 6 hours to obtain a crystalline hydrophilic polymer shrink film. Perform cold stretching (400% strain) on a stretching machine to finally obtain a shrinkable film.

[0038] Step 2: Dissolve 0.1g of lipoic acid compound in 2ml of anhydrous ethanol, add 0.05g of electrophilic lipoic acid dissolved in 0.2ml of dimethyl sulfoxide, mix well and let stand for 1 hour to obtain a stable lipoic acid adhesive pre-solution.

[0039] Step 3: The thioctic acid-based adhesive pre-solution obtained in Step 2 is uniformly coated onto the surface of the crystalline hydrophilic polymer shrinkage film obtained in Step 1 to obtain an adaptive super-contractile tendon adhesive with a Janus structure.

[0040] The conformability of the adaptive supercontractile tendon adhesive with a Janus structure prepared in this embodiment is demonstrated as follows: Figure 1 As shown, by Figure 1 It is known that the adaptive super-contractile tendon adhesive can rapidly contract within 5 seconds and achieve tight wrapping of irregular objects within one minute.

[0041] The interfacial adhesion of the adaptive supercontractile tendon adhesive with a Janus structure prepared in this embodiment is shown as follows: Figure 2 As shown, through Figure 2 It can be clearly seen that the adaptive super-contraction tendon adhesive has a strong interfacial adhesion to the substrate.

[0042] The contractility test of the adaptive supercontractile tendon adhesive with a Janus structure prepared in this embodiment is as follows: Figure 3 As shown; via Figure 3 It is understood that the adaptive super-contraction tendon adhesive has a maximum contraction rate of up to 65%, which can provide good contractile force, thereby making the tissue tightly wrapped.

[0043] The adaptive supercontractile tendon adhesive prepared in this embodiment was subjected to adhesion tests on glass and pigskin, and the results are as follows: Figure 4 As shown, this adaptive supercontractile tendon adhesive exhibits strong adhesion on both glass and wet pigskin, with a maximum adhesion value of up to 230 kPa.

[0044] The rat in vivo bonding of the ischial tendon with the adaptive supercontractile tendon adhesive containing the Janus structure prepared in this embodiment is shown as follows. Figure 5 As shown in the figure, tendon bonding was performed in rats, demonstrating that the adaptive supercontractile tendon adhesive can effectively bond damaged tendons.

[0045] Example 2

[0046] This embodiment provides an adaptive supercontractile tendon adhesive with a Janus structure, the preparation method of which includes the following steps:

[0047] The method is basically the same as in Example 1, except that the mass concentration of the polyethylene glycol polymer aqueous solution in step one is 5% (5 g polyethylene glycol dissolved in 50 mL of water); and the mass concentration of the thioctic acid compound in step two is 8% (0.4 g thioctic acid dissolved in 5 mL of anhydrous ethanol).

[0048] Example 3

[0049] This embodiment provides an adaptive supercontractile tendon adhesive with a Janus structure, the preparation method of which includes the following steps:

[0050] The same as example 1, except that the mass concentration of the polyethylene glycol polymer aqueous solution in step one is 10% (5 g polyethylene glycol is dissolved in 50 mL water); the mass concentration of the lipoic acid compound in step two is 10% (0.80 g lipoic acid is dissolved in 9.20 g anhydrous ethanol).

[0051] The above only describes the preferred embodiments of the present application, and it should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered within the scope of protection of the present application.

Claims

1. Process for the preparation of an adaptive hypercontractile teno-adhesive of the Janus structure, characterized in that, The method comprises the following steps: S1, using polyethylene glycol as raw material, a crystalline hydrophilic polymer shrinkage film is prepared; S2, using lipoic acid compound as monomer, a stable lipoic acid adhesive pre-solution is prepared; S3, the lipoic acid adhesive pre-solution is uniformly coated on the crystalline hydrophilic polymer shrinkage film, and dried at 45 DEG C to obtain a janus structure self-adapting super-shrinkage tendon adhesive; The specific preparation method of the crystalline hydrophilic polymer shrinkage film in step S1 is as follows: S1-1, polyethylene glycol is dissolved in deionized water to obtain a polyethylene glycol aqueous solution; S1-2, the polyethylene glycol solution is cast on a culture dish, dried at 30-80 DEG C for 4-12 hours to evaporate water, a film is obtained, and then the film is cold-drawn on a stretching machine with a strain of 400% to obtain a crystalline hydrophilic polymer shrinkage film.

2. The method of claim 1, wherein the Janus-structured adaptive hypercontractile muscle tendon adhesive is prepared by, In step S1-1, the molecular weight of polyethylene glycol is 1000-10000, and the mass percentage concentration of polyethylene glycol in the mixed solution is 1%-10%.

3. The method of claim 1, wherein the Janus structure adaptive hyper- contractile muscle tendon adhesive is prepared by, The preparation method of the lipoic acid adhesive pre-solution in step S2 specifically comprises the following steps: S2-1, lipoic acid compound is dissolved in anhydrous ethanol to obtain a lipoic acid compound solution; S2-2, the lipoic acid solution added with electrophilic reagent is dissolved in an organic reagent to obtain an electrophile solution; S2-3, the lipoic acid compound solution and the electrophile solution are mixed and then placed for 0.5-3h to obtain a lipoic acid adhesive pre-solution.

4. The method of claim 3, wherein the Janus structure adaptive hyper- contractile muscle tendon adhesive is prepared by, In step S2-1, the mass percentage concentration of lipoic acid compound in the lipoic acid compound solution is 4%-10%; in step S2-2, the mass percentage concentration of lipoic acid added with electrophilic reagent in the electrophile solution is 20%-30%; the electrophile is any one of N-hydroxy succinimide, N-hydroxy phthalimide ester, and tetrafluorophenol ester; and the organic solvent is any one of anhydrous ethanol, methanol, and dimethyl sulfoxide.

5. The method of claim 3, wherein the Janus structure adaptive hyper- contractile muscle tendon adhesive is prepared by, In step S2-3, the volume ratio of anhydrous ethanol in the lipoic acid compound solution to the organic solvent in the electrophile solution is 10:

1.

6. The method of claim 1, wherein the janus structure of the adaptive hyper- contractile tendon adhesive is prepared by, In step S3, the crystalline hydrophilic polymer shrinkage film after drying is a stain-resistant layer, and the lipoic acid adhesive pre-solution after drying is an adhesive layer; the combination method of the stain-resistant layer and the adhesive layer is at least one of immersion method, in-situ polymerization, layer-by-layer self-assembly, and physical crosslinking.

7. An adaptive hypercontracted tendon adhesive of the Janus structure, characterized in that The janus structure self-adapting super-shrinkage tendon adhesive is prepared by the preparation method of any one of claims 1-6, and comprises an outer layer and an inner layer; the outer layer is a stain-resistant layer with anti-tissue adhesion and self-cleaning functions, and the inner layer is an adhesive layer with high strength and excellent toughness.

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