Mussel-Inspired Adhesive and Tough Hydrogel Based on Silk-Triggered Dopamine Polymerization for Wound Healing

Abstract

Tissue engineering is a great alternative to repair and regenerate damaged tissues and organs. Hydrogels are promising materials for tissue repair, but optimizing their various functions—such as adhesion, mechanical properties, and vascularization—to suit the complexity of different organs and tissues remains a significant challenge. In this study, we explore a tough and adhesive polydopamine (PDA)-silk-polyacrylamide (PAM) hydrogel inspired by the mussel-inspired adhesion of PDA and the vascularization potential of silk. Through a Schiff base reaction, self-polymerization occurs between the free dopamine and the conjugated dopamine on the silk chains, resulting in the formation of a PDA/silk prepolymer. The presence of PDA in the prepolymer endows the resulting PDA-silk-PAM hydrogel with excellent adhesiveness, strong mechanical properties, and good water absorption. By adjusting the degree of crosslinking, the hydrogel also demonstrates impressive deformability, making it suitable for engineering thicker and more complex tissues and organs. Moreover, benefiting from the vascularization capabilities of silk and the adhesive properties of PDA, the PDA-silk-PAM hydrogel effectively promotes vascularization and accelerates wound healing in full-thickness skin wounds on the backs of Sprague-Dawley rats. Overall, our study provides a straightforward approach to create versatile medical hydrogel with strong potential for clinical applications.

Keywords

adhesive hydrogel / polydopamine / Schiff base reaction / silk / wound healing

References

[1] H. Zhang, J. Guo, Y. Wang, L. Shang, R. Chai, and Y. Zhao, “Natural Polymer-Derived Bioscaffolds for Peripheral Nerve Regeneration,” Advanced Functional Materials 32 (2022): 2203829.

[2] C. Liu, K. Peng, Y. Wu, and F. Fu, “Functional Adhesive Hydrogels for Biological Interfaces,” Smart Medicine 2 (2023): e20230024.

[3] H. Zhang, L. Sun, J. Guo, and Y. Zhao, “Hierarchical Spinning of Janus Textiles With Anisotropic Wettability for Wound Healing,” Research 6 (2023): 0129.

[4] C. Mao, Y. Xiang, X. Liu, et al., “Photo-Inspired Antibacterial Activity and Wound Healing Acceleration by Hydrogel Embedded With Ag/Ag@AgCl/ZnO Nanostructures,” ACS Nano 11 (2017): 9010–9021.

[5] S. Yu, G. Li, P. Zhao, et al., “NIR-Laser-Controlled Hydrogen-Releasing PdH Nanohydride for Synergistic Hydrogen-Photothermal Antibacterial and Wound-Healing Therapies,” Advanced Functional Materials 29 (2019): 1905697.

[6] J. Zhang, Y. Zheng, J. Lee, et al., “A Pulsatile Release Platform Based on Photo-Induced Imine-Crosslinking Hydrogel Promotes Scarless Wound Healing,” Nature Communications 12 (2021): 1670.

[7] Y. Zhao, Z. Li, S. Song, et al., “Skin-Inspired Antibacterial Conductive Hydrogels for Epidermal Sensors and Diabetic Foot Wound Dressings,” Advanced Functional Materials 29 (2019): 1901474.

[8] T. Jiang, T. Wang, T. Li, et al., “Enhanced Transdermal Drug Delivery by Transfersome-Embedded Oligopeptide Hydrogel for Topical Chemotherapy of Melanoma,” ACS Nano 12 (2018): 9693–9701.

[9] Z. Yang, R. Huang, B. Zheng, et al., “Highly Stretchable, Adhesive, Biocompatible, and Antibacterial Hydrogel Dressings for Wound Healing,” Advanced Science 8 (2021): 2003627.

[10] H. Zhang, X. Sun, J. Wang, et al., “Multifunctional Injectable Hydrogel Dressings for Effectively Accelerating Wound Healing: Enhancing Biomineralization Strategy,” Advanced Functional Materials 31 (2021): 2100093.

[11] M. Farokhi, M. Aleemardani, A. Solouk, H. Mirzadeh, A. H. Teuschl, and H. Redl, “Crosslinking Strategies for Silk Fibroin Hydrogels: Promising Biomedical Materials,” Biomedical Materials 16 (2021): 022004.

[12] W. Li, X. Yang, P. Lai, and L. Shang, “Bio-Inspired Adhesive Hydrogel for Biomedicine-Principles and Design Strategies,” Smart Medicine 1 (2022): e20220024.

[13] J. Luo, J. Yang, X. Zheng, et al., “A Highly Stretchable, Real-Time Self-Healable Hydrogel Adhesive Matrix for Tissue Patches and Flexible Electronics,” Advanced Healthcare Materials 9 (2020): 1901423.

[14] L. Han, X. Lu, K. Liu, et al., “Mussel-Inspired Adhesive and Tough Hydrogel Based on Nanoclay Confined Dopamine Polymerization,” ACS Nano 11 (2017): 2561–2574.

[15] T. Su, M. Zhang, Q. Zeng, et al., “Mussel-Inspired Agarose Hydrogel Scaffolds for Skin Tissue Engineering,” Bioactive Materials 6 (2021): 579–588.

[16] Z. Tang, F. Jiang, Y. Zhang, et al., “Mussel-Inspired Injectable Hydrogel and Its Counterpart for Actuating Proliferation and Neuronal Differentiation of Retinal Progenitor Cells,” Biomaterials 194 (2019): 57–72.

[17] Q. Yang, L. Tang, C. Guo, et al., “A Bioinspired Gallol-Functionalized Collagen as Wet-Tissue Adhesive for Biomedical Applications,” Chemical Engineering Journal 417 (2021): 127962.

[18] F. Jiang, Z. Chi, Y. Ding, et al., “Wound Dressing Hydrogel of Enteromorpha prolifera Polysaccharide-Polyacrylamide Composite: A Facile Transformation of Marine Blooming into Biomedical Material,” ACS Applied Materials & Interfaces 13 (2021): 14530–14542.

[19] H. Lee, S. M. Dellatore, W. M. Miller, and P. B. Messersmith, “Mussel-Inspired Surface Chemistry for Multifunctional Coatings,” Science 318 (2007): 426–430.

[20] Z. Rao, S. Liu, R. Wu, et al., “Fabrication of Dual Network Self-Healing Alginate/Guar Gum Hydrogels Based on Polydopamine-Type Microcapsules From Mesoporous Silica Nanoparticles,” International Journal of Biological Macromolecules 129 (2019): 916–926.

[21] P. J. M. Bouten, M. Zonjee, J. Bender, et al., “The Chemistry of Tissue Adhesive Materials,” Progress in Polymer Science 39 (2014): 1375–1405.

[22] W. Dou, X. Zeng, S. Zhu, Y. Zhu, H. Liu, and S. Li, “Mussel-Inspired Injectable Adhesive Hydrogels for Biomedical Applications,” International Journal of Molecular Sciences 25 (2024): 9100.

[23] X. Gao, Q. Dai, L. Yao, H. Dong, Q. Li, and X. Cao, “A Medical Adhesive Used in a Wet Environment by Blending Tannic Acid and Silk Fibroin,” Biomaterials Science 8 (2020): 2694–2701.

[24] E. R. Johnston, Y. Miyagi, J. A. Chuah, K. Numata, and M. A. Serban, “The Interplay Between Silk Fibroin's Structure and Its Adhesive Properties,” ACS Biomaterials Science & Engineering 4 (2018): 2815–2824.

[25] H. Zhang, D. Xu, Y. Zhang, M. Li, and R. Chai, “Silk Fibroin Hydrogels for Biomedical Applications,” Smart Medicine 1 (2022): e20220011.

[26] H. Han, H. Ning, S. Liu, et al., “Silk Biomaterials With Vascularization Capacity,” Advanced Functional Materials 26 (2016): 421–436.

[27] S. Chen, S. Liu, L. Zhang, et al., “Construction of Injectable Silk Fibroin/Polydopamine Hydrogel for Treatment of Spinal Cord Injury,” Chemical Engineering Journal 399 (2020): 125795.

[28] F. Fu, C. Liu, Z. Jiang, et al., “Polymeric Silk Fibroin Hydrogel as a Conductive and Multifunctional Adhesive for Durable Skin and Epidermal Electronics,” Smart Medicine 3 (2024): e20240027.

[29] S. Bai, X. Zhang, P. Cai, et al., “A Silk-Based Sealant With Tough Adhesion for Instant Hemostasis of Bleeding Tissues,” Nanoscale Horizons 4 (2019): 1333–1341.

[30] C. Ma, J. Sun, B. Li, et al., “Ultra-Strong Bio-Glue From Genetically Engineered Polypeptides,” Nature Communications 12 (2021): 3613.

[31] J. W. Seo, H. Kim, K. Kim, S. Q. Choi, and H. J. Lee, “Calcium-Modified Silk as a Biocompatible and Strong Adhesive for Epidermal Electronics,” Advanced Functional Materials 28 (2018): 1800802.

[32] T. Xu, R. Yang, X. Ma, et al., “Bionic Poly(γ-Glutamic Acid) Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars,” Advanced Healthcare Materials 8 (2019): 1900123.

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2025 The Author(s). Smart Medicine published by Wiley-VCH GmbH on behalf of Wenzhou Institute, University of Chinese Academy of Sciences.