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Current standards insufficiently acknowledge the influence of the wound micro-environment on the efficacy of antimicrobial agents. To address this, octenidine/phenoxyethanol, polyhexanide, povidone-iodine, and sodium-hypochloride/hypochlorous acid solutions were submitted to standard-based (DIN-EN-13727) or modified peptide-based challenges and compared to a simulated clinical reference using human acute or chronic wound exudate (AWF/CWF). Antimicrobial efficacy against S. aureus and P. aeruginosa was compared using a quantitative suspension method. Agreement between methods were investigated using Bland-Altman (B&A) analysis. Different substances and challenges demonstrated diverging results, depending on class and concentration of agent and challenge. Highly concentrated antiseptics maintained a high efficacy under complex challenges, while especially chlorine-based irrigation solutions showed a remarkably reduced antimicrobial effect. Composition of challenge substance proved more relevant than pure concentration. Therefore, the current standard challenge conditions did not adequately reflect the wound micro-environment with over- or under-estimating antimicrobial efficacy, whilst the modified peptide-challenge showed a higher level of agreement with simulated realistic conditions (AWF/CWF). The results emphasize that a “one-fits-all” approach is not feasible to generalize antimicrobial efficacy, as certain aspects of the complex micro-environment pose a differing influence on varying agents. Based on these results, revision and target focused adaptation of the current standards should be considered.

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If a wound progressively heals or the healing process is impaired is basically influenced by the surrounding milieu. This is reflected by the wound fluid. Its specific composition triggers the migration, proliferation and differentiation of dermal and epidermal cells which so far was not sufficiently examined in 2D cell culture models. The influence of the different wound entities was analyzed on a newly implemented three dimensional in-vitro model, which improved the transferability to the in-vivo situation. The influence of pooled wound fluids from patients suffering from acute or chronic wounds were investigated within a time period of 10 days after wound application. Histological and immunohistochemical analyses were performed addressing the impact of AWF and CWF on regeneration, such as cell proliferation, fibroblast activity and cell migration. AWF slightly stimulated fibroblast migration while CWF inhibited their activation and migration. The CXCR4-immunopositive population was continuously decreased compared to the control and AWF treatment.The expression of FAP was enhanced under AWF and medium. In keratinocytes CWF massively stimulated cell proliferation initiating on day six after injury. The presence of 10% CWF inhibited fibroblast activation and migration and induced the degradation of the collagen matrix. Keratinocytes were stimulated to proliferate, resulting in healing inhibiting hyperplasia. Transferred to human wounds, no effective wound closure would be achieved because of the de-regulation of pro-proliferative and migration-stimulating factors and a degraded extracellular matrix.This newly implemented 3D study model represents a novel appropriate in-vitro system for studying healing mechanisms and potential therapeutic applications.

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Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.

Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low. Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing. Methods: Five antihypertensive drugs from different substance classes (metoprolol, amlodipine, ramipril, hydrochlorothiazide, candesartan) were investigated, in terms of possible impacts on cell metabolism and migration of human skin fibroblasts and keratinocytes. Additionally, histological and immunohistochemical analyses were performed in a 3-dimensional (3D) wound model addressing the influence on regeneration processes, such as cell migration, metabolic activity, apoptosis and epidermal thickness. Results: Hydrochlorothiazide and ramipril exerted inhibiting effects in nearly all analyses, interestingly, in serum equivalent doses. In contrast, candesartan and amlodipine induced slight positive effects in 2D as well as in 3D models. The previously described positive effects of β-blockers could only partially be confirmed by metoprolol. Antihypertensive drugs affected fibroblasts more than keratinocytes – whether positively or negatively. Conclusion: Antihypertensive drugs have an influence on keratinocytes and fibroblasts; they are not neutral. Candesartan has the most positive effects on skin cells. For angiotensin-converting enzyme inhibitors and thiazide diuretics, wound healing in a 3D model is delayed. β-Receptor blockers seem to improve wound healing to a small extent just like calcium channel blockers. These results should be evaluated in a clinical trial to verify their clinical relevance.

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