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Facile synthesis of self-healing gels via frontal polymerization toward acid–base regulatable wound dressing

  • Materials for life sciences
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Abstract

Advanced pH-regulated wound dressing that can promote wound healing remains a key challenge. To this end, we herein report a self-healing assembly strategy toward pH-regulated gel wound dressing. Firstly, we synthesized acrylic acid (AA)-based Gel 1 by a facile frontal polymerization (FP), which is rich in carboxy groups, endowing the gel with excellent self-healing and pH sensitivity. Then we constructed carboxymethyl chitosan and acrylamide (CMCS-AM)-based Gel 2, which shows reverse pH sensitivity against Gel 1. Thus, the Gel 1/Gel 2 bilayer exhibits different bending behaviors based on the reverse pH sensitivity, providing opportunities for pH regulation. More importantly, the in vivo study indicates that the Gel 1/Gel 2 assembly can effectively adjust the pH microenvironment, which consists of the non-infected wound pH change (from alkalinity to acidity and back again). The Gel 1 can continuously dissociate H+ to the wound, while the Gel 2 can adopt these ions, which synergistically realize the pH regulation based on the dissociation–adsorption rates difference and then accelerate the wound healing. This work offers a facile way to construct self-healing gels by FP, as well as a self-healing assembly strategy for advanced wound dressing with pH regulation, which is of great significance in wound healing area.

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References

  1. Liang YP, He JH, Guo BL (2021) Functional hydrogels as wound dressing to enhance wound healing. ACS Nano 15:12687. https://doi.org/10.1021/acsnano.1c04206

    Article  CAS  Google Scholar 

  2. Wathoni N, Motoyama K, Higashi T, Okajima M, Kaneko T, Arima H (2016) Physically crosslinked-sacran hydrogel films for wound dressing application. Int J Biol Macromol 89:465. https://doi.org/10.1016/j.ijbiomac.2016.05.006

    Article  CAS  Google Scholar 

  3. Chen T, Chen Y, Rehman HU, Chen Z, Yang Z, Wang M, Li H, Liu H (2018) Ultratough, self-healing, and tissue-adhesive hydrogel for wound dressing. ACS Appl Mater Interfaces 10:33523. https://doi.org/10.1021/acsami.8b10064

    Article  CAS  Google Scholar 

  4. Wallace LA, Gwynne L, Jenkins T (2019) Challenges and opportunities of pH in chronic wounds. Ther Deliv 10:719. https://doi.org/10.4155/tde-2019-0066

    Article  CAS  Google Scholar 

  5. Koehler J, Wallmeyer L, Hedtrich S, Goepferich AM, Brandl FP (2017) pH-Modulating poly(ethylene glycol)/Alginate hydrogel dressings for the treatment of chronic wounds. Macromol Biosci 17:1600369. https://doi.org/10.1002/mabi.201600369

    Article  CAS  Google Scholar 

  6. Wang S, Urban MW (2020) Self-healing polymers. Nat Rev Mater 5:562. https://doi.org/10.1038/s41578-020-0202-4

    Article  CAS  Google Scholar 

  7. Roels E, Terryn S, Iida F, Bosman AW, Norvez S, Clemens F, Van Assche G, Vanderborght B, Brancart J (2022) Processing of self-healing polymers for soft robotics. Adv Mater 34:2104798. https://doi.org/10.1002/adma.202104798

    Article  CAS  Google Scholar 

  8. Fernandez CA, Correa M, Nguyen M-T, Rod KA, Dai GL, Cosimbescu L, Rousseau R, Glezakou V-A (2021) Progress and challenges in self-healing cementitious materials. J Mater Sci 56:201. https://doi.org/10.1007/s10853-020-05164-7

    Article  CAS  Google Scholar 

  9. Wang W, Zeng Z, Xiang L, Liu C, Diaz-Dussan D, Du Z, Asha AB, Yang W, Peng Y-Y, Pan M, Narain R, Liu J, Zeng H (2021) Injectable self-healing hydrogel via biological environment-adaptive supramolecular assembly for gastric perforation healing. ACS Nano 15:9913. https://doi.org/10.1021/acsnano.1c01199

    Article  CAS  Google Scholar 

  10. Yang M, Wang L, Cheng Y, Ma K, Wei X, Jia P, Gong Y, Zhang Y, Yang J, Zhao J (2019) Light- and pH-responsive self-healing hydrogel. J Mater Sci 54:9983. https://doi.org/10.1007/s10853-019-03547-z

    Article  CAS  Google Scholar 

  11. Zhang Y, Wang Q, Wang Z, Zhang D, Gu J, Ye K, Su D, Zhang Y, Chen J, Barboiu M (2021) Strong, self-healing gelatin hydrogels cross-linked by double dynamic covalent chemistry. ChemPlusChem 86:1524. https://doi.org/10.1002/cplu.202100474

    Article  CAS  Google Scholar 

  12. Kuhl N, Bode S, Bose RK, Vitz J, Seifert A, Hoeppener S, Garcia SJ, Spange S, van der Zwaag S, Hager MD, Schubert US (2015) Acylhydrazones as reversible covalent crosslinkers for self-healing polymers. Adv Funct Mater 25:3295. https://doi.org/10.1002/adfm.201501117

    Article  CAS  Google Scholar 

  13. Hu X-H, Liu J-D, Du X-Y, Cheng R, Li Q, Chen S (2019) A facile synthesis of self-healing hydrogels toward flexible quantum dot-based luminescent solar concentrators and white LEDs. J Mater Chem C 7:10988. https://doi.org/10.1039/c9tc03215k

    Article  CAS  Google Scholar 

  14. Yang Y, Ding X, Urban MW (2015) Chemical and physical aspects of self-healing materials. Prog Polym Sci 49–50:34. https://doi.org/10.1016/j.progpolymsci.2015.06.001

    Article  CAS  Google Scholar 

  15. Li J, Geng L, Wang G, Chu H, Wei H (2017) Self-healable gels for use in wearable devices. Chem Mater 29:8932. https://doi.org/10.1021/acs.chemmater.7b02895

    Article  CAS  Google Scholar 

  16. Wang Y, Shang L, Chen G, Sun L, Zhang X, Zhao Y (2020) Bioinspired structural color patch with anisotropic surface adhesion. Sci Adv 6:eaax8258. https://doi.org/10.1126/sciadv.aax8258

    Article  CAS  Google Scholar 

  17. Fu F, Chen Z, Zhao Z, Wang H, Shang L, Gu Z, Zhao Y (2017) Bio-inspired self-healing structural color hydrogel. PNAS 114:5900–5905. https://doi.org/10.1073/pnas.1703616114

    Article  CAS  Google Scholar 

  18. Harada A, Kobayashi R, Takashima Y, Hashidzume A, Yamaguchi H (2011) Macroscopic self-assembly through molecular recognition. Nat Chem 3:34. https://doi.org/10.1038/nchem.893

    Article  CAS  Google Scholar 

  19. Harada A, Takashima Y, Hashidzume A, Yamaguchi H (2021) Supramolecular polymers and materials formed by host-guest interactions. Bull Chem Soc Jpn 94:2381. https://doi.org/10.1246/bcsj.20210233

    Article  CAS  Google Scholar 

  20. Liu J-D, Du X-Y, Hao L-W, Li Q, Chen S (2020) Macroscopic self-assembly of gel-based microfibers toward functional nonwoven fabrics. ACS Appl Mater Interfaces 12:50823. https://doi.org/10.1021/acsami.0c14421

    Article  CAS  Google Scholar 

  21. Li Q, Zhang Y-W, Wang C-F, Weitz DA, Chen S (2018) Versatile hydrogel ensembles with macroscopic multidimensions. Adv Mater 30:1803475. https://doi.org/10.1002/adma.201803475

    Article  CAS  Google Scholar 

  22. Li Q, Liu J-D, Liu S-S, Wang C-F, Chen S (2019) Frontal polymerization-oriented self-healing hydrogels and applications toward temperature-triggered actuators. Ind Eng Chem Res 58:3885. https://doi.org/10.1021/acs.iecr.8b05369

    Article  CAS  Google Scholar 

  23. He Y-Y, Liu J-D, Cheng R, Liu C, Ye H-G, Hao L-W, Li Q, Chen S (2021) Microfluidic-assisted assembly of fluorescent self-healing gel particles toward dual-signal sensors. J Mater Sci 56:14832. https://doi.org/10.1007/s10853-021-05992-1

    Article  CAS  Google Scholar 

  24. Li Q, Xu Z, Du X, Du X-Y, Cheng H, Wu G, Wang C-F, Cui Z, Chen S (2018) Microfluidic-directed hydrogel fabrics based on interfibrillar self-healing effect. Chem Mater 30:8822–8828. https://doi.org/10.1021/acs.chemmater.8b03579

    Article  CAS  Google Scholar 

  25. Davtyan SP, Berlin AA, Tonoyan AO (2011) Advances and problems of frontal polymerization processes. Rev J Chem 1:56–92. https://doi.org/10.1134/S207997801101002X

    Article  Google Scholar 

  26. Li Q, Shen H-X, Liu C, Wang C-F, Zhu L, Chen S (2022) Advances in frontal polymerization strategy: from fundamentals to applications. Prog Polym Sci 127:101514. https://doi.org/10.1016/j.progpolymsci.2022.101514

    Article  CAS  Google Scholar 

  27. Zhou Z-F, Yu C, Wang X-Q, Tang W-Q, Wang C-F, Chen S (2013) Facile access to poly(NMA-co-VCL) hydrogels via long range laser ignited frontal polymerization. J Mater Chem A 1:7326. https://doi.org/10.1039/C3TA11409K

    Article  CAS  Google Scholar 

  28. Yu C, Wang C-F, Chen S (2014) Robust self-healing host-guest gels from magnetocaloric radical polymerization. Adv Funct Mater 24:1235. https://doi.org/10.1002/adfm.201302058

    Article  CAS  Google Scholar 

  29. Shen H, Wang H-P, Wang C-F, Zhu L, Li Q, Chen S (2021) Rapid fabrication of patterned gels via microchannel-conformal frontal polymerization. Macromol Rapid Commun 42:2100421. https://doi.org/10.1002/marc.202100421

    Article  CAS  Google Scholar 

  30. Robertson ID, Hernandez HL, White SR, Moore JS (2014) Rapid stiffening of a microfluidic endoskeleton via frontal polymerization. ACS Appl Mater Interfaces 6:18469. https://doi.org/10.1021/am5061596

    Article  CAS  Google Scholar 

  31. Robertson ID, Yourdkhani M, Centellas PJ, Aw JE, Ivanoff DG, Goli E, Lloyd EM, Dean LM, Sottos NR, Geubelle PH, Moore JS, White SR (2018) Rapid energy-efficient manufacturing of polymers and composites via frontal polymerization. Nature 557:223. https://doi.org/10.1038/s41586-018-0054-x

    Article  CAS  Google Scholar 

  32. Sanna R, Sanna D, Alzari V, Nuvoli D, Scognamillo S, Piccinini M, Lazzari M, Gioffredi E, Malucelli G, Mariani A (2012) Synthesis and characterization of graphene-containing thermoresponsive nanocomposite hydrogels of poly(N-vinylcaprolactam) prepared by frontal polymerization. J Polym Sci Part A: Polym Chem 50:4110. https://doi.org/10.1002/pola.26215

    Article  CAS  Google Scholar 

  33. Scognamillo S, Bounds C, Luger M, Mariani A, Pojman JA (2010) Frontal cationic curing of epoxy resins. J Polym Sci Part A: Polym Chem 48:2000–2005. https://doi.org/10.1002/pola.23967

    Article  CAS  Google Scholar 

  34. Nuvoli D, Alzari V, Pojman JA, Sanna V, Ruiu A, Sanna D, Malucelli G, Mariani A (2015) Synthesis and characterization of functionally gradient materials obtained by frontal polymerization. ACS Appl Mater Interfaces 7:3600. https://doi.org/10.1021/am507725k

    Article  CAS  Google Scholar 

  35. Rassu M, Alzari V, Nuvoli D, Nuvoli L, Sanna D, Sanna V, Malucelli G, Mariani A (2017) Semi-interpenetrating polymer networks of methyl cellulose and polyacrylamide prepared by frontal polymerization. J Polym Sci Part A: Polym Chem 55:1268. https://doi.org/10.1002/pola.28498

    Article  CAS  Google Scholar 

  36. Feng Q, Yan QZ, Ge CC (2013) Frontal polymerization synthesis and characterization of temperature- and pH-sensitive hydrogels. Colloid Polym Sci 291:1163. https://doi.org/10.1007/s00396-012-2844-2

    Article  CAS  Google Scholar 

  37. Liu Y, Cheng Y, Zhao C, Wang H, Zhao Y (2022) Nanomotor-derived porous biomedical particles from droplet microfluidics. Adv Sci 9:2104272. https://doi.org/10.1002/advs.202104272

    Article  CAS  Google Scholar 

  38. Zhao Y, Su H, Fang L, Tan T (2005) Superabsorbent hydrogels from poly(aspartic acid) with salt-, temperature- and pH-responsiveness properties. Polymer 46:5368. https://doi.org/10.1016/j.polymer.2005.04.015

    Article  CAS  Google Scholar 

  39. Shao H, Wang C-F, Chen S, Xu C (2014) Fast fabrication of superabsorbent polyampholytic nanocomposite hydrogels via plasma-ignited frontal polymerization. J Polym Sci PART A: Polym Chem 52:912. https://doi.org/10.1002/pola.27086

    Article  CAS  Google Scholar 

  40. Yu C, Wang C-F, Chen S (2015) Facile access to versatile hydrogels via interface-directed frontal polymerization derived from the magnetocaloric effect. J Mater Chem A 3:17351. https://doi.org/10.1039/C5TA03811A

    Article  CAS  Google Scholar 

  41. Wang C, Liu J-D, Li Q, Chen S (2019) Self-healing hydrogel toward metal ion rapid removal via available solar-driven fashion. Ind Eng Chem Res 58:17067. https://doi.org/10.1021/acs.iecr.9b03250

    Article  CAS  Google Scholar 

  42. Perova TS, Vij JK, Xu H (1997) Fourier transform infrared study of poly (2-hydroxyethyl methacrylate) PHEMA. Colloid Polym Sci 275:323. https://doi.org/10.1007/s003960050089

    Article  CAS  Google Scholar 

  43. Cui T, Yu J, Wang C-F, Chen S, Li Q, Guo K, Qing R, Ge W, Ren J (2022) Micro-gel ensembles for accelerated healing of chronic wound via pH regulation. Adv Sci. https://doi.org/10.1002/advs.202201254

    Article  Google Scholar 

  44. Ata S, Rasool A, Islam A, Bibi I, Rizwan M, Azeem MK, Qureshi AR, Iqbal M (2020) Loading of Cefixime to pH sensitive chitosan based hydrogel and investigation of controlled release kinetics. Int J Biol Macromol 155:1236. https://doi.org/10.1016/j.ijbiomac.2019.11.091

    Article  CAS  Google Scholar 

  45. Omera AM, Sadik WA-A, El-Demerdash A-GM, Hassan HS (2021) Formulation of pH-sensitive aminated chitosan–gelatin crosslinked hydrogel for oral drug delivery. J Saudi Chem Soc 25:101384. https://doi.org/10.1016/j.jscs.2021.101384

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by National Natural Science Foundation of China (21908103, 21736006, 81870396 and 21978132), Natural Science Foundation of Jiangsu Province (BK20190672, BK20211133) and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Jiangsu Key Laboratory of Fine Chemicals and Functional Polymer Materials, Nanjing Tech University, No. 5 Xin Mofan Road, Nanjing, 210009, People’s Republic of China

    Zi-Liang He, Ji-Dong Liu, Cai-Feng Wang, Qing Li & Su Chen

  2. Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China

    Jie Hu & Gefei Wang

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  1. Zi-Liang He
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  2. Ji-Dong Liu
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  3. Jie Hu
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  4. Cai-Feng Wang
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  5. Qing Li
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  7. Su Chen
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Contributions

ZH contributed to investigation, methodology, validation, software, data curation, formal analysis, visualization and writing—original draft. JL performed investigation, methodology, data curation, validation and writing—original draft. JH performed investigation, methodology, data curation and validation. CFW contributed to data curation, formal analysis, writing—review and editing, and funding acquisition. QL contributed to conceptualization, formal analysis, resources, visualization, project administration, writing—review and editing, and funding acquisition. GW performed writing—review and editing, and funding acquisition. SC contributed to conceptualization, formal analysis, project administration, supervision, writing—review and editing, and funding acquisition.

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Correspondence to Qing Li or Su Chen.

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He, ZL., Liu, JD., Hu, J. et al. Facile synthesis of self-healing gels via frontal polymerization toward acid–base regulatable wound dressing. J Mater Sci 57, 12971–12984 (2022). https://doi.org/10.1007/s10853-022-07403-5

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