Preparation method of a bionic suction cup

Abstract

The application discloses a preparation method of a bionic suction disc. The bionic suction disc is divided into a suction disc body and a temperature-sensitive expansion layer arranged at the middle part of the suction disc body. The suction disc body is mainly made of PAAc-NHS ester, gelatin methacrylate (GelMA) and gelatin. The combination of the two materials can realize good adsorption effect of the suction disc on a wet surface and a surface with texture gullies, and the suction disc does not produce toxicity and stimulation. The suction disc has a good prospect when applied to adsorption and traction of tissues and organs in surgery.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically a method for preparing a bionic suction cup. Background Technology

[0002] With the maturation and widespread adoption of laparoscopic technology in recent years, an increasing number of abdominal surgeries can be performed laparoscopically. The advantage of laparoscopic surgery over traditional open surgery is that it treats patients with minimal trauma. However, due to the limited space in the abdominal cavity, laparoscopic surgery places high demands on the surgeon, especially in the upper abdomen where the operating space is limited, posing significant challenges. To better expose the surgical area, blunt instruments or sutures are often used to suspend tissue; however, this not only further reduces the operating space but may also cause unnecessary damage to normal tissue. In recent years, polymeric biomaterials have seen rapid development, with many materials available for tissue adhesion, such as fibrin glue, gelatin, collagen, oxidized cellulose, and polymers. However, most of these materials cannot adhere to moist surfaces or have poor mechanical properties, making them difficult to use in the peritoneal cavity containing peritoneal fluid.

[0003] The applicant disclosed a double-sided suction cup for liver retraction in patent number CN 211460332 U, which is used to adsorb and pull organs such as the liver during laparoscopic upper abdominal surgery. However, the negative pressure suction cup requires an additional negative pressure device, which makes the operation more complicated. Furthermore, the negative pressure of the conventional silicone suction cup is not maintained for a long time due to slow air leakage at the texture grooves, and the adsorption effect is not ideal. Summary of the Invention

[0004] The present invention aims to at least partially overcome the above-mentioned technical problems and / or other potential problems existing in the prior art: to provide a method for preparing a biomimetic suction cup that achieves good adsorption effect on wet surfaces and textured surfaces, without producing toxicity or irritation.

[0005] The technical solution of the present invention is as follows: a method for preparing a bionic suction cup, the bionic suction cup comprising a suction cup body and a temperature-sensitive stretchable layer disposed in the middle of the suction cup body; the preparation method includes the following steps:

[0006] 1) Dissolve acrylic acid, gelatin, AAc-NHS ester, GelMa and photoinitiator LAP in deionized water, and remove oxygen after complete dissolution to obtain DST prepolymer solution;

[0007] 2) After injecting the DST prepolymer into the mold, irradiate it with ultraviolet light for 15-30 minutes to obtain a suction cup body with a groove in the middle;

[0008] 3) Dissolve NIPAM, AAc and MBAA in deionized water, then add SDS to the mixture and heat to 70°C; after a certain time, add KPS dropwise to initiate the reaction, and collect the synthesized microgel after 4-5 hours; add EDC, HEMA and DMAP to the dispersion containing the microgel, stir the reaction mixture continuously at room temperature for 4-5 hours, then purify by dialysis with deionized water for at least 3 days, freeze-dry to obtain the product MGV and store at -20°C;

[0009] 4) Dissolve NIPAM monomer, MGV, and HEMA in water, remove oxygen with nitrogen, place in an ice bath and stir, add TEMED and stir, continue to add KPS, and inject into the groove in the middle of the suction cup body in the ice bath to form a biomimetic suction cup with a temperature-sensitive stretching layer composed of P(NIPAM-co-HEMA) material.

[0010] The NIPAM is N-isopropylacrylamide.

[0011] The AAc is acrylic acid.

[0012] The MBAA is N,N-dimethylacrylamide.

[0013] The SDS is sodium dodecyl sulfonate.

[0014] The KPS is potassium persulfate.

[0015] The EDC is 1-ethyl-(3-dimethylaminopropyl)carbodiimide.

[0016] The DMAP is 4-dimethylaminopyridine.

[0017] The HEMA is hydroxyethyl methacrylate.

[0018] The TEMED is tetramethylethylenediamine.

[0019] The photoinitiator LAP is lithium phenyl-2,4,6-trimethylbenzoyl phosphite.

[0020] The AAc-NHS ester is N-hydroxysuccinimide acrylate.

[0021] The GelMa is methacrylamide gelatin.

[0022] Preferably, in step 1), the mass percentage concentration of each component in the DST prepolymer solution is: acrylic acid 10-50%; gelatin 10-20%; AAc-NHS ester 1-5%; GelMa 0.1-0.3%; photoinitiator LAP 0.2-5%.

[0023] Preferably, both the suction cup body and the temperature-sensitive telescopic layer are circular, and the diameter ratio of the suction cup body to the temperature-sensitive telescopic layer is 5:3; the thickness of the suction cup body is 5mm, and the thickness of the temperature-sensitive telescopic layer is 2-5mm.

[0024] The beneficial effects of this invention are as follows: The bionic suction cup of this invention consists of two parts: the suction cup body and a temperature-sensitive stretchable layer disposed in the middle of the suction cup body. The suction cup body is mainly made of PAAc-NHS ester, gelatin methacrylate (GelMA), and gelatin. Because the negatively charged carboxyl groups in PAAc-NHS ester enable rapid hydration and expansion of the gel, it can dry wet surfaces within seconds under certain pressure. Furthermore, the groups within PAAc-NHS ester undergo hydrogen bonding and electrostatic interactions with the amino groups of tissues to generate adhesion to tissues. The temperature-sensitive stretchable layer possesses good temperature sensitivity, biocompatibility, tensile strength, and compressive strength. In particular, its temperature-sensitive stretchable properties make it water-soluble at physiological temperatures, but when the temperature exceeds its critical dissolution temperature, the layer shrinks, resulting in a smaller volume and thus generating negative pressure adsorption. Therefore, combining these two materials enables the suction cup to maintain good adsorption effects on wet surfaces and textured surfaces without producing toxicity or irritation. The suction cup shows promising potential for adsorption and traction of tissues and organs during surgery. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the bionic suction cup structure in Example 1.

[0026] Figure 2 The graph shows the adsorption test data of different sizes of bionic suction cups at room temperature in Example 1.

[0027] Figure 3 The graph shows the adsorption test data of different specifications of bionic suction cups in Example 1 at 37°C.

[0028] Figure 4 The graph shows the biomimetic suction cup adsorption test data at room temperature and 37°C in Example 1.

[0029] Figure 5 This is a comparison chart of the suction cup body in Example 1 and the biomimetic suction cup adsorption test data under 37°C conditions.

[0030] Figure 1 In the middle: 1. Suction cup body; 2. Temperature-sensitive stretchable layer. Detailed Implementation

[0031] The present invention will be further described in detail below with reference to specific embodiments, but the present invention is not limited to the following specific embodiments.

[0032] Example 1

[0033] like Figure 1 As shown, the bionic suction cup includes a suction cup body 1 and a temperature-sensitive stretchable layer 2 disposed in the middle of the suction cup body 1; the preparation method includes the following steps:

[0034] 1) Dissolve 10g of gelatin in 100ml of phosphate buffer solution, slowly heat to 50℃, and allow it to react completely at this temperature for 1 hour. Take 2ml of methacrylic anhydride solution and slowly add it dropwise to the above solution, continue to maintain this temperature, and allow it to react completely for 3 hours. Then add 400ml of phosphate buffer solution to stop the reaction. Take an 8000-14000kDa dialysis bag, add the above solution to the dialysis bag, and place it in deionized water for dialysis for 24 hours, changing the deionized water every 6 hours during dialysis. Dialyze for 3-5 days. After dialysis, freeze-dry the solution to obtain methacrylamide gelatin (GelMa). At room temperature, dissolve acrylic acid, gelatin, AAc-NHS ester, GelMa, and photoinitiator LAP in deionized water. The mass percentage concentrations of each component are: acrylic acid 30%; gelatin 10%; AAc-NHS ester 1%; GelMa 0.1%; photoinitiator LAP 0.2%. After complete dissolution, the DST prepolymer is injected into the mold and irradiated with ultraviolet light for 30 minutes to obtain a suction cup body with a groove in the middle.

[0035] 2) Dissolve 2.848 g NIPAM, 0.202 g AAc, and 0.064 g MBAA in 200 mL of deionized water. Then add 0.116 g SDS to the mixture and heat to 70°C. After 1 h, add 0.16 g KPS (dissolved in 4 mL of deionized water) dropwise to initiate the reaction, continuing for 4 h. Collect the synthesized microgel and purify it by dialysis with anti-deionized water for at least 3 days; the reaction formula is as follows:

[0036]

[0037] 4.78 g EDC, 3.64 g HEMA, and 0.17 g DMAP were added to 100 mL of MG microgel dispersion (containing approximately 1.5 g of microgel). The reaction mixture was stirred continuously at room temperature for 4 h. The functionalized microgel was purified by dialyzing with deionized water for at least 3 days, lyophilized, and stored at -20°C. The product was designated MGV, and the reaction formula is as follows:

[0038]

[0039] 3) Dissolve 3 mol / L NIPAM monomer, 0.2 g MGV, and 0.1 g HEMA in 10 ml of water. After deoxygenating with nitrogen for 15 min, place the solution in an ice bath and stir. Add 20 μL of TEMED and stir for 20 min. Then add 0.0042 g of KPS and quickly inject the solution into the groove in the middle of the suction cup body in an ice bath to form a temperature-sensitive stretchable layer composed of P(NIPAM-co-HEMA) material. The reaction formula is as follows:

[0040]

[0041] Thus, a biomimetic suction cup with a temperature-sensitive stretchable layer 2 in the middle was obtained.

[0042] Adsorption performance test

[0043] Production Figure 1 The bionic suction cup shown has a circular body and a temperature-sensitive stretchable layer. The tensile strength test of pigskin under different diameter-to-thickness ratios of the suction cup body (outer ring) and the temperature-sensitive stretchable layer (inner ring) is as follows: The grease on the pigskin surface is scraped off, and the suction cup is fixed in place. A 5cm diameter bionic suction cup is attached to the pigskin surface. The back of the suction cup is connected to a tensile testing machine via a wire. Tests are performed for inner-to-outer ring diameter ratios of (2:5), (3:5), and (4:5)cm, and inner-to-outer ring thickness ratios of (2:5), (3:5), and (4:5)mm. The tensile testing machine speed is adjusted to 20mm / s, and reverse stretching is performed. The test is stopped when the suction cup completely detaches from the pigskin. Each size of bionic suction cup undergoes 5 tensile tests. Figure 2 As shown, at room temperature, the bionic suction cup with an inner-to-outer diameter ratio of 3:5cm and a thickness ratio of 3:5mm has the best tensile modulus.

[0044] The grease on the surface of the pigskin was scraped off, and the pigskin was placed on a temperature-controlled clamp and secured with thread. A 5cm diameter bionic suction cup was then attached to the pigskin surface. The back of the suction cup was connected to a tensile testing machine via a thread. The ratio of the inner to outer diameter was tested at (2:5), (3:5), and (4:5) cm, and the ratio of the inner to outer thickness was tested at (2:5), (3:5), and (4:5) mm. The clamp was connected to a temperature-controlled circulator, allowing 37℃ hot water to circulate through the clamp to maintain the pigskin temperature at 37℃. The tensile testing machine was adjusted to a tension speed of 20mm / s, and reverse stretching was performed. The test was stopped when the suction cup completely detached from the pigskin. Five tensile tests were performed on each size of bionic suction cup. Figure 3-4 As shown, it was found that at 37℃ (simulating human body temperature), the bionic suction cup with an inner-to-outer diameter ratio of 3:5cm and a thickness ratio of 2:5mm has the best tensile modulus.

[0045] A suction cup with a diameter of 5cm and a thickness of 5mm (no inner ring, only outer ring) was used for testing. Each sample was tested 5 times. Figure 5 As shown, the bionic suction cup performs significantly better than the pure outer ring suction cup.

[0046] Because the suckers on the underside of an octopus can exert a strong adhesive force on most surfaces, including underwater environments, through physical action and internal negative pressure, the applicant developed this biomimetic sucker. This allows for liver suspension to expose the surgical area. By analyzing the structure of the octopus's foot, the applicant divided the biomimetic sucker into two parts: the sucker body is mainly made of polyacrylic acid grafted with n-hydroxysuccinimide ester (PAAc-NHS), gelatin methacrylate (GelMA), and gelatin. The negatively charged carboxyl groups in PAAc-NHS ester enable rapid hydration and expansion of the gel, allowing it to dry wet surfaces within seconds under certain pressure. Furthermore, the groups within PAAc-NHS ester form hydrogen bonds and electrostatic interactions with the amino groups of tissues, resulting in adhesion to the tissue. The middle of the sucker body contains a temperature-sensitive stretching layer. The thermosensitive stretching layer is composed of P(NIPAm-co-HEMA) hydrogel crosslinked with microgels. P(NIPAM-co-HEMA) is a novel hydrogel material copolymerized from N-isopropylacrylamide (NIPAM) and 2-hydroxyethyl methacrylate (HEMA). It exhibits excellent thermosensitivity and biocompatibility. Firstly, due to the thermosensitive characteristics of P(NIPAM-co-HEMA), NIPAM forms linear micelles in water and is water-soluble at physiological temperatures. However, when the temperature exceeds its critical dissolution temperature (LCST), NIPAM transforms from linear micelles into spherical micelles, and the hydrophobic portion inside the micelles shrinks inward, resulting in a smaller gel volume and smaller gel pores. Its thermosensitivity refers to this transformation characteristic. The LCST of P(NIPAM-co-HEMA) is approximately 32℃-34℃, which, compared to the LCST of NIPAM alone, provides a temperature response range more suitable for the temperature of human tissues. Secondly, the mechanical properties of P(NIPAM-co-HEMA) are superior to those of PNIPAM synthesized using the traditional crosslinking agent MBAA. Traditional PNIPAM is often crosslinked using N,N'-methylenebisacrylamide (MBAA), which can be toxic. When preparing PNIPAM hydrogels, the mechanical properties can be enhanced by adding HEMA to the PNIPAM system. One major reason is that HEMA contains a large number of crosslinked structures, giving it higher tensile and compressive strengths and enabling it to form a more stable three-dimensional network structure in water. Therefore, adding HEMA hydrogel to PNIPAM can increase its structural strength and stability, resulting in better performance in applications. Furthermore, the presence of HEMA in the system can also improve the temperature responsiveness and water absorption properties of the PNIPAM hydrogel.In addition, P(NIPAM-co-HEMA) also has good biocompatibility. Both NIPAM and HEMA are biocompatible materials that do not produce toxicity or irritation when in contact with the human body.

[0047] The above are merely exemplary embodiments of the present invention and do not constitute any limitation on the scope of protection of the present invention. All technical solutions formed by equivalent exchange or substitution fall within the scope of protection of the present invention.

Claims

1. A method for preparing a biomimetic suction cup, characterized in that, The biomimetic suction cup includes a suction cup body and a temperature-sensitive stretchable layer disposed in the middle of the suction cup body; the preparation method includes the following steps: 1) Dissolve acrylic acid, gelatin, AAc-NHS ester, GelMa and photoinitiator LAP in deionized water, and remove oxygen after complete dissolution to obtain DST prepolymer solution; 2) After injecting the DST prepolymer into the mold, irradiate it with ultraviolet light for 15-30 minutes to obtain a suction cup body with a groove in the middle; 3) Dissolve NIPAM, AAc, and MBAA in deionized water, then add SDS to the mixture and heat to 70°C; after a certain time, add KPS dropwise to initiate the reaction, and collect the synthesized microgel after 4-5 hours; add EDC, HEMA, and DMAP to the dispersion containing the microgel, stir the reaction mixture continuously at room temperature for 4-5 hours, then purify by dialysis with deionized water for at least 3 days, freeze-dry to obtain the product MGV and store at -20°C; 4) Dissolve NIPAM monomer, MGV, and HEMA in water, remove oxygen with nitrogen, place in an ice bath and stir, add TEMED and stir, continue to add KPS, and inject into the groove in the middle of the suction cup body in the ice bath to form a biomimetic suction cup with a temperature-sensitive stretching layer composed of P (NIPAM-co-HEMA) material. In step 1), the mass percentage concentration of each component in the DST prepolymer solution is as follows: acrylic acid 10-50%; gelatin 10-20%; AAc-NHS ester 1-5%; GelMa 0.1-0.3%; photoinitiator LAP 0.2-5%; Both the suction cup body and the temperature-sensitive telescopic layer are circular, with a diameter ratio of 5:3 between the suction cup body and the temperature-sensitive telescopic layer; the suction cup body has a thickness of 5mm, and the temperature-sensitive telescopic layer has a thickness of 2-5mm.

2. The method for preparing the bionic suction cup according to claim 1, characterized in that, The NIPAM is N-isopropylacrylamide, the AAc is acrylic acid, and the MABAA is N,N-dimethylacrylamide.

3. The method for preparing the bionic suction cup according to claim 1, characterized in that, The SDS is sodium dodecyl sulfonate.

4. The method for preparing the bionic suction cup according to claim 1, characterized in that, The KPS mentioned is potassium persulfate.

5. The method for preparing the bionic suction cup according to claim 1, characterized in that, The EDC is 1-ethyl-(3-dimethylaminopropyl)carbodiimide.

6. The method for preparing the bionic suction cup according to claim 1, characterized in that, The DMAP is 4-dimethylaminopyridine, the HEMA is hydroxyethyl methacrylate, and the TEMED is tetramethylethylenediamine.

7. The method for preparing the bionic suction cup according to claim 1, characterized in that, The photoinitiator LAP is lithium phenyl-2,4,6-trimethylbenzoyl phosphite.

8. The method for preparing the bionic suction cup according to claim 1, characterized in that, The AAc-NHS ester is N-hydroxysuccinimide acrylate, and the GelMa is methacrylamide gelatin.

Images