Wound Healing Society

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Effects Of Noncontact Low Frequencyultrasound (nlfu) On Wound Healing At The Molecular Level
Cornelia Wiegand1, Kyle Bittenger2, Robert D. Galiano3, Vickie R. Driver4, Pamela G. Unger5, Helen D. Hahn5, Gary W. Gibbons6.
1University Hospital Jena, Jena, Germany, 2Department of Microbiology, Perelman School of Medicine, Philadelphia, PA, USA, 3Division of Plastic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 4Department of Orthopedic Surgery, Brown University, Providence, RI, USA, 5Alliqua Biomedical, Inc, Langhorne, PA, USA, 6Center for Wound Healing, South Shore Hospital, Weymouth, MA, USA.

Background: Chronic-venous-leg-ulcer (CVLU) healing-rates are less than 70% with standard care resulting in rising costs. New therapies are needed to increase healing-rates and reduce healing times. NLFU* is used to treat various types of chronic wounds including venous, diabetic and pressure ulcers. Aim: Objective for this sub-study of the IN-BALANCE-RCT-VLU-trial was to characterize and compare NLFU*-treatment-group and patients receiving standard-of-care (SOC) for effect of treatment on content/quantity of inflammatory cytokines, fibrinogen and bacteria. Methods: 36 subjects with CVLUs were randomized to receive NLFU*-plus-SOC or SOC-alone. Wound-area-reduction was evaluated weekly. PF4, TGF-beta, and fibrinogen were identified using immunohistochemistry. IL-1beta, TNF-alpha, IL-6, IL-8, and IL-10 were measured by multiplex-immunoassay. PathoGenius for 16S-rRNA-marker-gene-tag-sequencing and qPCRs was used to assess bacteria. Results: Higher wound-area-reduction was observed in NLFU*-group (67.0%) compared to SOC-group (41.6%, p<0.05). Anaerococcus, Peptoniphilus, and Finegoldia had the highest median proportion in samples overall. Bacterial load determined local parameters of ulcer inflammation. Peptoniphilus abundance decreased more with NLFU*-treatment relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Fibrinogen amounts significantly diminished over time by NLFU*-treatment (p<0.05) and IL-8 levels declined. Conclusions: NLFU*-treatment is an effective adjuvant tool for CVLU therapy. Data at cellular level demonstrated that NLFU* improves wound healing by equally inhibiting abundant levels of pro-inflammatory cytokines and reducing overall bacterial burden. *MIST-Therapy-System5.0®, Alliqua™BioMedical


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