Hydrogel patch capable of resisting suture tearing as well as preparation method and application of hydrogel patch

Abstract

The invention relates to the technical field of biological materials, in particular to a suture-tear-resistant hydrogel patch, a preparation method and application of the suture-tear-resistant hydrogel patch, the hydrogel operation patch adopts double-crosslinking polyvinyl alcohol (PVA) hydrogel, PVA molecular chain conformation is optimized in a solution casting and annealing mode, and then a permanent reversible crosslinking domain (nanocrystal domain) is introduced. And then, tannic acid is introduced as a dynamic cross-linking agent to form an instantaneous reversible cross-linking domain, so that the energy density of the defect tip is improved, and the mechanical strength of the patch is enhanced. In the suturing process, the patch can effectively resist tearing caused by sutures, and deformation under external mechanical loads is avoided. The hydrogel operation patch provided by the invention can reduce tissue adhesion and improve long-term stability, and is suitable for biomedical application such as abdominal wall repair and rotator cuff tear repair.

Description

Technical Field

[0001] The present invention relates to the technical field of biomaterials, and particularly relates to a hydrogel patch resistant to suture tearing, a preparation method thereof, and an application thereof. Background Art

[0002] As an important biomedical material, surgical patches are widely used in soft tissue repair surgeries such as abdominal wall defects and rotator cuff tears, aiming to promote tissue healing and restore its function. With the continuous development of medical technology, the design and application of surgical patches have shifted from traditional single functions to multifunctional intelligent repair materials. However, existing surgical patches still face some challenges in practical applications, especially being prone to mechanical stimulation or tearing during the suture process and easily causing complications such as tissue adhesion.

[0003] Traditional surgical patches, especially mesh patches, inevitably suffer from defects caused by sutures during the suture process. These defects are prone to cause stress concentration when the patch bears repeated mechanical loads, resulting in tearing or deformation of the patch, thereby affecting the repair effect and even potentially leading to treatment failure. Especially in the fields of abdominal wall defect repair and rotator cuff tear repair, the tearing of the patch may directly affect tissue recovery and increase the pain of patients.

[0004] Although the mesh-structured patch enhances the mechanical properties of the patch to a certain extent, its porous structure often becomes a "hotbed" for tissue adhesion. Adhesion between the patch and surrounding tissues may cause complications such as intestinal obstruction, chronic pain, and infection. Therefore, how to avoid tissue adhesion while ensuring good mechanical properties of the patch is an important topic in the research and development of surgical patches.

[0005] Biocompatibility and long-term stability: Most of the materials of existing surgical patches are synthetic polymer materials such as polypropylene and polyurethane. These materials are prone to degradation or performance decline after long-term implantation in the body, resulting in patch failure. Especially when bearing biological loads or external pressures for a long time, the patch may gradually become fragile, thus affecting its long-term stability and repair effect.

[0006] Currently, in the research on surgical patches, some technical solutions have attempted to solve the above problems, but there are still certain limitations.

[0007] Chinese Patent Application CN202410122070.8 discloses a polypropylene patch loaded with silver nanoparticles. This patch uses polypropylene as the substrate and endows the patch with certain antibacterial properties through surface treatment and silver nanoparticle plating. Although this patch has made breakthroughs in antibacterial properties, its mechanical properties are still limited by the polypropylene material itself. Especially under long-term loading, the polypropylene patch is prone to deformation or failure, and its mesh structure is prone to cause tissue adhesion, increasing the risk of postoperative complications.

[0008] Chinese invention patent application CN202311381622.9 discloses a polyvinyl alcohol (PVA) / alginate composite material. This solution uses PVA and sodium alginate (SA) / polyvinyl alcohol (PVA) / chitosan quaternary ammonium salt (HACC) composite materials for abdominal wall repair. The composite material can provide a certain tensile strength during the suturing process and reduce tissue adhesion during the repair process. However, the defect of this solution is that the fatigue resistance test under suturing is not carried out, and the patch may fail when subjected to mechanical loads for a long time, especially under cyclic loads. There is still a certain risk of failure.

[0009] Based on the traditional mesh patch, some researchers have tried to improve the antibacterial properties of the patch by nanosilver coating. However, these solutions still fail to effectively solve the tissue adhesion problem caused by the mesh structure, and the polypropylene-based material will deform due to external cyclic loads during long-term use, which may cause the patch to fail. Therefore, although these modification technologies can improve the performance of the patch to a certain extent, they still do not solve the defects introduced by sutures and the problem of long-term stability.

[0010] In previous studies, researchers only mentioned that PVA was simply cross-linked with tannic acid to improve the mechanical properties of PVA hydrogels. However, other studies have ignored the interaction between the transient reversible cross-linked domains constructed by the introduction of tannic acid, a polyhydroxy compound, and the permanent reversible cross-linked domains in the PVA molecules. Moreover, there is still a lack of research on the microscopic explanation of the synergistic effect of tannic acid and PVA nanocrystal domains on the overall resistance of hydrogels to suture tearing. At the same time, the effects of PVA annealing time and the concentration of tannic acid soaking on the hydrogel patch are unknown.

[0011] In view of the above-mentioned defects, the inventors of the present invention finally obtained the present invention after a long period of research and practice. Summary of the invention

[0012] The purpose of the present invention is to solve the problem that the mesh structure of the mesh patch causes tissue adhesion, and the polypropylene-based material may deform due to external cyclic loads during long-term use, which may cause the patch to fail. A hydrogel patch that resists suture tearing, a preparation method and its application are provided.

[0013] In order to achieve the above object, the present invention discloses a method for preparing a hydrogel patch resistant to suture tearing, comprising the following steps:

[0014] S1, dissolving PVA powder in deionized water to obtain a PVA solution;

[0015] S2, injecting the PVA solution obtained in step S1 into a mold, drying and hot pressing into a PVA film;

[0016] S3. Immerse the PVA film after hot pressing into a film in a crosslinking agent solution for crosslinking treatment, and swell and equilibrate in deionized water to obtain a hydrogel patch.

[0017] In the step S1, the concentration of the PVA solution is 5 wt% - 20 wt%.

[0018] In the step S2, the PVA solution is first degassed in a rotary degassing machine for 5 min.

[0019] In the step S2, the hot pressing temperature of the PVA film is 80°C - 160°C, the hot pressing pressure is 1 MPa - 5 MPa, and the hot pressing time is 5 min - 60 min.

[0020] In the step S3, the crosslinking agent is a compound for dynamic crosslinking with tannic acid, and the concentration of the crosslinking agent is 5 wt% - 30 wt%.

[0021] In the step S3, the PVA film is soaked in the crosslinking agent for 48 h and swells and equilibrates in deionized water for 72 h.

[0022] The present invention also discloses a hydrogel patch resistant to suture tearing prepared by the above preparation method and the application of such a hydrogel patch resistant to suture tearing in the field of soft tissue repair.

[0023] The present invention prepares a hydrogel patch resistant to suture tearing by introducing two non-covalent interactions of a permanent reversible crosslinking domain and an instantaneous reversible crosslinking domain. In the face of a load, the stress at the crack tip of the hydrogel patch can be transmitted to the rigid permanent reversible crosslinking domain (nanocrystalline domain) through the instantaneous reversible crosslinking domain, and then the rigid nanocrystalline domain disperses the stress in a larger range of amorphous matrix. The crack tip is passivated, the area of the crack propagation process is increased, and finally the suture tearing resistance performance of the hydrogel patch is increased.

[0024] The beneficial effects of the present invention compared with the prior art are as follows:

[0025] 1. The hydrogel surgical patch resistant to suture tearing of the present invention combines double crosslinking technology, antibacterial treatment and tissue adhesion prevention functions, can not only effectively resist tearing caused by sutures, but also reduce the occurrence of postoperative complications, provide better treatment effects, and is widely applied to abdominal wall repair, rotator cuff tear repair and others;

[0026] 2. The present invention makes the reversible crosslinking domain and the instantaneous reversible crosslinking domain cooperate to resist the crack propagation in soft tissue repair surgery by regulating the PVA annealing temperature and the concentration of the soaked tannic acid solution. Description of the Drawings

[0027] Figure 1 Schematic diagram for the preparation of the double-crosslinked PVA hydrogel patch in Example 1;

[0028] Figure 2 Suture performance demonstration diagram of the double-crosslinked PVA hydrogel patch in Example 1;

[0029] Figure 3 Tear resistance performance demonstration diagram of the double-crosslinked PVA hydrogel patch in Example 1;

[0030] Figure 4 Transmission electron microscope micrograph of Example 1;

[0031] Figure 5 Uniaxial tensile stress-strain diagrams of Example 1 and Comparative Examples 1, 2, 3, 4, and 5;

[0032] Figure 6 Tensile strain of Example 1 and Comparative Examples 1, 2, 3, 4, and 5

[0033] Figure 7 Statistical chart of fracture work of Example 1 and Comparative Examples 1, 2, 3, 4, and 5;

[0034] Figure 8 Antibacterial performance demonstration diagram of Example 1 and Comparative Example 3.

[0035] Figure 9 Anti-adhesion effect demonstration of Example 1 and commercial products in the repair of rat abdominal wall defects. Detailed implementation method

[0036] The following further elaborates on the above and additional technical features and advantages of the present invention with reference to the accompanying drawings.

[0037] Example 1

[0038] Mix 10 g of PVA powder with 90 mL of deionized water, and mechanically stir at 100 °C for 8 hours to prepare a 10% PVA solution;

[0039] Inject the above PVA solution into a mold and dry it in a drying oven at 40 °C for 24 hours;

[0040] Hot press the formed PVA film on a hot press at 140 °C and 2 MPa for 30 min to obtain the hot-pressed PVA film;

[0041] Take 20 g of tannic acid and add it to 80 mL of deionized water, and stir under ultrasonic for 2 hours to prepare a 20% tannic acid solution;

[0042] Immerse the hot-pressed PVA film in the 20% tannic acid solution for 48 hours, and then soak it in deionized water for 72 hours to wash away the excess tannic acid to obtain a double-crosslinked PVA hydrogel (named BFT).

[0043] Under the conditions of Example 1, the BFT hydrogel patch demonstrated excellent suture ability. As Figure 2 shown, the BFT hydrogel patch was sutured onto porcine ex vivo muscle tissue and remained intact and adhered to the muscle tissue after folding and twisting. Additionally, Figure 3 showed the strong anti-suture tear ability of the BFT patch, with the sutured area remaining intact under the pull of a 1 kg weight. After annealing and soaking in tannic acid, scanning electron microscope images showed that the surface of the BFT hydrogel patch was distributed with dense pores. The BFT hydrogel patch had a strength of 60.17 MPa, a fracture strain of 503.97%, and a fracture work of 108.15 MJ / m 3 , indicating its excellent mechanical properties. Further, Figure 8 showed that the BFT patch had excellent antibacterial ability against Staphylococcus aureus and Clostridium perfringens. Figure 9 Evaluated the anti-adhesion effect in the repair of rat abdominal wall defects. Digital photos showed that the BFT patch treatment group had excellent anti-adhesion ability in the treatment of rat abdominal wall defects. It demonstrated the great potential of the BFT patch in the treatment of abdominal wall defects.

[0044] Comparative Example 1

[0045] 10 g of PVA powder was mixed with 90 mL of deionized water and mechanically stirred at 100 °C for 8 hours to prepare a 10% PVA solution;

[0046] The above PVA solution was poured into a mold and dried in a drying oven at 40 °C for 24 hours;

[0047] The formed PVA film was hot-pressed on a hot press at 140 °C and 2 MPa for 30 min to obtain the hot-pressed PVA film;

[0048] The hot-pressed PVA film was soaked in deionized water to obtain a 140 °C annealed PVA hydrogel (named HC).

[0049] Under the conditions of Comparative Example 1, HC had a strength of 29.27 MPa, a fracture strain of 488.10%, and a fracture work of 62.78 MJ / m 3 .

[0050] Comparative Example 2

[0051] 10 g of PVA powder was mixed with 90 mL of deionized water and mechanically stirred at 100 °C for 8 hours to prepare a 10% PVA solution;

[0052] The above PVA solution was poured into a mold and dried in a drying oven at 40 °C for 24 hours;

[0053] The formed PVA film was hot-pressed on a hot press at 80 °C and 2 MPa for 30 min to obtain the hot-pressed PVA film;

[0054] The hot-pressed PVA film was soaked in deionized water to obtain an 80 °C annealed PVA hydrogel (named LC).

[0055] Under the conditions of Comparative Example 2, LC had a strength of 14.66 MPa, a fracture strain of 428.59%, and a fracture energy of 18.50 MJ / m 3 .

[0056] Comparative Example 3

[0057] 10 g of PVA powder was mixed with 90 mL of deionized water and mechanically stirred at 100 °C for 8 hours to prepare a 10% PVA solution;

[0058] The above PVA solution was poured into a mold and dried in an oven at 40 °C for 24 hours;

[0059] The formed PVA film was soaked in deionized water to obtain a PVA hydrogel (named Pristine).

[0060] Under the conditions of Comparative Example 3, Pristine had a strength of 6.11 MPa, a fracture strain of 349.79%, and a fracture energy of 8.19 MJ / m 3 . At the same time, Figure 8 it was shown that Pristine did not have antibacterial ability against Staphylococcus aureus and Clostridium perfringens.

[0061] Comparative Example 4

[0062] 10 g of PVA powder was mixed with 90 mL of deionized water and mechanically stirred at 100 °C for 8 hours to prepare a 10% PVA solution;

[0063] The above PVA solution was poured into a mold and dried in an oven at 40 °C for 24 hours;

[0064] The formed PVA film was hot-pressed on a hot press at 140 °C and 2 MPa for 30 min to obtain the hot-pressed PVA film;

[0065] 10 g of tannic acid was added to 80 mL of deionized water and stirred under ultrasonic for 2 hours to prepare a 10% tannic acid solution;

[0066] The hot-pressed PVA film was immersed in the 10% tannic acid solution for 48 hours, and then soaked in deionized water for 72 hours to wash away the excess tannic acid, obtaining a double-crosslinked PVA hydrogel (named HC-TA 10％ ).

[0067] Under the conditions of Comparative Example 4, HC-TA 10％ has a strength of 46.14 MPa, a fracture strain of 463.47%, and 76.87 MJ / m 3 of fracture work.

[0068] Comparative Example 5

[0069] Mix 10 g of PVA powder with 90 mL of deionized water and mechanically stir at 100 °C for 8 hours to prepare a 10% PVA solution;

[0070] Inject the above PVA solution into a mold and dry it in a drying oven at 40 °C for 24 hours;

[0071] Hot press the formed PVA film on a hot press at 110 °C and 2 MPa for 30 min to obtain a hot-pressed PVA film;

[0072] Take 20 g of tannic acid and add it to 80 mL of deionized water, stir under ultrasonic for 2 hours to prepare a 20% tannic acid solution;

[0073] Immerse the hot-pressed PVA film in the 20% tannic acid solution for 48 hours, then soak it in deionized water for 72 hours to wash away the excess tannic acid, and obtain a double-crosslinked PVA hydrogel (named PVA 110℃ -TA 20％ ).

[0074] Under the conditions of Comparative Example 5, PVA 110℃ -TA 20％ has a strength of 20.35 MPa, a fracture strain of 438.99%, and 28.82 MJ / m 3 of fracture work.

[0075]

[0076] The above are only the preferred embodiments of the present invention, which are illustrative rather than restrictive to the present invention. Those skilled in the art understand that many changes, modifications, and even equivalents can be made within the spirit and scope defined by the claims of the present invention, but all will fall within the protection scope of the present invention.

Claims

1. A method for preparing a hydrogel patch resistant to suture tearing, characterized in that: The following steps are involved: S1, dissolving PVA powder in deionized water to obtain a PVA solution; S2, injecting the PVA solution obtained in step S1 into a mold, drying and hot pressing into a PVA film; S3, immersing the PVA film formed by hot pressing in step S2 into a crosslinking agent solution for crosslinking treatment, and achieving swelling equilibrium in deionized water to obtain a hydrogel patch.

2. The method for preparing a suture tear resistant hydrogel patch according to claim 1, characterized in that: In the step S1, the concentration of the PVA solution is 5wt% to 20wt%.

3. The method for preparing a suture tear resistant hydrogel patch according to claim 1, characterized in that: In step S2, the PVA solution is first degassed in a rotary degasser for 5 minutes.

4. The method for preparing a suture tear resistant hydrogel patch according to claim 1, characterized in that: In the step S2, the hot pressing temperature of the PVA film is 80°C to 140°C, the hot pressing pressure is 1MPa to 5MPa, and the hot pressing time is 5min to 60min.

5. The method for preparing a suture tear resistant hydrogel patch according to claim 1, characterized in that: In the step S3, the cross-linking agent is a compound that is dynamically cross-linked by tannic acid, and the concentration of the cross-linking agent is 10wt% to 20wt%.

6. The method for preparing a suture tear resistant hydrogel patch according to claim 1, characterized in that: In step S3, the PVA film is immersed in the cross-linking agent for 48 hours and swells in deionized water for 72 hours.

7. A suture tear resistant hydrogel patch using the suture tear resistant hydrogel patch according to any one of claims 1 to 6.

8. Use of the suture tear-resistant hydrogel patch according to claim 7 in the field of soft tissue repair.

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