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Yara Örtüsü Uygulamaları için Antimikrobiyal Peptid Konjuge PEGDA Tabanlı Hidrojeller

Year 2025, Volume: 25 Issue: 6, 1511 - 1520

Abstract

Günümüzde, kronik yaraların bakımı önemli bir zorluk oluşturmaktadır. Kronik yaraların tedavisinde hidrojel bazlı yara örtüleri etkili bir yaklaşım olarak kabul edilmektedir. Poli(etilen glikol) diakrilat (PEGDA) hidrojeller, ayarlanabilir mekanik özellikler ve biyouyumluluk gibi özellikleri nedeniyle avantajlı bir hidrojel olarak kabul görmektedir. Ancak PEGDA hidrojelleri antimikrobiyal özelliklerden yoksundur. Bu nedenle, PEGDA hidrojellere antimikrobiyal özellikler kazanadırılması amacıyla yeni stratejilerin geliştirilmesi kronik enfekte yaralarla ilişkili sorunların üstesinden gelmek için kritik bir öneme sahiptir. Bu çalışmada, EDC/NHS kimyası kullanılarak antimikrobiyal peptit KSL-W'yi (KKVVFWVKFK) PEGDA hidrojeline konjuge ederek antimikrobiyal bir yara örtüsü geliştirilmiştir. Antimikrobiyal aktivite, planktonik formlarında MRSA ve çoklu ilaca dirençli (MDR) P. Aeruginosa üzerinde değerlendirilmiştir. Ayrıca, geliştirilen hidrojellerin sitotoksisitesi ve yara iyileşmesi üzerindeki etkinliği L929 fare fibroblast hücreleri kullanılarak değerlendirilmiştir. Geliştirilen KSL-W peptit konjuge PEGDA hidrojelleri, MRSA ve MDR P. aeruginosa'ya karşı sırasıyla 2,44 ve 1,15 log'luk inhibisyon ile güçlü antimikrobiyal aktivite göstermiştir. Ayrıca, geliştirilen hidrojeller sağlıklı memeli hücrelerine karşı istenmeyen toksik etki göstermemiş olup yara iyileşmesini desteklemiştir. Bulgularımız, biyomedikal uygulamalarda daha etkili fonksiyonel yara örtüleri geliştirmesi amacıyla antimikrobiyal hidrojellerin tasarımı açısından yol gösterici niteliktedir.

References

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  • Browe, D. P., Wood, C., Sze, M. T., White, K. A., Scott, T., Olabisi, R. M. and Freeman, J. W. (2017). "Characterization and optimization of actuating poly(ethylene glycol) diacrylate/acrylic acid hydrogels as artificial muscles." Polymer 117: 331-341. https://doi.org/10.1016/j.polymer.2017.04.044.
  • Camó, C., Bonaterra, A., Badosa, E., Baró, A., Montesinos, L., Montesinos, E., Planas, M. and Feliu, L. (2019). "Antimicrobial peptide KSL-W and analogues: Promising agents to control plant diseases." Peptides 112: 85-95. https://doi.org/10.1016/j.peptides.2018.11.009.
  • Castaño, A. G. (2017). Engineering poly (ethylene glycol) diacrylate-based microstructures to develop an in vitro model of small intestinal epithelium. PhD, Universitat de Barcelona.
  • Clevenger, A. J., Jimenez-Vergara, A. C., Tsai, E. H., de Barros Righes, G., Díaz-Lasprilla, A. M., Ramírez-Caballero, G. E. and Munoz-Pinto, D. J. (2022). "Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts." Gels 9(1). https://doi.org/10.3390/gels9010028.
  • Firlar, I., Altunbek, M., McCarthy, C., Ramalingam, M. and Camci-Unal, G. (2022). "Functional Hydrogels for Treatment of Chronic Wounds." Gels 8(2). https://doi.org/10.3390/gels8020127.
  • Gao, Y., Zhang, W., Cheng, Y. F., Cao, Y., Xu, Z., Xu, L. Q., Kang, Y. and Xue, P. (2021). "Intradermal administration of green synthesized nanosilver (NS) through film-coated PEGDA microneedles for potential antibacterial applications." Biomaterials Science 9(6): 2244-2254. https://doi.org/10.1039/D0BM02136A.
  • Gera, S., Kankuri, E. and Kogermann, K. (2022). "Antimicrobial peptides – Unleashing their therapeutic potential using nanotechnology." Pharmacol. Ther. 232: 107990. https://doi.org/10.1016/j.pharmthera.2021.107990
  • Huang, L., Zhu, Z., Wu, D., Gan, W., Zhu, S., Li, W., Tian, J., Li, L., Zhou, C. and Lu, L. (2019). "Antibacterial poly (ethylene glycol) diacrylate/chitosan hydrogels enhance mechanical adhesiveness and promote skin regeneration." Carbohydrate Polymers 225: 115110. https://doi.org/10.1016/j.carbpol.2019.115110.
  • Imani, M., Sharifi, S. and Ziaee, F. (2007). "Monitoring of Polyethylene Glycol-diacrylate-based Hydrogel Formation by Real Time NMR Spectroscopy." Iran. Polym. J. 16: 13-20.
  • Lei, J., Sun, L., Huang, S., Zhu, C., Li, P., He, J., Mackey, V., Coy, D. H. and He, Q. (2019). "The antimicrobial peptides and their potential clinical applications." Am J Transl Res 11(7): 3919-3931.
  • Lensen, M. C., Schulte, V. A. and Diez, M. (2011). "Cell Adhesion and spreading on an intrinsically anti-adhesive PEG biomaterial." Biomaterials—Physics and Chemistry: 397-414.
  • Levin, M., Tang, Y., Eisenbach, C. D., Valentine, M. T. and Cohen, N. (2024). Understanding the Response of Poly(ethylene glycol) diacrylate (PEGDA) Hydrogel Networks: A Statistical Mechanics-Based Framework. Macromolecules 57(15): 7074-7086. https://doi.org/10.1021/acs.macromol.3c02635.
  • Liang, Y., He, J. and Guo, B. (2021). "Functional Hydrogels as Wound Dressing to Enhance Wound Healing." ACS Nano 15(8): 12687-12722. https://doi.org/10.1021/acsnano.1c04206.
  • Lowe, A. B., Hoyle, C. E. and Bowman, C. N. (2010). "Thiol-yne click chemistry: A powerful and versatile methodology for materials synthesis." Journal of Materials Chemistry 20(23): 4745-4750. https://doi.org/10.1039/B917102A.
  • Lyu, Y. and Azevedo, H. S. (2021). "Supramolecular Hydrogels for Protein Delivery in Tissue Engineering." Molecules 26(4). https://doi.org/10.3390/molecules26040873.
  • Maria Teresa, N.-P., Steffen, P. and Gnana Prakash, G. (2012). UV Light Effects on Proteins: From Photochemistry to Nanomedicine. Molecular Photochemistry. S. Satyen. Rijeka, IntechOpen: Ch. 7.
  • Myat, Y. Y., Ngawhirunpat, T., Rojanarata, T., Opanasopit, P., Bradley, M., Patrojanasophon, P. and Pornpitchanarong, C. (2022) "Synthesis of Polyethylene Glycol Diacrylate/Acrylic Acid Nanoparticles as Nanocarriers for the Controlled Delivery of Doxorubicin to Colorectal Cancer Cells." Pharmaceutics 14 https://doi.org/10.3390/pharmaceutics14030479.
  • Nguyen, D.-V., Yuan, Y., Kukumberg, M., Wang, L., Lim, S. H., Hassanbhai, A. M., Chong, M., Kofidis, T., Tan, E. C. K., Seliktar, D., Kang, L. and Rufaihah, A. J. (2024). "Controlled release of vancomycin from PEGylated fibrinogen polyethylene glycol diacrylate hydrogel." Biomaterials Advances 161: 213896. https://doi.org/10.1016/j.bioadv.2024.213896.
  • Nurlidar, F., Rahayu, D. P., Lasmawati, D., Yunus, A. L., Heryani, R. and Suryani, N. (2023). "A simple method for the simultaneous encapsulation of ciprofloxacin into PEGDA/alginate hydrogels using gamma irradiation." Arab. J. Chem. 16(7): 104793. https://doi.org/10.1016/j.arabjc.2023.104793.
  • Onak, G., Ercan, U. K. and Karaman, O. (2020). "Antibacterial activity of antimicrobial peptide-conjugated nanofibrous membranes." Biomed Mater 16(1): 015020. https://doi.org/10.1088/1748-605X/abb722.
  • Prabhakar, T., Giaretta, J., Zulli, R., Rath, R. J., Farajikhah, S., Talebian, S. and Dehghani, F. (2025). "Covalent immobilization: A review from an enzyme perspective." Chemical Engineering Journal 503: 158054. https://doi.org/10.1016/j.cej.2024.158054.
  • Prakash Parthiban, S., Rana, D., Jabbari, E., Benkirane-Jessel, N. and Ramalingam, M. (2017). "Covalently immobilized VEGF-mimicking peptide with gelatin methacrylate enhances microvascularization of endothelial cells." Acta Biomaterialia 51: 330-340. https://doi.org/10.1016/j.actbio.2017.01.046.
  • Sen, C. K., Gordillo, G. M., Roy, S., Kirsner, R., Lambert, L., Hunt, T. K., Gottrup, F., Gurtner, G. C. and Longaker, M. T. (2009). "Human skin wounds: a major and snowballing threat to public health and the economy." Wound Repair Regen 17(6): 763-771. https://doi.org/10.1111/j.1524-475X.2009.00543.x.
  • Theberge, S., Semlali, A., Alamri, A., Leung, K. P. and Rouabhia, M. J. B. m. (2013). "C. albicans growth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W." BMC Microbiol. 13: 1-14. https://doi.org/10.1186/1471-2180-13-246.
  • Zhu, J., Tang, C., Kottke-Marchant, K. and Marchant, R. E. (2009). "Design and synthesis of biomimetic hydrogel scaffolds with controlled organization of cyclic RGD peptides." Bioconjug Chem 20(2): 333-339. https://doi.org/10.1021/bc800441v.

Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications

Year 2025, Volume: 25 Issue: 6, 1511 - 1520

Abstract

Currently, management of chronic wounds pose a significant challenge. In the treatment of chronic wounds, hydrogel based wound dressings considered as an effective approach. Poly(ethylene glycol) diacrylate (PEGDA) hydrogel is an advantageous hydrogel due to its properties such as tunable mechanical properties and biocompatibility. However, PEGDA hydrogels lack antimicrobial properties. Therefore, the development of new antibacterial strategies combined with PEGDA hydrogel can be effective in overcoming the problems associated with chronic infected wounds. Herein, we developed an antimicrobial wound dressing by conjugating antimicrobial peptide KSL-W (KKVVFWVKFK) to PEGDA hydrogel via EDC/NHS chemistry. The antimicrobial activity was evaluated against MRSA and multi-drug resistant (MDR) P. aeruginosa in their planktonic form. Furthermore, cytotoxicity and wound healing were assessed using L929 mouse fibroblast cells. Developed KSL-W peptide conjugated PEGDA hydrogels showed strong antimicrobial activity against MRSA and MDR P. aeruginosa with a bacterial reduction of 2.44 and 1.15 log, respectively. Furthermore, developed hydrogels showed no undesired toxic effect against healthy mammalian cells and supported wound healing. Our findings provide insight into the development of antimicrobial hydrogels for biomedical applications to develop more effective antimicrobial wound dressing solutions.

References

  • Barreto-Santamaría, A., Arévalo-Pinzón, G., Patarroyo, M. A. and Patarroyo, M. E. (2021) "How to Combat Gram-Negative Bacteria Using Antimicrobial Peptides: A Challenge or an Unattainable Goal?" Antibiotics 10 https://doi.org/10.3390/antibiotics10121499
  • Browe, D. P., Wood, C., Sze, M. T., White, K. A., Scott, T., Olabisi, R. M. and Freeman, J. W. (2017). "Characterization and optimization of actuating poly(ethylene glycol) diacrylate/acrylic acid hydrogels as artificial muscles." Polymer 117: 331-341. https://doi.org/10.1016/j.polymer.2017.04.044.
  • Camó, C., Bonaterra, A., Badosa, E., Baró, A., Montesinos, L., Montesinos, E., Planas, M. and Feliu, L. (2019). "Antimicrobial peptide KSL-W and analogues: Promising agents to control plant diseases." Peptides 112: 85-95. https://doi.org/10.1016/j.peptides.2018.11.009.
  • Castaño, A. G. (2017). Engineering poly (ethylene glycol) diacrylate-based microstructures to develop an in vitro model of small intestinal epithelium. PhD, Universitat de Barcelona.
  • Clevenger, A. J., Jimenez-Vergara, A. C., Tsai, E. H., de Barros Righes, G., Díaz-Lasprilla, A. M., Ramírez-Caballero, G. E. and Munoz-Pinto, D. J. (2022). "Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts." Gels 9(1). https://doi.org/10.3390/gels9010028.
  • Firlar, I., Altunbek, M., McCarthy, C., Ramalingam, M. and Camci-Unal, G. (2022). "Functional Hydrogels for Treatment of Chronic Wounds." Gels 8(2). https://doi.org/10.3390/gels8020127.
  • Gao, Y., Zhang, W., Cheng, Y. F., Cao, Y., Xu, Z., Xu, L. Q., Kang, Y. and Xue, P. (2021). "Intradermal administration of green synthesized nanosilver (NS) through film-coated PEGDA microneedles for potential antibacterial applications." Biomaterials Science 9(6): 2244-2254. https://doi.org/10.1039/D0BM02136A.
  • Gera, S., Kankuri, E. and Kogermann, K. (2022). "Antimicrobial peptides – Unleashing their therapeutic potential using nanotechnology." Pharmacol. Ther. 232: 107990. https://doi.org/10.1016/j.pharmthera.2021.107990
  • Huang, L., Zhu, Z., Wu, D., Gan, W., Zhu, S., Li, W., Tian, J., Li, L., Zhou, C. and Lu, L. (2019). "Antibacterial poly (ethylene glycol) diacrylate/chitosan hydrogels enhance mechanical adhesiveness and promote skin regeneration." Carbohydrate Polymers 225: 115110. https://doi.org/10.1016/j.carbpol.2019.115110.
  • Imani, M., Sharifi, S. and Ziaee, F. (2007). "Monitoring of Polyethylene Glycol-diacrylate-based Hydrogel Formation by Real Time NMR Spectroscopy." Iran. Polym. J. 16: 13-20.
  • Lei, J., Sun, L., Huang, S., Zhu, C., Li, P., He, J., Mackey, V., Coy, D. H. and He, Q. (2019). "The antimicrobial peptides and their potential clinical applications." Am J Transl Res 11(7): 3919-3931.
  • Lensen, M. C., Schulte, V. A. and Diez, M. (2011). "Cell Adhesion and spreading on an intrinsically anti-adhesive PEG biomaterial." Biomaterials—Physics and Chemistry: 397-414.
  • Levin, M., Tang, Y., Eisenbach, C. D., Valentine, M. T. and Cohen, N. (2024). Understanding the Response of Poly(ethylene glycol) diacrylate (PEGDA) Hydrogel Networks: A Statistical Mechanics-Based Framework. Macromolecules 57(15): 7074-7086. https://doi.org/10.1021/acs.macromol.3c02635.
  • Liang, Y., He, J. and Guo, B. (2021). "Functional Hydrogels as Wound Dressing to Enhance Wound Healing." ACS Nano 15(8): 12687-12722. https://doi.org/10.1021/acsnano.1c04206.
  • Lowe, A. B., Hoyle, C. E. and Bowman, C. N. (2010). "Thiol-yne click chemistry: A powerful and versatile methodology for materials synthesis." Journal of Materials Chemistry 20(23): 4745-4750. https://doi.org/10.1039/B917102A.
  • Lyu, Y. and Azevedo, H. S. (2021). "Supramolecular Hydrogels for Protein Delivery in Tissue Engineering." Molecules 26(4). https://doi.org/10.3390/molecules26040873.
  • Maria Teresa, N.-P., Steffen, P. and Gnana Prakash, G. (2012). UV Light Effects on Proteins: From Photochemistry to Nanomedicine. Molecular Photochemistry. S. Satyen. Rijeka, IntechOpen: Ch. 7.
  • Myat, Y. Y., Ngawhirunpat, T., Rojanarata, T., Opanasopit, P., Bradley, M., Patrojanasophon, P. and Pornpitchanarong, C. (2022) "Synthesis of Polyethylene Glycol Diacrylate/Acrylic Acid Nanoparticles as Nanocarriers for the Controlled Delivery of Doxorubicin to Colorectal Cancer Cells." Pharmaceutics 14 https://doi.org/10.3390/pharmaceutics14030479.
  • Nguyen, D.-V., Yuan, Y., Kukumberg, M., Wang, L., Lim, S. H., Hassanbhai, A. M., Chong, M., Kofidis, T., Tan, E. C. K., Seliktar, D., Kang, L. and Rufaihah, A. J. (2024). "Controlled release of vancomycin from PEGylated fibrinogen polyethylene glycol diacrylate hydrogel." Biomaterials Advances 161: 213896. https://doi.org/10.1016/j.bioadv.2024.213896.
  • Nurlidar, F., Rahayu, D. P., Lasmawati, D., Yunus, A. L., Heryani, R. and Suryani, N. (2023). "A simple method for the simultaneous encapsulation of ciprofloxacin into PEGDA/alginate hydrogels using gamma irradiation." Arab. J. Chem. 16(7): 104793. https://doi.org/10.1016/j.arabjc.2023.104793.
  • Onak, G., Ercan, U. K. and Karaman, O. (2020). "Antibacterial activity of antimicrobial peptide-conjugated nanofibrous membranes." Biomed Mater 16(1): 015020. https://doi.org/10.1088/1748-605X/abb722.
  • Prabhakar, T., Giaretta, J., Zulli, R., Rath, R. J., Farajikhah, S., Talebian, S. and Dehghani, F. (2025). "Covalent immobilization: A review from an enzyme perspective." Chemical Engineering Journal 503: 158054. https://doi.org/10.1016/j.cej.2024.158054.
  • Prakash Parthiban, S., Rana, D., Jabbari, E., Benkirane-Jessel, N. and Ramalingam, M. (2017). "Covalently immobilized VEGF-mimicking peptide with gelatin methacrylate enhances microvascularization of endothelial cells." Acta Biomaterialia 51: 330-340. https://doi.org/10.1016/j.actbio.2017.01.046.
  • Sen, C. K., Gordillo, G. M., Roy, S., Kirsner, R., Lambert, L., Hunt, T. K., Gottrup, F., Gurtner, G. C. and Longaker, M. T. (2009). "Human skin wounds: a major and snowballing threat to public health and the economy." Wound Repair Regen 17(6): 763-771. https://doi.org/10.1111/j.1524-475X.2009.00543.x.
  • Theberge, S., Semlali, A., Alamri, A., Leung, K. P. and Rouabhia, M. J. B. m. (2013). "C. albicans growth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W." BMC Microbiol. 13: 1-14. https://doi.org/10.1186/1471-2180-13-246.
  • Zhu, J., Tang, C., Kottke-Marchant, K. and Marchant, R. E. (2009). "Design and synthesis of biomimetic hydrogel scaffolds with controlled organization of cyclic RGD peptides." Bioconjug Chem 20(2): 333-339. https://doi.org/10.1021/bc800441v.
There are 26 citations in total.

Details

Primary Language English
Subjects Tissue Engineering, Biomaterial
Journal Section Articles
Authors

Buse Sezer 0009-0006-1656-8153

Eda Bilgiç 0009-0007-3525-0594

Günnur Pulat 0000-0003-0895-4768

Early Pub Date November 13, 2025
Publication Date November 15, 2025
Submission Date April 10, 2025
Acceptance Date June 14, 2025
Published in Issue Year 2025 Volume: 25 Issue: 6

Cite

APA Sezer, B., Bilgiç, E., & Pulat, G. (2025). Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 25(6), 1511-1520.
AMA Sezer B, Bilgiç E, Pulat G. Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. November 2025;25(6):1511-1520.
Chicago Sezer, Buse, Eda Bilgiç, and Günnur Pulat. “Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 25, no. 6 (November 2025): 1511-20.
EndNote Sezer B, Bilgiç E, Pulat G (November 1, 2025) Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 25 6 1511–1520.
IEEE B. Sezer, E. Bilgiç, and G. Pulat, “Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 25, no. 6, pp. 1511–1520, 2025.
ISNAD Sezer, Buse et al. “Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 25/6 (November2025), 1511-1520.
JAMA Sezer B, Bilgiç E, Pulat G. Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2025;25:1511–1520.
MLA Sezer, Buse et al. “Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 25, no. 6, 2025, pp. 1511-20.
Vancouver Sezer B, Bilgiç E, Pulat G. Antimicrobial Peptide Conjugated PEGDA Based Hydrogel for Wound Dressing Applications. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2025;25(6):1511-20.