Wound healing of experimental equine skin wounds and concurrent microbiota in wound dressings following topical propylene glycol gel treatment.
Abstract: Topical wound treatments rely on carrier formulations with little to no biological impact. The potential for a common vehicle, a propylene glycol (PG) gel, to affect wound healing measures including microbiota is not known. Microbiome characterization, based on next generation sequencing methods is typically performed on tissue or directly obtained wound fluid samples. The utility for primary wound dressings to characterize equine wound microbiota in the context of topical treatments is currently unknown. This investigation reports the topical effect of an 80% PG based gel on wound healing and microbiota in wound dressings. Unassigned: Experiments were performed in six mature horses utilizing a surgical, distal limb wound model, histology of sequential wound biopsies, photographic wound measurements and microbiota profiling via 16s rRNA sequencing of wound dressing samples. Experimental wounds were surveyed for 42 days and either treated (Day 7, 14, 21 and 28; at 0.03 ml/cm2) or unexposed to the PG gel. Wound surface area, relative and absolute microbial abundances, diversity indices and histologic parameters were analyzed in the context of the experimental group (treatment; control) using qualitative or quantitative methods depending on data characteristics. Unassigned: Compared to controls, treatment slowed the wound healing rate (17.17 ± 4.27 vs. 18.56 ± 6.3 mm2/day), delayed the temporal decline of polymorphonucleated cells in wound beds and operational taxonomic units (OTU) in wound dressings and lowered alpha-diversity indices for microbiota in primary wound dressing. Relative abundances of OTUs were in line with those previously reported for equine wounds. Clinical outcomes 42 days post wounding were considered similar irrespective of PG gel exposure. Unassigned: Results highlight the potential for vehicle exposure to alter relevant wound outcome measures, imposing the need for stringent experimental control measures. Primary wound dressings may represent an alternate sample source for characterization of the wound microbiome alleviating the need for additional interventions. Further studies are warranted to contrast the microbiome in wound dressings against that present on wound surfaces to conclude on the validity of this approach.
Copyright © 2023 Labens, Raidal, Borgen-Nielsen, Pyecroft, Pant and De Ridder.
Publication Date: 2023-12-14 PubMed ID: 38155761PubMed Central: PMC10752953DOI: 10.3389/fvets.2023.1294021Google Scholar: Lookup
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- Journal Article
Summary
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The research explores the effects of a propylene glycol (PG) gel, a common component in topical wound treatments, on healing rates and microbiota changes in experimental horses. It was discovered that applying this gel resulted in slightly slower wound healing rates, altered immune cell presence, and significantly influenced the microbiota diversity in the wound dressings.
Research Context
- Topical wound treatments often utilize carrier formulations with minimal biological impact. One such common carrier is a propylene glycol (PG) gel.
- This research sought to understand how PG gel affects measures of wound healing, particularly microbial populations inside the wound dressings utilized on horse wounds.
- Wound microbiome is typically analyzed using next-generation sequencing methods on tissue or wound fluid samples. Here, the researchers evaluated the potential of primary wound dressings to characterize equine wound microbiota in the context of topical treatments.
Research Methodology
- Experiments were conducted on six mature horses using a surgically-created, distal limb wound model. The evaluation relied on histology of sequential wound biopsies, photographic wound measurements, and microbiota profiling based on 16s rRNA sequencing of wound dressing samples.
- The researchers surveyed the experimental wounds for 42 days, either treating them with PG gel or leaving them unexposed. They analyzed wound surface area, relative and absolute microbial abundances, diversity indices, and histologic parameters within the treatment and control groups.
Research Findings
- The study revealed that compared to untreated wounds, PG gel treatment slowed the wound healing rate and delayed the reduction of polymorphonucleated cells in wound beds. The cell type is indicative of an immune response, suggesting that PG gel might prolong the inflammation stage of wound healing.
- Also, PG gel treatment lowered alpha-diversity indices for microbiota in primary wound dressing, implying lesser bacterial diversity compared to untreated wounds. Recognizing this impact is crucial as it may affect the wound healing process and the risk of infection.
- Despite these differences, clinical outcomes 42 days post-wounding seemed similar irrespective of PG gel exposure. This suggests that PG gel’s impact on wound healing and microbiome might be significant during the healing process but might not affect the final outcome.
Research Implications and Future Directions
- The study’s findings emphasize that exposure to seemingly innocuous vehicles like PG gel could alter relevant wound outcome measures. Therefore, robust experimental controls are crucial to accurately evaluate the effect of topical treatments.
- The study’s findings suggest that primary wound dressings could be an alternate sample source for characterizing the wound microbiome, potentially reducing the need for additional interventions.
- Future studies should contrast the microbiome in wound dressings against that on wound surfaces to validate the feasibility and accuracy of this approach.
Cite This Article
APA
Labens R, Raidal S, Borgen-Nielsen C, Pyecroft S, Pant SD, De Ridder T.
(2023).
Wound healing of experimental equine skin wounds and concurrent microbiota in wound dressings following topical propylene glycol gel treatment.
Front Vet Sci, 10, 1294021.
https://doi.org/10.3389/fvets.2023.1294021 Publication
Researcher Affiliations
- School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science, Charles Sturt University, Wagga Wagga, NSW, Australia.
- QBiotics Group Ltd., Yungaburra, QLD, Australia.
- School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science, Charles Sturt University, Wagga Wagga, NSW, Australia.
- School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science, Charles Sturt University, Wagga Wagga, NSW, Australia.
- School of Animal and Veterinary Sciences, Faculty of Sciences, Engineering and Technology, University of Adelaide, Roseworthy, SA, Australia.
- School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science, Charles Sturt University, Wagga Wagga, NSW, Australia.
- Gulbali Institute, Charles Sturt University, Wagga Wagga, NSW, Australia.
- QBiotics Group Ltd., Yungaburra, QLD, Australia.
Conflict of Interest Statement
RL serves as a scientific consultant for QBiotics Group Ltd., for which a salary is received. TDR is an employee of Qbiotics Group Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
This article includes 47 references
- Zmora N, Soffer E, Elinav E. Transforming medicine with the microbiome. Sci Transl Med (2019) 11:eaaw1815.
- Loesche M, Gardner SE, Kalan L, Horwinski J, Zheng Q, Hodkinson BP. Temporal stability in chronic wound microbiota is associated with poor healing. J Invest Dermatol (2017) 137:237–44.
- Dunyach-Remy C, Salipante F, Lavigne JP, Brunaud M, Demattei C, Yahiaoui-Martinez A. Pressure ulcers microbiota dynamics and wound evolution. Sci Rep (2021) 11:18506.
- Tomic-Canic M, Burgess JL, O'Neill KE, Strbo N, Pastar I. Skin microbiota and its interplay with wound healing. Am J Clin Dermatol (2020) 21:36–43.
- Xu Z, Hsia HC. The impact of microbial communities on wound healing: a review. Ann Plast Surg (2018) 81:113–23.
- Kunimitsu M, Kataoka Y, Nakagami G, Weller CD, Sanada H. Factors related to the composition and diversity of wound microbiota investigated using culture-independent molecular methods: a scoping review. Drug Discov Ther (2021) 15:78–86.
- Malone M, Schwarzer S, Radzieta M, Jeffries T, Walsh A, Dickson HG. Effect on total microbial load and community composition with two vs six-week topical Cadexomer iodine for treating chronic biofilm infections in diabetic foot ulcers. Int Wound J (2019) 16:1477–86.
- Kalan L, Zhou M, Labbie M, Willing B. Measuring the microbiome of chronic wounds with use of a topical antimicrobial dressing - a feasibility study. PLoS One (2017) 12:e0187728.
- Malone M, Radzieta M, Schwarzer S, Jensen SO, Lavery LA. Efficacy of a topical concentrated surfactant gel on microbial communities in non-healing diabetic foot ulcers with chronic biofilm infections: a proof-of-concept study. Int Wound J (2021) 18:457–66.
- Wu M, Li Y, Guo D, Kui G, Li B, Deng Y. Microbial diversity of chronic wound and successful Management of Traditional Chinese Medicine. Evid Based Complement Alternat Med (2018) 2018:1–13.
- Ernlund AW, Moffatt LT, Timm CM, Zudock KK, Howser CW, Blount KM. Examining the effect of wound cleansing on the microbiome of venous stasis ulcers. Wound Repair Regen (2021) 29:766–76.
- Kamus LJ, Theoret C, Costa MC. Use of next generation sequencing to investigate the microbiota of experimentally induced wounds and the effect of bandaging in horses. PLoS One (2018) 13:e0206989.
- Kožár M, Hamilton H, Koščová J. Types of wounds and the prevalence of bacterial contamination of wounds in the clinical practice of small animals. Folia Vet (2018) 62:39–47.
- Franklin P, Ladlow J, Su X, Cantacessi C, Grant A, de Vries S. Comparison of culture vs 16S ribosomal RNA sequencing of chronic granulation tissue microbiota in cats and dogs. BSAVA Lib (2016) 2016:540–10.
- Sangiorgio DB, Hilty M, Kaiser-Thom S, Epper PG, Ramseyer AA, Overesch G. The influence of clinical severity and topical antimicrobial treatment on bacteriological culture and the microbiota of equine pastern dermatitis. Vet Dermatol (2021) 32:173–e41.
- Harman RM, Theoret CL, Van de Walle GR. The horse as a model for the study of cutaneous wound healing. Adv Wound Care (2021) 10:381–99.
- European Medicines Agency. Propylene glycol used as an excipient: EMA/CHMP/334655/2013. (2013).
- Fowles JR, Banton MI, Pottenger LH. A toxicological review of the propylene glycols. Crit Rev Toxicol (2013) 43:363–90.
- Inactive ingredients database . (2023). U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/inactive-ingredients-database-download.
- Ponec M, Haverkort M, Soei YL, Kempenaar J, Bodde H. Use of human keratinocyte and fibroblast-cultures for toxicity studies of topically applied compounds. J Pharm Sci (1990) 79:312–6.
- Dart AJ, Cries L, Jeffcott LB, Hodgson DR, Rose RJ. Effects of 25% propylene glycol hydrogel (Solugel) on second intention wound healing in horses. Vet Surg (2002) 31:309–13.
- Travis J, Malone M, Hu H, Baten A, Johani K, Huygens F. The microbiome of diabetic foot ulcers: a comparison of swab and tissue biopsy wound sampling techniques using 16S rRNA gene sequencing. BMC Microbiol (2020) 20:163.
- Zhang J, Kobert K, Flouri T, Stamatakis A. PEAR: a fast and accurate Illumina paired-end reAd mergeR. Bioinformatics (2014) 30:614–20.
- Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK. QIIME allows analysis of high-throughput community sequencing data. Nat Methods (2010) 7:335–6.
- Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics (2010) 26:2460–1.
- Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics (2011) 27:2194–200.
- Cole JR, Wang Q, Fish JA, Chai B, McGarrell DM, Sun Y. Ribosomal database project: data and tools for high throughput rRNA analysis. Nucleic Acids Res (2014) 42:D633–42.
- DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K. Greengenes, a chimerachecked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol (2006) 72:5069–72.
- Vazquez-Baeza Y, Pirrung M, Gonzalez A, Knight R. EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience (2013) 2:16.
- Tóth T, Broström H, Båverud V, Emanuelson U, Bagge E, Karlsson T. Evaluation of LHP® (1% hydrogen peroxide) cream versus petrolatum and untreated controls in open wounds in healthy horses: a randomized, blinded control study. Acta Vet Scand (2011) 53:45.
- O'Shaughnessy-Hunter LC, Yu A, Rousseau JD, Foster RA, Weese JS. Longitudinal study of the cutaneous microbiota of healthy horses. Vet Dermatol (2021) 32:467-e128.
- Jørgensen E, Bay L, Bjarnsholt T, Bundgaard L, Sørensen M, Jacobsen S. The occurrence of biofilm in an equine experimental wound model of healing by secondary intention. Vet Microbiol (2017) 204:90–5.
- Berman JJ. Bacteroidetes and Fusobacteria. (2012).
- Kennedy R, Lappin DF, Dixon PM, Buijs MJ, Zaura E, Crielaard W. The microbiome associated with equine periodontitis and oral health. Vet Res (2016) 47:1–9.
- Brook I. Microbiology and management of human and animal bite wound infections. Prim Care (2003) 30:25–39.
- Costa MC, Arroyo LG, Allen-Vercoe E, Stämpfli HR, Kim PT, Sturgeon A. Comparison of the fecal microbiota of healthy horses and horses with colitis by high throughput sequencing of the V3-V5 region of the 16S rRNA gene. PLoS One (2012) 7:e41484.
- Rodriguez C, Taminiau B, Brévers B, Avesani V, Van Broeck J, Leroux A. Faecal microbiota characterisation of horses using 16 rdna barcoded pyrosequencing, and carriage rate of clostridium difficile at hospital admission. BMC Microbiol (2015) 15:181.
- Racklyeft D, Love D. Bacterial infection of the lower respiratory tract in 34 horses. Aust Vet J (2000) 78:549–59.
- Staton GJ, Sullivan LE, Blowey RW, Carter SD, Evans NJ. Surveying bovine digital dermatitis and non-healing bovine foot lesions for the presence of Fusobacterium necrophorum, Porphyromonas endodontalis and Treponema pallidum. Vet Rec (2020) 186:450–10.
- Caddey B, Orsel K, Naushad S, Derakhshani H, De Buck J. Identification and quantification of bovine digital dermatitis-associated microbiota across lesion stages in feedlot beef cattle. mSystems (2021) 6:e00708–21.
- Gardner SE, Hillis SL, Heilmann K, Segre JA, Grice EA. The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes (2013) 62:923–30.
- Malone M, Johani K, Jensen SO, Gosbell IB, Dickson HG, Hu H. Next generation DNA sequencing of tissues from infected diabetic foot ulcers. EBioMedicine (2017) 21:142–9.
- Kaiser-Thom S, Hilty M, Axiak S, Gerber V. The skin microbiota in equine pastern dermatitis: a case-control study of horses in Switzerland. Vet Dermatol (2021) 32:646-e172.
- Sloan TJ, Turton JC, Tyson J, Musgrove A, Fleming VM, Lister MM. Examining diabetic heel ulcers through an ecological lens: microbial community dynamics associated with healing and infection. J Med Microbiol (2019) 68:230–40.
- Weigelt MA, McNamara SA, Sanchez D, Hirt PA, Kirsner RS. Evidence-based review of Antibiofilm agents for wound care. Adv Wound Care (2021) 10:13–23.
- Westgate SJ, Percival SL, Knottenbelt DC, Clegg PD, Cochrane CA. Microbiology of equine wounds and evidence of bacterial biofilms. Vet Microbiol (2011) 150:152–9.
- Sparks HD, Sigaeva T, Tarraf S, Mandla S, Pope H, Hee O. Biomechanics of wound healing in an equine limb model: effect of location and treatment with a peptide-modified collagen-chitosan hydrogel. ACS Biomater Sci Eng (2021) 7:265–78.
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