An Acid-Oxidising Solution Containing Hypochlorous Acid Reduces Staphylococcus aureus and Improves Bacterial Diversity in Epidermolysis Bullosa Wounds

Xiaolong A. Zhou¹ | Michael B. Burns² | Ziyou Ren¹ | Elise Stagaman² | Stefan J. Green³ | Lok Yiu Ashley Wu³ | Lynna Yang¹ | Stephanie Rangel¹ | Lydia Rabbaa1 | Amy S. Paller¹

¹Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA | ²Department of Biology, Loyola University Chicago, Chicago, Illinois, USA | ³Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, Illinois, USA

Correspondence: Amy S. Paller (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。)

Received: 6 February 2025 | Revised: 6 June 2025 | Accepted: 3 August 2025

Funding: This work was supported by Applied Pharma Research.

Keywords: acid-oxidising solution | epidermolysis bullosa | hypochlorous acid | microbiome | Staphylococcus aureus | wounds

ABSTRACT

Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin fragility and chronic, painful wounds that are highly susceptible to bacterial infection, particularly by Staphylococcus aureus (SA). This study evaluated the efficacy of an acid-oxidising solution containing hypochlorous acid (HOCl) in reducing SA colonisation, promoting wound healing, and restoring a healthier microbiome in EB wounds. In a 12-week open-label pilot study, 15EB patients applied the HOCl-based spray (APR-TD011) daily to chronic wounds for 8weeks, with full-length 16S rRNA sequencing of wound swabs performed before, during, and after treatment. At baseline, 87% of patients were culture-positive for SA, and sequencing revealed that SA had the highest relative abundance (34%), followed by Acinetobacter guillouiae and Pseudomonas poae. SA relative abundance decreased precipitously by Weeks 4 (to 11%) and 8 (primary endpoint; to 10%, p<0.01), and this effect persisted at 4weeks post-treatment (Week 12; to 9.7%), including for methicillin-resistant SA. Concurrently, bacterial diversity increased, and wound sizes dimin ished in correlation with reduced SA levels (r=0.64). Younger patients exhibited greater SA reduction trends. The treatment was well-tolerated, with minimal adverse effects and high patient satisfaction. This study underscores the role of microbial dysbiosis in EB wounds and highlights HOCl-based solutions as a promising therapy to mitigate pathogenic burden and enhance wound.

Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice

Thomas H. Leung,^1,2 Lillian F. Zhang,¹ Jing Wang,¹ Shoucheng Ning,³ Susan J. Knox,³ and Seung K. Kim^1,4,5

¹Department of Developmental Biology, ²Department of Dermatology, ³Department of Radiation Oncology, ⁴Howard Hughes Medical Institute, and ⁵Department of Medicine, Oncology Division, Stanford University School of Medicine, Stanford, California, USA.

Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.

Salvage of Infected Orthopedic Hardware With Intraoperative and Postoperative Hypochlorous Acid Instillations

Eric Clayman, MD; Zackery Beauchamp, BS; Jared Troy, MD

Abstract

Background. Orthopedic hardware infections often require hardware removal or replacement. In some situations, hardware removal is not possible or would require amputation. Thus, a method of in-situ hardware salvage could significantly improve patient outcomes. Hypochlorous acid is a broad-spectrum antimicrobial solution with rapid effectiveness in biofilm impairment. 

Methods. This article presents 2 patients with orthopedic hardware infection. Patient A had recurrent draining sinuses from an intramedullary nail in the femur. The orthopedic surgery team recommended above-knee amputation if hardware salvage was not possible. Patient B had a degloving injury of the right upper extremity with radius and ulna fractures that required revascularization and free flap coverage; when hardware infection developed, hardware removal would have required external fixator placement. In both patients, hypochlorous acid was used intraoperatively during debridement to soak the hardware for 5 minutes. Closed suction drains were placed along the hardware, and postoperative instillations of hypochlorous acid were placed through the drains for 5 minutes 1 to 2 times a day for 4 days for Patient A and 7 days for Patient

Results. On follow-up at 10 months for Patient A and at 9 months for Patient B, there was no evidence of recurrent hardware infection. Hardware was successfully salvaged in both patients.

Conclusions. Hypochlorous acid is an effective and safe topical antimicrobial agent for recurrent infections due to hardware-associated biofilm. Postoperative instillations of 0.025% hypochlorous acid through closed suctions drains may improve hardware salvage rates and optimize

Keywords PhaseOne Hypochlorous Acid Hardware Salvage Infected Hardware Biofilm

Kick-Starting Wound Healing: A Review of Pro-Healing Drugs

Bethany L. Patenall , Kristyn A. Carter and Matthew R. Ramsey *

Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (K.A.C.)

* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。; Tel.: +1-(617)-525-5775

Abstract: Cutaneous wound healing consists of four stages: hemostasis, inflammation, proliferation/repair, and remodeling. While healthy wounds normally heal in four to six weeks, a variety of underlying medical conditions can impair the progression through the stages of wound healing, resulting in the development of chronic, non-healing wounds. Great progress has been made in developing wound dressings and improving surgical techniques, yet challenges remain in finding effective therapeutics that directly promote healing. This review examines the current understanding of the pro-healing effects of targeted pharmaceuticals, re-purposed drugs, natural products, and cell-based therapies on the various cell types present in normal and chronic wounds. Overall, despite several promising studies, there remains only one therapeutic approved by the United States Food and Drug Administration (FDA), Becaplermin, shown to significantly improve wound closure in the clinic. This highlights the need for new approaches aimed at understanding and targeting the underlying mechanisms impeding wound closure and moving the field from the management of chronic wounds towards resolving wounds.

Keywords: chronic wounds; diabetes; wound healing; epithelization; macrophages; biomaterials

Comparative assessment of commercially available wound gels in ex vivo human skin reveals major differences in immune response‑modulatory effects

S.Seiser¹ , D. Cerbu¹ , A. Gallhofer¹ , J. Matiasek² & A. Elbe‑Bürger^1*

Effect of Stabilized Hypochlorous Acid on Re-epithelialization and Bacterial Bioburden in Acute Wounds: A Randomized Controlled Trial in Healthy Volunteers

Ewa A. BURIAN¹, Lubna SABAH¹, Klaus KIRKETERP-MØLLER¹, Glenn GUNDERSEN² and Magnus S. ÅGREN^1,3,4

¹Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, ²SoftOx Solutions AS, Oslo, Norway, ³Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, and ⁴Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark