journal article·2026-02-08Open access

Which Strategies Can Be Effective Against Chronic Infected Wounds?

Magdalena Ratajczak, Dorota Kaminska, Wiktoria Nowicka, Jolanta Dlugaszewska, Marzena Gajecka

Applied Sciences· Volume 16· Issue 4

Abstract

Chronic wounds pose a significant therapeutic challenge due to their complex etiology, long patient treatment time and high treatment costs. Wound healing is hindered by the presence of necrotic tissue, elevated pH, and biofilm formation. The key therapeutic approach involves regular wound debridement combined with appropriate antimicrobial agents. Due to increasing bacterial resistance and biofilm forming, there is an urgent need for effective therapies that eliminate biofilm and support the healing process. Here we discuss innovative approaches for treating infected chronic wounds, including the use of hydrogels, photodynamic therapy, probiotics, and phage therapy. Advances in these methods, such as chemical modifications and nanotechnology applications, open up new possibilities for effective wound treatment. The greatest potential for clinical application lies in strategies based on advanced hydrogels and antibacterial dressings, as well as photodynamic therapy.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Wound Healing and Treatments · Bacterial biofilms and quorum sensing · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Poznan University of Medical Sciences, Chair and Department of Genetics and Pharmaceutical Microbiology, Rokietnicka 3, 60-806 Poznan, Poland

Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland

References (100+)

Show source-provided references
1. Chronic Wounds: Evaluation and Management
2. Diagnosis and treatment of infected wounds: A multi-centre audit of current clinical practice across the UK, Ireland and Scandinavia10.1111/jocn.16527 ↗
3. The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice10.1016/j.heliyon.2023.e18246 ↗
4. Diban, F., Di Lodovico, S., Di Fermo, P., D’Ercole, S., D’Arcangelo, S., Di Giulio, M., and Cellini, L. (2023). Biofilms in Chronic Wound Infections: Innovative Antimicrobial Approaches Using the In Vitro Lubbock Chronic Wound Biofilm Model. Int. J. Mol. Sci., 24.10.3390/ijms24021004 ↗
5. Burn wound infections microbiome and novel approaches using therapeutic microorganisms in burn wound infection control10.1016/j.addr.2023.114769 ↗
6. Durand, B.A.R.N., Pouget, C., Magnan, C., Molle, V., Lavigne, J.P., and Dunyach-Remy, C. (2022). Bacterial Interactions in the Context of Chronic Wound Biofilm: A Review. Microorganisms, 10.10.3390/microorganisms10081500 ↗
7. Microbial predictors of healing and short-term effect of debridement on the microbiome of chronic wounds10.1038/s41522-020-0130-5 ↗
8. A biofilm based wound care pathway in the community setting: A review
9. Diagnostics for Wound Infections10.1089/wound.2019.1103 ↗
10. Biofilm Management in Wound Care10.1097/PRS.0000000000008142 ↗
11. Human Wound and Its Burden: Updated 2020 Compendium of Estimates10.1089/wound.2021.0026 ↗
12. Negative Pressure Level and Effects on Bacterial Growth Kinetics in an in vitro Wound Model10.33073/pjm-2024-018 ↗
13. Ratajczak, M., Kaminska, D., Matuszewska, E., Hołderna-Kedzia, E., Rogacki, J., and Matysiak, J. (2021). Promising Antimicrobial Properties of Bioactive Compounds from Different Honeybee Products. Molecules, 26.10.3390/molecules26134007 ↗
14. Antimicrobial stewardship in wound care: A Position Paper from the British Society for Antimicrobial Chemotherapy and European Wound Management Association10.1093/jac/dkw287 ↗
15. Hydrogel wound dressings for bioactive treatment of acute and chronic wounds10.1016/j.eurpolymj.2017.12.046 ↗
16. Alven, S., and Aderibigbe, B.A. (2020). Chitosan and Cellulose-Based Hydrogels for Wound Management. IJMS, 21.10.3390/ijms21249656 ↗
17. Living Bacterial Hydrogels for Accelerated Infected Wound Healing10.1002/advs.202102545 ↗
18. Abed, S., Beig, M., Barzi, S.M., Shafiei, M., Hashemi Shahraki, A., Sadeghi, S., and Sohrabi, A. (2024). Development of phage-containing hydrogel for treating Enterococcus faecalis-infected wounds. PLoS ONE, 19.10.1371/journal.pone.0312469 ↗
19. Arabpour, Z., Abedi, F., Salehi, M., Baharnoori, S.M., Soleimani, M., and Djalilian, A.R. (2024). Hydrogel-Based Skin Regeneration. Int. J. Mol. Sci., 25.10.3390/ijms25041982 ↗
20. Dual cross-linked organic-inorganic hybrid hydrogels accelerate diabetic skin wound healing10.1016/j.cej.2021.129335 ↗
21. Polyurethane based hybrid ciprofloxacin-releasing wound dressings designed for skin engineering purpose10.1016/j.advms.2022.05.003 ↗
22. Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties
23. Advancing burn wound treatment: Exploring hydrogel as a transdermal drug delivery system10.1080/10717544.2023.2300945 ↗
24. Functional hydrogel-based wound dressings: A review on biocompatibility and therapeutic efficacy10.1016/j.lfs.2023.122232 ↗
25. Progress in Hydrogels for Skin Wound Repair10.1002/mabi.202100475 ↗
26. A versatile chitosan nanogel capable of generating AgNPs in-situ and long-acting slow-release of Ag+ for highly efficient antibacterial10.1016/j.carbpol.2021.117636 ↗
27. Injectable Antibacterial Hydrogel with Asiaticoside-Loaded Liposomes and Ultrafine Silver Nanosilver Particles Promotes Healing of Burn-Infected Wounds10.1002/adhm.202203201 ↗
28. Fabrication of gelatin-based and Zn2+-incorporated composite hydrogel for accelerated infected wound healing10.1016/j.mtbio.2022.100216 ↗
29. Au–Pt nanozyme-based multifunctional hydrogel dressing for diabetic wound healing10.1016/j.bioadv.2022.212869 ↗
30. Construction of multifunctional hydrogel with metal-polyphenol capsules for infected full-thickness skin wound healing
31. An injectable photothermally active antibacterial composite hydroxypropyl chitin hydrogel for promoting the wound healing process through photobiomodulation10.1039/D1TB00724F ↗
32. Recent progress of antibacterial hydrogels in wound dressings10.1016/j.mtbio.2023.100582 ↗
33. Wytyczne postępowania miejscowego w ranach niezakażonych, zagrożonych infekcją oraz zakażonych—przegląd dostępnych substancji przeciwdrobnoustrojowych stosowanych w leczeniu ran. Zalecenia Polskiego Towarzystwa Leczenia Ran10.5114/lr.2020.96820 ↗
34. Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing10.1016/j.actbio.2022.04.041 ↗
35. Preparation and properties of ZnO/sodium alginate bi-layered hydrogel films as novel wound dressings10.1039/C9NJ00402E ↗
36. Influence of different divalent ions cross-linking sodium alginate-polyacrylamide hydrogels on antibacterial properties and wound healing10.1016/j.carbpol.2018.05.078 ↗
37. Sustainable Dual Release of Antibiotic and Growth Factor from pH-Responsive Uniform Alginate Composite Microparticles to Enhance Wound Healing10.1021/acsami.9b04750 ↗
38. Bioinspired Injectable Self-Healing Hydrogel Sealant with Fault-Tolerant and Repeated Thermo-Responsive Adhesion for Sutureless Post-Wound-Closure and Wound Healing10.1007/s40820-022-00928-z ↗
39. Controlled release of silver ions from AgNPs using a hydrogel based on konjac glucomannan and chitosan for infected wounds10.1016/j.ijbiomac.2020.01.221 ↗
40. Targeted pH-responsive chitosan nanogels with Tanshinone IIA for enhancing the antibacterial/anti-biofilm efficacy10.1016/j.ijbiomac.2023.124177 ↗
41. Chlorogenic acid- loaded calcium phosphate chitosan nanogel as biofilm degradative materials10.1016/j.biocel.2019.105566 ↗
42. Chitosan Nanogel Design on Gymnema sylvestre Essential Oils to Inhibit Growth of Candida albicans Biofilm and Investigation of Gene Expression ALS1, ALS310.3311/PPch.12519 ↗
43. Gharaghie, T.P., Beiranvand, S., Shirin, N.J., Elahianfar, Y., Ghahari, S., and Ghahari, S. (2021). Thymol-based Chitosan Nanogels Have Strong Antibacterial and Anti-biofilm Effects on Multidrug-resistant Pathogens. Res. Sq., Available online: https://www.researchsquare.com/article/rs-128664/v3.10.21203/rs.3.rs-128664/v2 ↗
44. A chitosan-based hydrogel containing zinc oxide nanoparticles as a carrier for improving antibacterial activity and controlling the release of antibiotics10.1049/mna2.12172 ↗
45. Honey-based hydrogel: In vitro and comparative In vivo evaluation for burn wound healing10.1038/s41598-017-08771-8 ↗
46. Advanced antifouling and antibacterial hydrogels enabled by controlled thermo-responses of a biocompatible polymer composite10.1039/D2BM01244H ↗
47. Chopra, H., Bibi, S., Kumar, S., Khan, M.S., Kumar, P., and Singh, I. (2022). Preparation and Evaluation of Chitosan/PVA Based Hydrogel Films Loaded with Honey for Wound Healing Application. Gels, 8.10.3390/gels8020111 ↗
48. Fabrication of pomegranate/honey nanofibers for use as antibacterial wound dressings10.1016/j.wndm.2020.100181 ↗
49. Susceptibility of Stingless Bee, Giant Bee and Asian Bee Honeys Incorporated Cellulose Hydrogels in Treating Wound Infection10.11113/mjfas.v17n3.2049 ↗
50. Stingless Bee Honey Incorporated Cellulose Hydrogel/Poly(Lactic-Co-Glycolic Acid) Patch as an Alternative Treatment for Aphthous Stomatitis10.35812/CelluloseChemTechnol.2021.55.48 ↗
51. Green electrospun Manuka honey/silk fibroin fibrous matrices as potential wound dressing10.1016/j.matdes.2017.01.023 ↗
52. Chin, J.D., Zhao, L., Mayberry, T.G., Cowan, B.C., Wakefield, M.R., and Fang, Y. (2023). Photodynamic Therapy, Probiotics, Acetic Acid, and Essential Oil in the Treatment of Chronic Wounds Infected with Pseudomonas aeruginosa. Pharmaceutics, 15.10.3390/pharmaceutics15061721 ↗
53. Antimicrobial photodynamic therapy—what we know and what we don’t10.1080/1040841X.2018.1467876 ↗
54. Contribution of photodynamic therapy in wound healing: A systematic review10.1016/j.pdpdt.2017.12.015 ↗
55. Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers10.1016/j.ccr.2016.06.007 ↗
56. Photodynamic therapy as an alternative to antibiotic therapy for the treatment of infected leg ulcers10.1016/j.pdpdt.2018.05.001 ↗
57. Resistance in antimicrobial photodynamic inactivation of bacteria10.1039/c5pp00037h ↗
58. Porolnik, W., Ratajczak, M., Mackowiak, A., Murias, M., Kucinska, M., and Piskorz, J. (2024). Liposomal Formulations of Novel BODIPY Dimers as Promising Photosensitizers for Antibacterial and Anticancer Treatment. Molecules, 29.10.3390/molecules29225304 ↗
59. Photosensitizer-eluting nanofibers for enhanced photodynamic therapy of wounds: A preclinical study in immunocompromized rats10.1016/j.ijpharm.2017.02.004 ↗
60. Factors pivotal for designing of nanoantimicrobials: An exposition10.1080/1040841X.2017.1313813 ↗
61. 5-aminolevulinic acid photodynamic therapy for chronic wound infection in rats with diabetes10.1016/j.biopha.2024.117132 ↗
62. Enhancing wound healing in recalcitrant leg ulcers with aminolevulinic acid-mediated antimicrobial photodynamic therapy10.1016/j.pdpdt.2020.102149 ↗
63. Algorri, J.F., López-Higuera, J.M., Rodríguez-Cobo, L., and Cobo, A. (2023). Advanced Light Source Technologies for Photodynamic Therapy of Skin Cancer Lesions. Pharmaceutics, 15.10.3390/pharmaceutics15082075 ↗
64. A clinical study of photodynamic therapy for chronic skin ulcers in lower limbs infected with Pseudomonas aeruginosa10.1007/s00403-014-1520-4 ↗
65. Efficacy and safety of ALA-PDT in treatment of diabetic foot ulcer with infection10.1016/j.pdpdt.2022.102822 ↗
66. ALA-PDT exerts beneficial effects on chronic venous ulcers by inducing changes in inflammatory microenvironment, especially through increased TGF-beta release: A pilot clinical and translational study10.1016/j.pdpdt.2017.12.012 ↗
67. Open study of photodynamic therapy for skin ulcers infected with MRSA and Pseudomonas aeruginosa10.1016/j.pdpdt.2021.102484 ↗
68. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer10.1111/iju.13291 ↗
69. Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester10.1007/s10103-016-1891-1 ↗
70. Aminoleveulinate photodynamic therapy (ALA-PDT) for Bowen’s disease in a SLE patient: Case report and literature review10.1016/j.pdpdt.2017.01.002 ↗
71. Treatment of chronic wounds with methylene blue photodynamic therapy: A case report10.1016/j.pdpdt.2022.103016 ↗
72. A New Strategy to Destroy Antibiotic Resistant Microorganisms: Antimicrobial Photodynamic Treatment10.2174/138955709788681582 ↗
73. Alves, E., Costa, L., Carvalho, C.M., Tomé, J.P., Faustino, M.A., Neves, M.G., Tomé, A.C., Cavaleiro, J.A., Cunha, A., and Almeida, A. (2009). Charge effect on the photoinactivation of Gram-negative and Gram-positive bacteria by cationic meso-substituted porphyrins. BMC Microbiol., 9, Available online: https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-9-70.10.1186/1471-2180-9-70 ↗
74. New Cationic Liposomes as Vehicles of m-Tetrahydroxyphenylchlorin in Photodynamic Therapy of Infectious Diseases10.1021/mp800037d ↗
75. Treatment of infected wounds with methylene blue photodynamic therapy: An effective and safe treatment method10.1016/j.pdpdt.2020.102051 ↗
76. Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection10.1155/2013/159157 ↗
77. Antimicrobial photodynamic therapy with fulleropyrrolidine: Photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies10.1007/s00253-015-6539-8 ↗
78. Omar, G.S., Wilson, M., and Nair, S.P. (2008). Lethal photosensitization of wound-associated microbes using indocyanine green and near-infrared light. BMC Microbiol., 8, Available online: https://bmcmicrobiol.biomedcentral.com/articles/10.1186/1471-2180-8-111.10.1186/1471-2180-8-111 ↗
79. Evaluation of antimicrobial photodynamic therapy on wounds infected by Staphylococcus aureus in animal models10.1016/j.pdpdt.2020.102092 ↗
80. Photodynamic inactivation of multidrug-resistant Staphylococcus aureus by chlorin e6 and red light (λ = 670 nm)10.1016/j.jphotobiol.2016.07.007 ↗
81. Antimicrobial and anticancer photodynamic activity of a phthalocyanine photosensitizer with N -methyl morpholiniumethoxy substituents in non-peripheral positions10.1016/j.jinorgbio.2017.04.009 ↗
82. Multicationic ruthenium phthalocyanines as photosensitizers for photodynamic inactivation of multiresistant microbes10.1016/j.ejmech.2024.117214 ↗
83. Overview of cationic phthalocyanines for effective photoinactivation of pathogenic microorganisms10.1016/j.jphotochemrev.2021.100422 ↗
84. Correction: Cationic phthalocyanine dendrimers as potential antimicrobial photosensitisers10.1039/C8OB90013B ↗
85. Szczolko, W., Ratajczak, M., Koczorowski, T., Kaminska, D., Goslinski, T., and Dlugaszewska, J. (2022). Promising Photocytotoxicity of Water-Soluble Phtalocyanine against Planktonic and Biofilm Pseudomonas aeruginosa Isolates from Lower Respiratory Tract and Chronic Wounds. Appl. Sci., 12.10.3390/app12083707 ↗
86. Ziental, D., Mlynarczyk, D.T., Kolasinski, E., Güzel, E., Dlugaszewska, J., Popenda, Ł., Jurga, S., Goslinski, T., and Sobotta, L. (2022). Zinc(II), Palladium(II), and Metal-Free Phthalocyanines Bearing Nipagin-Functionalized Substituents against Candida auris and Selected Multidrug-Resistant Microbes. Pharmaceutics, 14.10.3390/pharmaceutics14081686 ↗
87. Lv, H., Liu, J., Wang, Y., Xia, X., Li, Y., Hou, W., Li, F., Guo, L., and Li, X. (2022). Upconversion nanoparticles and its based photodynamic therapy for antibacterial applications: A state-of-the-art review. Front. Chem., 10, Available online: https://www.frontiersin.org/articles/10.3389/fchem.2022.996264/full.10.3389/fchem.2022.996264 ↗
88. Antimicrobial photodynamic and wound healing activity of curcumin encapsulated in silica nanoparticles10.1016/j.pdpdt.2019.101639 ↗
89. Antibiotic-free nanotherapeutics: Hypericin nanoparticles thereof for improved in vitro and in vivo antimicrobial photodynamic therapy and wound healing10.1016/j.ijpharm.2013.06.067 ↗
90. Synergistic in vitro effects of indocyanine green and ethylenediamine tetraacetate-mediated antimicrobial photodynamic therapy combined with antibiotics for resistant bacterial biofilms in diabetic foot infection10.1016/j.pdpdt.2019.01.010 ↗
91. Synergistic gentamicin-photodynamic therapy against resistant bacteria in burn wound infections10.1016/j.pdpdt.2022.103034 ↗
92. Synergistic antimicrobial effect of photodynamic therapy and ciprofloxacin10.1016/j.jphotobiol.2016.02.036 ↗
93. Antibacterial Photodynamic Gold Nanoparticles for Skin Infection10.1021/acsabm.0c01505 ↗
94. The role of topical probiotics on wound healing: A review of animal and human studies10.1111/iwj.13451 ↗
95. Antimicrobial peptides activity in the skin10.1111/srt.12626 ↗
96. Therapeutic utility of antibacterial peptides in wound healing10.1586/14787210.2015.1033402 ↗
97. In vitro interaction of chronic wound bacteria in biofilms10.12968/jowc.2011.20.12.569 ↗
98. Microbiology of the skin and the role of biofilms in infection10.1111/j.1742-481X.2011.00836.x ↗
99. Bădăluță, V.A., Curuțiu, C., Dițu, L.M., Holban, A.M., and Lazăr, V. (2024). Probiotics in Wound Healing. Int. J. Mol. Sci., 25.10.3390/ijms25115723 ↗
100. Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature10.1155/2019/7585486 ↗