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Open AccessOpen Access JUSTC Life Sciences；Engineering & Materials 01 April 2024

Highly transparent and strong nanohesive hydrogel patch for tissue adhesion

  • 1.

    College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China

  • 2.

    Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310018, China

  • 3.

    School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009, China

  • 4.

    College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China

  • 5.

    Department of General Surgery, Anhui No.2 Provincial People’s Hospital, Hefei 230601, China

Cite this:
https://doi.org/10.52396/JUSTC-2023-0143
More Information
  • Author Bio:

    Qing Luo is currently pursuing a master’s degree at the School of Materials Science and Engineering, Zhejiang University of Technology. Her research mainly focuses on the functional design of biomimetic materials and nanoadhesives

    Dong-Quan Liu received his master’s degree in Clinical Medicine (Surgery) from Chongging Medical University in 2016. He is currently working in the Department of Hepatobiliary Surgery at Anhui No.2 Provincial People’s Hospital. His primary research focuses on liver cancer

    Liang Dong received his Ph.D. degree in Biomaterials from the University of Science and Technology of China in 2014. He is currently a researcher at the Hangzhou Institute of Medicine, Chinese Academy of Sciences. His primary research focuses on designing functional biomimetic biomaterials and exploring their biomedical applications, which include tumor treatment, tissue repair, imaging diagnosis, and immunoregulation

  • Corresponding author: E-mail: totoro91@foxmail.com; E-mail: dongliang@him.cas.cn
  • Received Date: 29 September 2023
  • Accepted Date: 26 February 2024
    • Available Online: 01 April 2024
    Abstract

  • Abstract

    This research aimed to design and fabricate a biocompatible dual-layer chitosan hydrogel adhesive patch with exceptional mechanical properties by employing a nanoadhesive strategy to assess its tissue adhesion performance. The design involves physical cross-linking to construct a robust chitosan hydrogel as a backing membrane, followed by in situ photocuring to create the adhesive hydrogel layer, resulting in an integrated chitosan hydrogel adhesive patch. To facilitate adhesion between the hydrogel patch and biological tissue, surface-activated silica nanoparticles serve as interfacial connectors, analogous to nanoglue, promoting binding of the hydrogel to the substrate. Characterization of the patch reveals an adhesive energy of 282 J/m2 to biological tissues in vitro and a burst pressure of 450 mmHg (1 mmHg=0.133 kPa). The patch exhibits outstanding mechanical properties, with a tensile strength of 4.3 MPa, an elongation rate of 65%, and a fracture toughness of 3.82 kJ/m2. Additionally, the nanohesion-based chitosan hydrogel adhesive patch is highly transparent and demonstrates excellent biocompatibility. It holds promise for applications in various biomedical fields, including tissue repair and drug delivery, thereby providing a robust material foundation for advancements in clinical surgery.

    Graphical abstract

    With the aid of a nanoadhesive strategy, a dual-layer chitosan hydrogel adhesive patch demonstrated excellent tissue wound adhesion capability.

    Abstract

    This research aimed to design and fabricate a biocompatible dual-layer chitosan hydrogel adhesive patch with exceptional mechanical properties by employing a nanoadhesive strategy to assess its tissue adhesion performance. The design involves physical cross-linking to construct a robust chitosan hydrogel as a backing membrane, followed by in situ photocuring to create the adhesive hydrogel layer, resulting in an integrated chitosan hydrogel adhesive patch. To facilitate adhesion between the hydrogel patch and biological tissue, surface-activated silica nanoparticles serve as interfacial connectors, analogous to nanoglue, promoting binding of the hydrogel to the substrate. Characterization of the patch reveals an adhesive energy of 282 J/m2 to biological tissues in vitro and a burst pressure of 450 mmHg (1 mmHg=0.133 kPa). The patch exhibits outstanding mechanical properties, with a tensile strength of 4.3 MPa, an elongation rate of 65%, and a fracture toughness of 3.82 kJ/m2. Additionally, the nanohesion-based chitosan hydrogel adhesive patch is highly transparent and demonstrates excellent biocompatibility. It holds promise for applications in various biomedical fields, including tissue repair and drug delivery, thereby providing a robust material foundation for advancements in clinical surgery.

    • Public Summary

    • A transparent chitosan hydrogel patch with excellent adhesion, mechanical properties, and biocompatibility was prepared.
    • The tensile stress, elongation at break, toughness, maximum strength, and fracture toughness all increase with increasing thickness of the chitosan hydrogel.
    • The hydrogel patch demonstrates excellent tissue wound adhesion capability.

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    • References(27)
  • [1]
    Wang S Y, Liu J Y, Wang L C, et al. Underwater adhesion and anti-swelling hydrogels. Advanced MaterialsTechnologies, 2023, 8 (6): 2201477. doi: 10.1002/admt.202201477
    [2]
    Liu X, Liu J, Lin S, et al. Hydrogel machines. Materials Today, 2020, 36: 102–124. doi: 10.1016/j.mattod.2019.12.026
    [3]
    Yang D Y. Recent advances in hydrogels. Chemistry of Materials, 2022, 34 (5): 1987–1989. doi: 10.1021/acs.chemmater.2c00188
    [4]
    Yang J, Yu H J, Wang L, et al. Advances in adhesive hydrogels for tissue engineering. European Polymer Journal, 2022, 172: 111241. doi: 10.1016/j.eurpolymj.2022.111241
    [5]
    Du X C, Liu Y J, Yan H Y, et al. Anti-infective and pro-coagulant chitosan-based hydrogel tissue adhesive for sutureless wound closure. Biomacromolecules, 2020, 21 (3): 1243–1253. doi: 10.1021/acs.biomac.9b01707
    [6]
    Salzlechner C, Haghighi T, Huebscher I, et al. Adhesive hydrogels for maxillofacial tissue regeneration using minimally invasive procedures. Advanced Healthcare Materials, 2020, 9 (4): 1901134. doi: 10.1002/adhm.201901134
    [7]
    Shen C, LI Y J, Meng Q. Adhesive polyethylene glycol-based hydrogel patch for tissue repair. Colloids and Surfaces B: Biointerfaces, 2022, 218: 112751. doi: 10.1016/j.colsurfb.2022.112751
    [8]
    Liu R X, Li Y B, Chen J C, et al. The preparation of multifunction chitosan adhesive hydrogel by “one-step” method. Journal of Biomaterials Science, Polymer Edition, 2020, 31 (15): 1925–1940. doi: 10.1080/09205063.2020.1783595
    [9]
    Qi P, Zheng Y G, Ohta S, et al. In situ fabrication of double-layered hydrogels via spray processes to prevent postoperative peritoneal adhesion. ACS Biomaterials Science & Engineering, 2019, 5 (9): 4790–4798. doi: 10.1021/acsbiomaterials.9b00791
    [10]
    Luneva O, Olekhnovich R, Uspenskaya M. Bilayer hydrogels for wound dressing and tissue engineering. Polymers, 2022, 14 (15): 3135. doi: 10.3390/polym14153135
    [11]
    Tang L, Xu Y, Liu F, et al. Synchronous ultraviolet polymerization strategy to improve the interfacial toughness of bilayer hydrogel actuators. Macromolecules, 2023, 56 (16): 6199–6207. doi: 10.1021/acs.macromol.3c00419
    [12]
    Chen Q, Zhang X Y, Chen K, et al. Bilayer hydrogels with low friction and high load-bearing capacity by mimicking the oriented hierarchical structure of cartilage. ACS Applied Materials & Interfaces, 2022, 14 (46): 52347–52358. doi: 10.1021/acsami.2c13641
    [13]
    Liu J Z, Miao J K, Zhao L, et al. Versatile bilayer hydrogel for wound dressing through PET-RAFT polymerization. Biomacromolecules, 2022, 23 (3): 1112–1123. doi: 10.1021/acs.biomac.1c01428
    [14]
    Peng W, Liu C, Lai Y J, et al. An adhesive/anti-adhesive Janus tissue patch for efficient closure of bleeding tissue with inhibited postoperative adhesion. Advanced Science, 2023, 10 (21): 2301427. doi: 10.1002/advs.202301427
    [15]
    Yao H, Wang C C, Zhang Y C, et al. Manufacture of bilayered composite hydrogels with strong, elastic, and tough properties for osteochondral repair applications. Biomimetics, 2023, 8 (2): 203. doi: 10.3390/biomimetics8020203
    [16]
    Li Y, Fu R Z, Duan Z G, et al. Mussel-inspired adhesive bilayer hydrogels for bacteria-infected wound healing via NIR-enhanced nanozyme therapy. Colloids and Surfaces B: Biointerfaces, 2022, 210: 112230. doi: 10.1016/j.colsurfb.2021.112230
    [17]
    Peers S, Montembault A, Ladavière C. Chitosan hydrogels for sustained drug delivery. Journal of Controlled Release, 2020, 326: 150–163. doi: 10.1016/j.jconrel.2020.06.012
    [18]
    Sapru S, Das S, Mandal M, et al. Sericin-chitosan-glycosamino glycans hydrogels incorporated with growth factors for in vitro and in vivo skin repair. Carbohydrate Polymers, 2021, 258: 117717. doi: 10.1016/j.carbpol.2021.117717
    [19]
    Liu F L, Wang L, Zhai X R, et al. A multi-functional double cross-linked chitosan hydrogel with tunable mechanical and antibacterial properties for skin wound dressing. Carbohydrate Polymers, 2023, 322: 121344. doi: 10.1016/j.carbpol.2023.121344
    [20]
    Nakan U, Bieerkehazhi S, Tolkyn B, et al. Synthesis, characterization and antibacterial application of copolymers based on N,N-dimethyl acrylamide and acrylic acid. Materials, 2021, 14 (20): 6191. doi: 10.3390/ma14206191
    [21]
    Bai C Z, Huang Q H, Zhang X, et al. Mechanical strengths of hydrogels of poly( N,N-dimethylacrylamide)/alginate with IPN and poly( N,N-dimethylacrylamide)/chitosan with semi-IPN microstructures. Macromolecular Materials and Engineering, 2019, 304 (11): 1900309. doi: 10.1002/mame.201900309
    [22]
    Bashir S, Hina M, Ramesh S, et al. Flexible and self-healable poly( N,N-dimethylacrylamide) hydrogels for supercapacitor prototype. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2021, 617: 126377. doi: 10.1016/j.colsurfa.2021.126377
    [23]
    Suresh D, Suresh A, Kannan R. Engineering biomolecular systems: Controlling the self-assembly of gelatin to form ultra-small bioactive nanomaterials. Bioactive Materials, 2022, 18: 321–336. doi: 10.1016/j.bioactmat.2022.02.035
    [24]
    Yan J, Li S Q, Chen G P, et al. Formation, physicochemical properties, and comparison of heat- and enzyme-induced whey protein-gelatin composite hydrogels. Food Hydrocolloids, 2023, 137: 108384. doi: 10.1016/j.foodhyd.2022.108384
    [25]
    Yuan X M, Zhu Z, Xia P C, et al. Tough gelatin hydrogel for tissue engineering. Advanced Science, 2023, 10 (24): 2301665. doi: 10.1002/advs.202301665
    [26]
    Pan Z, Fu Q Q, Wang M H, et al. Designing nanohesives for rapid, universal, and robust hydrogel adhesion. Nature Communications, 2023, 14 (1): 5378. doi: 10.1038/s41467-023-40753-5
    [27]
    Weber M, Steinle H, Golombek S, et al. Blood-contacting biomaterials: in vitro evaluation of the hemocompatibility. Frontiers in Bioengineering and Biotechnology, 2018, 6: 99. doi: 10.3389/fbioe.2018.00099
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    Figure  1.  Design and fabrication of chitosan hydrogel adhesive patches. (a) Schematic of the fabrication and application process for nanohesion-based chitosan hydrogel adhesive patches. (b) Chitosan hydrogel sample. (c) Ultraviolet crosslinking. (d) Sample of chitosan hydrogel adhesive patch. (e) Demonstration of nanohesion to porcine muscle by a chitosan hydrogel adhesive patch.

    Figure  2.  Characterization of ANP and chitosan hydrogel. (a) TEM image of ANP. (b) The distribution of hydrodynamic sizes of ANP measured by DLS. (c) Zeta potential of ANP. (d) Stress‒strain diagram of the chitosan hydrogel. (e) Maximum tensile stress of the chitosan hydrogel. (f) Elongation at break of the chitosan hydrogel. (g) The toughness of the chitosan hydrogel. (h) Swelling rate of the chitosan hydrogel. (i) Young’s modulus of the chitosan hydrogel. The values represent the means ± SDs (n = 3). The statistical significance was determined using one-way ANOVA; ns, not significant; *, P < 0.05; **, P ≤ 0.01.

    Figure  3.  Characterization of the adhesive properties of the chitosan hydrogel adhesive patch. (a) Adhesion of the chitosan hydrogel adhesive patch to porcine liver tissue. (b) Adhesion of the chitosan hydrogel adhesive patch to porcine heart tissue. (c) Schematic illustration of the 180° peeling test and burst pressure test. (d) Interfacial toughness of the adhesive layer at different gelatin contents. (e) Interfacial toughness of chitosan hydrogel adhesive patches with different thicknesses on various adherent substrates. (f) Burst pressure tolerance of chitosan hydrogel adhesive patches with different thicknesses. The values represent the means ± SDs (n = 3). The statistical significance was determined using the t test and one-way ANOVA; ns, not significant; *, P < 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.

    Figure  4.  Mechanical properties of the chitosan hydrogel adhesive patch. (a) Stress‒strain diagram of the chitosan hydrogel adhesive patch. (b) Maximum tensile stress of the chitosan hydrogel adhesive patch. (c) Elongation at break of the chitosan hydrogel adhesive patch. (d) Young’s modulus of the chitosan hydrogel adhesive patch. (e) Toughness of the chitosan hydrogel adhesive patch. (f) Maximum load of the chitosan hydrogel adhesive patch. (g) Diagram of a method used to measure and calculate the work of fracture and fracture toughness. (h) Fracture toughness of the chitosan hydrogel adhesive patch. (i) Transmittance of the chitosan hydrogel adhesive patch. (j) Transmittance of the chitosan hydrogel adhesive patch at 550 nm (n=9). (k) Microstructure of the chitosan hydrogel adhesive patch and a picture of the real product. The values represent the means ± SDs (n = 3). The statistical significance was determined using one-way ANOVA; ns, not significant; *, P < 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.

    Figure  5.  Biocompatibility and cytotoxicity studies. (a, b) OD value and cell viability analysis within 7 d by CCK-8 assay. (c) Live/dead staining images of cells cultured in the hydrogel and control groups after 7 d; scale bar: 100 µm. The values represent the means ± SDs (n = 3). The statistical significance was determined using one-way ANOVA; ns, not significant; ***, P ≤ 0.001.

    Figure  6.  In vivo biocompatibility. (a, b) Hemolysis rates and corresponding images of different materials, with NS indicating normal saline. (c) Rat subcutaneous inflammation model. (d) Macroscopic images of subcutaneous samples from rats. (e) Fibrous capsule thickness around the implanted samples after in vivo implantation. (f) Histological images were stained with HE and Masson’s trichrome at 14 d for CS and C-PDMA, with * representing implant CS and + representing implant C-PDMA. The values represent the means ± SDs (n = 3). The statistical significance was determined using the t test and one-way ANOVA; ns, not significant; **, P ≤ 0.01; ***, P ≤ 0.001.

    [1]
    Wang S Y, Liu J Y, Wang L C, et al. Underwater adhesion and anti-swelling hydrogels. Advanced MaterialsTechnologies, 2023, 8 (6): 2201477. doi: 10.1002/admt.202201477
    [2]
    Liu X, Liu J, Lin S, et al. Hydrogel machines. Materials Today, 2020, 36: 102–124. doi: 10.1016/j.mattod.2019.12.026
    [3]
    Yang D Y. Recent advances in hydrogels. Chemistry of Materials, 2022, 34 (5): 1987–1989. doi: 10.1021/acs.chemmater.2c00188
    [4]
    Yang J, Yu H J, Wang L, et al. Advances in adhesive hydrogels for tissue engineering. European Polymer Journal, 2022, 172: 111241. doi: 10.1016/j.eurpolymj.2022.111241
    [5]
    Du X C, Liu Y J, Yan H Y, et al. Anti-infective and pro-coagulant chitosan-based hydrogel tissue adhesive for sutureless wound closure. Biomacromolecules, 2020, 21 (3): 1243–1253. doi: 10.1021/acs.biomac.9b01707
    [6]
    Salzlechner C, Haghighi T, Huebscher I, et al. Adhesive hydrogels for maxillofacial tissue regeneration using minimally invasive procedures. Advanced Healthcare Materials, 2020, 9 (4): 1901134. doi: 10.1002/adhm.201901134
    [7]
    Shen C, LI Y J, Meng Q. Adhesive polyethylene glycol-based hydrogel patch for tissue repair. Colloids and Surfaces B: Biointerfaces, 2022, 218: 112751. doi: 10.1016/j.colsurfb.2022.112751
    [8]
    Liu R X, Li Y B, Chen J C, et al. The preparation of multifunction chitosan adhesive hydrogel by “one-step” method. Journal of Biomaterials Science, Polymer Edition, 2020, 31 (15): 1925–1940. doi: 10.1080/09205063.2020.1783595
    [9]
    Qi P, Zheng Y G, Ohta S, et al. In situ fabrication of double-layered hydrogels via spray processes to prevent postoperative peritoneal adhesion. ACS Biomaterials Science & Engineering, 2019, 5 (9): 4790–4798. doi: 10.1021/acsbiomaterials.9b00791
    [10]
    Luneva O, Olekhnovich R, Uspenskaya M. Bilayer hydrogels for wound dressing and tissue engineering. Polymers, 2022, 14 (15): 3135. doi: 10.3390/polym14153135
    [11]
    Tang L, Xu Y, Liu F, et al. Synchronous ultraviolet polymerization strategy to improve the interfacial toughness of bilayer hydrogel actuators. Macromolecules, 2023, 56 (16): 6199–6207. doi: 10.1021/acs.macromol.3c00419
    [12]
    Chen Q, Zhang X Y, Chen K, et al. Bilayer hydrogels with low friction and high load-bearing capacity by mimicking the oriented hierarchical structure of cartilage. ACS Applied Materials & Interfaces, 2022, 14 (46): 52347–52358. doi: 10.1021/acsami.2c13641
    [13]
    Liu J Z, Miao J K, Zhao L, et al. Versatile bilayer hydrogel for wound dressing through PET-RAFT polymerization. Biomacromolecules, 2022, 23 (3): 1112–1123. doi: 10.1021/acs.biomac.1c01428
    [14]
    Peng W, Liu C, Lai Y J, et al. An adhesive/anti-adhesive Janus tissue patch for efficient closure of bleeding tissue with inhibited postoperative adhesion. Advanced Science, 2023, 10 (21): 2301427. doi: 10.1002/advs.202301427
    [15]
    Yao H, Wang C C, Zhang Y C, et al. Manufacture of bilayered composite hydrogels with strong, elastic, and tough properties for osteochondral repair applications. Biomimetics, 2023, 8 (2): 203. doi: 10.3390/biomimetics8020203
    [16]
    Li Y, Fu R Z, Duan Z G, et al. Mussel-inspired adhesive bilayer hydrogels for bacteria-infected wound healing via NIR-enhanced nanozyme therapy. Colloids and Surfaces B: Biointerfaces, 2022, 210: 112230. doi: 10.1016/j.colsurfb.2021.112230
    [17]
    Peers S, Montembault A, Ladavière C. Chitosan hydrogels for sustained drug delivery. Journal of Controlled Release, 2020, 326: 150–163. doi: 10.1016/j.jconrel.2020.06.012
    [18]
    Sapru S, Das S, Mandal M, et al. Sericin-chitosan-glycosamino glycans hydrogels incorporated with growth factors for in vitro and in vivo skin repair. Carbohydrate Polymers, 2021, 258: 117717. doi: 10.1016/j.carbpol.2021.117717
    [19]
    Liu F L, Wang L, Zhai X R, et al. A multi-functional double cross-linked chitosan hydrogel with tunable mechanical and antibacterial properties for skin wound dressing. Carbohydrate Polymers, 2023, 322: 121344. doi: 10.1016/j.carbpol.2023.121344
    [20]
    Nakan U, Bieerkehazhi S, Tolkyn B, et al. Synthesis, characterization and antibacterial application of copolymers based on N,N-dimethyl acrylamide and acrylic acid. Materials, 2021, 14 (20): 6191. doi: 10.3390/ma14206191
    [21]
    Bai C Z, Huang Q H, Zhang X, et al. Mechanical strengths of hydrogels of poly( N,N-dimethylacrylamide)/alginate with IPN and poly( N,N-dimethylacrylamide)/chitosan with semi-IPN microstructures. Macromolecular Materials and Engineering, 2019, 304 (11): 1900309. doi: 10.1002/mame.201900309
    [22]
    Bashir S, Hina M, Ramesh S, et al. Flexible and self-healable poly( N,N-dimethylacrylamide) hydrogels for supercapacitor prototype. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2021, 617: 126377. doi: 10.1016/j.colsurfa.2021.126377
    [23]
    Suresh D, Suresh A, Kannan R. Engineering biomolecular systems: Controlling the self-assembly of gelatin to form ultra-small bioactive nanomaterials. Bioactive Materials, 2022, 18: 321–336. doi: 10.1016/j.bioactmat.2022.02.035
    [24]
    Yan J, Li S Q, Chen G P, et al. Formation, physicochemical properties, and comparison of heat- and enzyme-induced whey protein-gelatin composite hydrogels. Food Hydrocolloids, 2023, 137: 108384. doi: 10.1016/j.foodhyd.2022.108384
    [25]
    Yuan X M, Zhu Z, Xia P C, et al. Tough gelatin hydrogel for tissue engineering. Advanced Science, 2023, 10 (24): 2301665. doi: 10.1002/advs.202301665
    [26]
    Pan Z, Fu Q Q, Wang M H, et al. Designing nanohesives for rapid, universal, and robust hydrogel adhesion. Nature Communications, 2023, 14 (1): 5378. doi: 10.1038/s41467-023-40753-5
    [27]
    Weber M, Steinle H, Golombek S, et al. Blood-contacting biomaterials: in vitro evaluation of the hemocompatibility. Frontiers in Bioengineering and Biotechnology, 2018, 6: 99. doi: 10.3389/fbioe.2018.00099
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