Image-based non-invasive assessment of suction blister wounds for clinical safety and efficacy.

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.

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.

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.

Bioinformatic Analysis of the Wound Peptidome Reveals Potential Biomarkers and Antimicrobial Peptides.

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.