| 1. |
- Hartman, Erik, et al.
(författare)
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Bioinformatic Analysis of the Wound Peptidome Reveals Potential Biomarkers and Antimicrobial Peptides
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Wound infection is a common and serious medical condition with an unmet need for improved diagnostic tools. A peptidomic approach, aided by mass spectrometry and bioinformatics, could provide novel means of identifying new peptide biomarkers for wound healing and infection assessment. Wound fluid is suitable for peptidomic analysis since it is both intimately tied to the wound environment and is readily available. In this study we investigate the peptidomes of wound fluids derived from surgical drainages following mastectomy and from wound dressings following facial skin grafting. By applying sorting algorithms and open source third party software to peptidomic label free tandem mass spectrometry data we provide an unbiased general methodology for analyzing and differentiating between peptidomes. We show that the wound fluid peptidomes of patients are highly individualized. However, differences emerge when grouping the patients depending on wound type. Furthermore, the abundance of peptides originating from documented antimicrobial regions of hemoglobin in infected wounds may contribute to an antimicrobial wound environment, as determined by in silico analysis. We validate our findings by compiling literature on peptide biomarkers and peptides of physiological significance and cross checking the results against our dataset, demonstrating that well-documented peptides of immunological significance are abundant in infected wounds, and originate from certain distinct regions in proteins such as hemoglobin and fibrinogen. Ultimately, we have demonstrated the power using sorting algorithms and open source software to help yield insights and visualize peptidomic data.
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| 2. |
- Lundgren, Sigrid, et al.
(författare)
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Analysis of bacteria, inflammation, and exudation in epidermal suction blister wounds reveals dynamic changes during wound healing
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The skin microbiome undergoes dynamic changes during different phases of wound healing, however the role of bacteria in the wound healing process remains poorly described. In this study, we aimed to determine how wound bacteria develop over time in epidermal wounds, and how they interact with inflammatory processes during wound healing. To this end, we analyzed wound fluid and swab samples collected from epidermal suction blister wounds in healthy volunteers. We found that bacterial numbers, measured in swabs and dressing fluid, increased rapidly after wounding and stabilized by day 8. The composition of bacterial species identified by MALDI-TOF mass spectrometry differed between wounds, but generally consisted primarily of commensal bacteria and remained largely stable over time. Inflammation and neutrophil activity, measured by quantification of cytokines and neutrophil proteins in dressing fluid, peaked on day 5. Exudation, measured by quantification of protein content in dressings, also peaked at this time and strongly correlated with cytokine and neutrophil protein levels. Inflammation, neutrophil activity, and exudation were not correlated with bacterial counts at any time, indicating that in normally healing wounds, these processes are primarily driven by the host and are independent of colonizing bacteria. Our analysis provides a comprehensive understanding of epidermal wound healing dynamics in the host and the role of the microbiome in healthy wound healing.Competing Interest StatementA.S. is a founder of in2cure AB, a parent company of Xinnate AB which was the sponsor of the clinical trial from which the biobank samples used in this study are derived. G.P. is employed part-time (20%) by Xinnate AB. The other authors have declared that no conflict of interest exists.Clinical TrialNCT05378997Funding StatementThis study was funded by grants from the Swedish Research Council (project 2017-02341, 2020-02016), Edvard Welanders Stiftelse and Finsenstiftelsen (Hudfonden), the Royal Physiographic Society, the Crafoord and Österlund Foundations, and the Swedish Government Funds for Clinical Research (ALF).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Swedish ethical review authority (etikprövningsmyndigheten) gave ethical approval for this work (application number 2022-00527-01).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe data that support the findings of this study are openly available in Zenodo at http://doi.org/10.5281/zenodo.10283373, reference number 10283373.BCAbicinchoninic acidCFUcolony forming unitsELISAenzyme-linked immunosorbent assayHBPheparin-binding proteinIFNinterferonILinterleukinMALDI-TOFMatrix Assisted Laser Desorption lonization -Time Of FlightMBTMALDI BiotyperMPOmyeloperoxidaseMSmass spectrometryNEneutrophil elastasePBSphosphate-buffered salineTCPthrombin-derived C-terminal peptideTNFtumor necrosis factor
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| 3. |
- Lundgren, Sigrid, et al.
(författare)
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Study protocol for a phase 1, randomised, double-blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics of ascending topical doses of TCP-25 applied to epidermal suction blister wounds in healthy male and female volunteers
- 2023
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction TCP-25 gel is intended for use in treatment of wound infection and inflammation. Current local therapies for wounds have limited efficacy to prevent infections and there are no wound treatments available today that target the excessive inflammation that often hampers wound healing in both acute and chronic wounds. There is therefore a high medical need for new therapeutic alternatives. Methods and analysis A randomised, double-blinded, first-in-human study was designed to evaluate the safety, tolerability and potential systemic exposure of three increasing doses of the TCP-25 gel applied topically on suction blister wounds in healthy adults. The dose-escalation will be divided into three sequential dose groups with eight subjects in each group (24 patients in total). Within each dose group, the subjects will receive four wounds, with two wounds on each thigh. Each subject will receive TCP-25 on one wound per thigh and placebo on one wound per thigh in a randomised double-blinded manner, with a reverse reciprocal position on each respective thigh, to a total of five doses over 8 days. An internal safety review committee will monitor emerging safety and plasma concentration data over the course of the study and must give a favourable recommendation prior to initiating the next dose group, which will receive placebo gel or a higher concentration of TCP-25 in exactly the same manner described above. Ethics and dissemination The study will be performed in accordance with ethical principles consistent with the Declaration of Helsinki, ICH/GCPE6 (R2), European Union Clinical Trials Directive and applicable local regulatory requirements. This study is approved by the Swedish Medical Products Agency and the Swedish ethics committee under the registration number 2022-00527-01. The results of this study will be disseminated via publication to a peer-reviewed journal at the discretion of the Sponsor. Trial registration number NCT05378997.
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| 4. |
- Wallblom, Karl, et al.
(författare)
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Bactogram : Spatial Analysis of Bacterial Colonization in Epidermal Wounds
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Skin barrier damage and subsequent development of harmful microbiota contribute to conditions such as wound infections, atopic dermatitis, and chronic wounds, which impact millions of people globally and pose a significant economic burden on healthcare systems. Established microbial sampling methods, such as swabs and tissue biopsies, provide limited information on the spatial distribution of bacteria. We here describe a new method that produces a visual map of the distribution of cultivable bacteria, denoted “Bactogram”, across the whole wound and surrounding skin, suitable for image-based quantification. As part of an exploratory endpoint in a clinical trial (NCT05378997) we applied the Bactogram method to 48 suction blister wounds in 24 healthy volunteers. Bacteria developed in all wounds, predominantly on the skin under the dressing and near wound edges. Two quantification methods, based on visual scoring and image analysis, demonstrated high inter-, and intra-rater agreement and were used to characterize bacterial re-colonization during epidermal wound healing. We also demonstrated proof of concept that the method can be used with chromogenic agar to enable spatial identification of pathogenic bacterial species, such as Staphylococcus aureus. In conclusion, this study introduces a simple method for sampling bacteria over large areas and generating a bacterial map that can identify spatial variations in bacterial composition and abundance in skin and wound conditions.Competing Interest StatementA.S. is a founder of in2cure AB, a parent company of Xinnate AB, companies that are developing therapies based on thrombin-derived peptides and variants. G.P. is employed part-time (20%) by Xinnate AB. The other authors have declared that no conflict of interest exists.Clinical TrialNCT05378997Clinical Protocols https://doi.org/10.1136/bmjopen-2022-064866 Funding StatementThe exploratory data presented here was supported by grants from the Swedish Research Council (project 2017-02341, 2020-02016), Edvard Welanders Stiftelse and Finsenstiftelsen (Hudfonden), the Royal Physiographic Society, the Crafoord and Österlund Foundations, and the Swedish Government Funds for Clinical Research (ALF). Xinnate AB provided the project management resources and expertise for the regulatory development enabling the clinical parts of the Safety study that generated the control samples used in this work.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Etikprövningsmyndigheten (Swedish Ethics committee) gave ethical approval for this work.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe generated pictures of the Bactograms will be available on reasonable request, after the publication of the treated wound data in a separate publication, since the original images inevitably include both treated and untreated wounds. The code used for the ImageJ macros can be found in Supplementary Data 3. The Python code for creating spatial heat maps can be found in Supplementary Data 4. The complete score data from both the visual scoring and the computer-assisted method is provided in Supplementary Data 5. Further information or instructions required to reanalyze the data reported in this paper are available from the lead contact upon reasonable request.
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| 5. |
- Wallblom, Karl, et al.
(författare)
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Image-based non-invasive assessment of suction blister wounds for clinical safety and efficacy
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Ingår i: Wound Repair and Regeneration. - 1067-1927.
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Tidskriftsartikel (refereegranskat)abstract
- Recognising the need for objective imaging-based technologies to assess wound healing in clinical studies, the suction blister wound model offers an easily accessible wound model that creates reproducible epidermal wounds that heal without scarring. This study provides a comprehensive methodology for implementing and evaluating photography-based imaging techniques utilising the suction blister wound model. Our method encompasses a protocol for capturing consistent, high-quality photographs and procedures for quantifying these images via a visual wound healing score and a computer-assisted colour analysis of wound exudation and wound redness. We employed this methodology on 16 suction blister wounds used as controls in a clinical phase-1 trial. Our method enabled us to discern and quantify subtle differences between individual wounds concerning healing progress, erythema and wound exudation. The wound healing score exhibited a high inter-rater agreement. There was a robust correlation between the spectrophotometer-measured erythema index and photography-based wound redness, as well as between dressing protein content and photography-based dressing yellowness. In conclusion, this study equips researchers conducting clinical wound studies with reproducible methods that may support future wound research and aid in the development of new treatments.
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