The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Why chronic wounds will not heal: a novel hypothesis
Abstract
The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.
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Cites
Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA
Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., et al. (1989) · Science · doi:10.1126/science.2475911 · Cited by 7,418
Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms
Donlan, R. M., & Costerton, J. W. (2002) · Clinical Microbiology Reviews · doi:10.1128/cmr.15.2.167-193.2002 · Cited by 6,644
Identification of the Cystic Fibrosis Gene: Genetic Analysis
Kerem, B.-S., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M., & Tsui, L.-C. (1989) · Science · doi:10.1126/science.2570460 · Cited by 4,142
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Yager, D. R., Zhang, L.-Y., Liang, H.-X., Diegelmann, R. F., & Cohen, I. K. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12365637 · Cited by 389
Bacterial colonization and healing of venous leg ulcers
Madsen, S. M., Westh, H., Danielsen, L., & Rosdahl, V. T. (1996) · APMIS · doi:10.1111/j.1699-0463.1996.tb04955.x · Cited by 164 · cited 1×
“aeruginosa also seems to delay or even prevent the healing process.(18) Even now, the biofilm mode of bacterial growth has not yet been satisfactorily identified in chronic wounds; however, the clinical signs are similar”
BackgroundQualitative and quantitative microbiological analysis of sputa of 102 patients with cystic fibrosis
Bauernfeind, A., Hörl, G., Jungwirth, R., Petermüller, C., Przyklenk, B., Weisslein-Pfister, C., Bertele, R. M., & Harms, K. (1987) · Infection · doi:10.1007/bf01644137 · Cited by 150
Cited by
Factors affecting wound healing
Guo, S., & DiPietro, L. A. (2010) · Journal of Dental Research · doi:10.1177/0022034509359125 · Cited by 5,792
Sindrilaru, A., Peters, T., Wieschalka, S., Baican, C., Baican, A., Peter, H., Hainzl, A., Schatz, S., Qi, Y., Schlecht, A., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44490 · Cited by 1,100
Bjarnsholt, T., Alhede, M., Alhede, M., Eickhardt-Sørensen, S. R., Moser, C., Kühl, M., Jensen, P. Ø., & Høiby, N. (2013) · Trends in Microbiology · doi:10.1016/j.tim.2013.06.002 · Cited by 764
Self-citationESCMID∗ guideline for the diagnosis and treatment of biofilm infections 2014
Høiby, N., Bjarnsholt, T., Moser, C., Bassi, G. L., Coenye, T., Donelli, G., Hall-Stoodley, L., Holá, V., Imbert, C., Kirketerp-Møller, K., et al. (2015) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2014.10.024 · Cited by 726
Self-citationDowd, S. E., Wolcott, R. D., Sun, Y., McKeehan, T., Smith, E., & Rhoads, D. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003326 · Cited by 481
Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing
Jakobsen, T. H., van Gennip, M., Phipps, R. K., Shanmugham, M. S., Christensen, L. D., Alhede, M., Skindersoe, M. E., Rasmussen, T. B., Friedrich, K., Uthe, F., et al. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05919-11 · Cited by 458
Self-citationNew approaches for treating staphylococcal biofilm infections
Kiedrowski, M. R., & Horswill, A. R. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06281.x · Cited by 288
Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation
Versey, Z., da Cruz Nizer, W. S., Russell, E., Zigic, S., DeZeeuw, K. G., Marek, J. E., Overhage, J., & Cassol, E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.648554 · Cited by 253
Malic, S., Hill, K. E., Hayes, A., Percival, S. L., Thomas, D. W., & Williams, D. W. (2009) · Microbiology · doi:10.1099/mic.0.028712-0 · Cited by 182
A Comparison of Bacterial Composition in Diabetic Ulcers and Contralateral Intact Skin
Gontcharova, V., Youn, E., Sun, Y., Wolcott, R. D., & Dowd, S. E. (2010) · The Open Microbiology Journal · doi:10.2174/1874285801004010008 · Cited by 156
Magnetic Nanoparticle Targeted Hyperthermia of Cutaneous Staphylococcus aureus Infection
Kim, M.-H., Yamayoshi, I., Mathew, S., Lin, H., Nayfach, J., & Simon, S. I. (2013) · Annals of Biomedical Engineering · doi:10.1007/s10439-012-0698-x · Cited by 135
Carpenter, A. W., Worley, B. V., Slomberg, D. L., & Schoenfisch, M. H. (2012) · Biomacromolecules · doi:10.1021/bm301108x · Cited by 132
Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model
Zhao, G., Usui, M. L., Underwood, R. A., Singh, P. K., James, G. A., Stewart, P. S., Fleckman, P., & Olerud, J. E. (2012) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2012.00793.x · Cited by 127
Current concepts regarding the effect of wound microbial ecology and biofilms on wound healing
Black, C. E., & Costerton, J. W. (2010) · Surgical Clinics of North America · doi:10.1016/j.suc.2010.08.009 · Cited by 99
Gene expression profile and pathogenicity of biofilm-forming Prevotella intermedia strain 17
Yamanaka, T., Furukawa, T., Matsumoto-Mashimo, C., Yamane, K., Sugimori, C., Nambu, T., Mori, N., Nishikawa, H., Walker, C. B., Leung, K.-P., et al. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-11 · Cited by 60
Single cells and bacterial biofilm populations in chronic wound infections
Lichtenberg, M., Kirketerp‐Møller, K., Kvich, L. A., Christensen, M. H., Fritz, B., Jakobsen, T. H., & Bjarnsholt, T. (2024) · APMIS · doi:10.1111/apm.13344 · Cited by 26
Self-citationPNA-Based Fluorescence In Situ Hybridization for Identification of Bacteria in Clinical Samples
Fazli, M., Bjarnsholt, T., Høiby, N., Givskov, M., & Tolker-Nielsen, T. (2014) · Methods in Molecular Biology · doi:10.1007/978-1-4939-1459-3_21 · Cited by 22
Self-citationDesign, synthesis and valued properties of surfactin oversimplified analogues
Lima, T. A., Etchegaray, A., & Machini, M. T. (2020) · Amino Acids · doi:10.1007/s00726-019-02806-2 · Cited by 10
Metadata
- Authors
- Bjarnsholt, T., Kirketerp‐Møller, K., Jensen, P. Ø., Madsen, K. G., Phipps, R., Krogfelt, K., Høiby, N., & Givskov, M.
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2007-10-03
- Volume
- 16
- Issue
- 1
- Pages
- 2-10
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W2145402561
- Cited by
- 886
- References
- 7
- FWCI
- 10.42
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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