PAW-Hydrogel for Chronic Wound Healing

Efficacy and Safety of a Carbopol® 940 Hydrogel Functionalized With Plasma-Activated Water (PAW) in the Treatment of Chronic Wounds: A Randomized Controlled Trial

The goal of this randomized controlled trial is to evaluate the efficacy and safety of a novel hydrogel made of Carbopol® 940 functionalized with Plasma-Activated Water (PAW) in patients with chronic wounds (diabetic foot ulcers, pressure injuries, dehiscent wounds, arterial and venous ulcers). The main questions it aims to answer are:

• Does PAW-hydrogel accelerate wound closure (reduction in surface area) compared to standard advanced wound care?
• Does PAW-hydrogel reduce bacterial load in the wound bed?
• Is PAW-hydrogel safe and well-tolerated (local adverse events, pain)?

Participants will be randomly assigned to one of two groups:

• Experimental group: Topical application of PAW-hydrogel (Carbopol® 940 neutralized to pH 5.5, loaded with reactive oxygen and nitrogen species from plasma activation) 2-3 times per week.
• Control group: Standard advanced wound care (cleaning, debridement, conventional dressings).

Wound area (planimetry), bacterial load (semi-quantitative cultures), pain (Visual Analog Scale), tissue quality (Bates-Jensen scale), and adverse events will be assessed over a 12-week follow-up period.

Study Overview

• Status: Recruiting
• Conditions: Venous Leg Ulcer; Chronic Wound; Wound Dehiscence; Arterial Ulcer; Diabetic Foot Ulcer (DFU); Pressure Ulcer (PU)
• Intervention / Treatment: Device: PAW-Functionalized Carbopol® 940 Hydrogel; Other: Standard Advanced Wound Care

Detailed Description

This prospective, randomized, controlled, parallel-group trial will be conducted at the Wound Clinic and hospitalization services of the Centro Médico ISSEMYM Lic. Arturo Montiel Rojas (Metepec, State of Mexico, Mexico), in collaboration with the Instituto Nacional de Investigaciones Nucleares (ININ), which develops and characterizes the Plasma-Activated Water (PAW) and the functionalized hydrogel.

Adult patients (≥18 years) with chronic wounds of various etiologies - diabetic foot ulcers (Wagner grade 1-2), pressure injuries (grade I-III), dehiscent surgical wounds, venous ulcers, or arterial ulcers - that have failed to heal for more than 3 months and have a surface area between 2 cm² and 20 cm² will be screened. Eligible patients will be randomly allocated (1:1) to either the experimental group (PAW-hydrogel) or the active comparator group (standard advanced wound care). Randomization will be performed using a computer-generated sequence with opaque sealed envelopes.

The PAW-hydrogel intervention consists of a 1% w/v Carbopol® 940 hydrogel neutralized to pH 5.5 and functionalized with PAW generated by a dielectric barrier discharge (DBD) coaxial reactor. The hydrogel is produced under aseptic conditions at ININ, and each batch is tested for pH (5.5) and sterility before release. In the experimental arm, after standard wound cleaning with sterile saline, a uniform layer (3-5 mm thickness) of PAW-hydrogel is applied to cover the entire wound bed, followed by a sterile secondary occlusive dressing. The hydrogel is reapplied 2-3 times per week depending on exudate levels (more frequent for heavily exuding wounds). The control arm receives standard advanced wound care according to ISSEMYM protocols, which includes cleaning, mechanical debridement if needed, and application of conventional dressings (e.g., alginate, foam, or silver-based dressings as clinically indicated), without PAW-hydrogel.

The study is conducted in full compliance with the Declaration of Helsinki and Mexican health regulations (Ley General de Salud). The protocol, informed consent form, and all patient-facing materials have been approved by the Health Research and Research Ethics Committee of ISSEMYM (314/26). All participants provide written informed consent prior to any study procedure. Participants may withdraw at any time without affecting their medical care at ISSEMYM. Data confidentiality is ensured by coding patient identifiers.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Régulo López-Callejas, PhD; Phone Number: 12239 +52 5553297200; Email: regulo.lopez@inin.gob.mx

Study Locations

• Mexico
  • State of Mexico
    • Ocoyoacac, State of Mexico, Mexico, 52750
      • Recruiting
      • Plasma Physics Laboratory, National Institute of Nuclear Research
      • Contact: Diego Medina-Castro, PhD; Phone Number: 12230 +52 5553297200; Email: diego.medina@inin.gob.mx

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults ≥ 18 years of age.
• Diagnosis of chronic wound (diabetic foot ulcer Wagner grade 1-2, pressure injury grade I-III, dehiscent surgical wound, venous or arterial ulcer) with duration > 3 months.
• Wound surface area between 2 cm² and 20 cm².
• For diabetic patients: HbA1c < 9% (stable metabolic control).
• Able and willing to provide written informed consent.

Exclusion Criteria:

• Clinical or radiological evidence of osteomyelitis (Wagner grade > 3).
• Severe arterial insufficiency (ankle-brachial index < 0.5).
• Use of systemic corticosteroids or immunosuppressants.
• Pregnancy or lactation.
• Known autoimmune skin disease (e.g., pemphigus, epidermolysis bullosa).
• Active malignancy or undergoing chemotherapy/radiotherapy.
• Participation in another interventional clinical trial within 30 days prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PAW-Hydrogel; Participants randomized to this arm will receive topical application of the investigational product: a Carbopol® 940 hydrogel (1% w/v) neutralized to pH 5.5 and functionalized with Plasma-Activated Water (PAW) containing stabilized reactive oxygen and nitrogen species (RONS). At each wound care session (2-3 times per week), the wound bed is first cleaned with sterile saline. A uniform layer of PAW-hydrogel is then applied to cover the entire wound surface, followed by a sterile secondary occlusive dressing. The hydrogel remains in place until the next scheduled dressing change. Treatment continues for up to 12 weeks or until complete wound closure, whichever occurs first.	Device: PAW-Functionalized Carbopol® 940 Hydrogel; Topical application of a 1% w/v Carbopol® 940 hydrogel neutralized to pH 5.5, functionalized with Plasma-Activated Water (PAW) containing stabilized reactive oxygen and nitrogen species (RONS, including H₂O₂, O₃, NO₂-, NO₃-). A uniform layer (3-5 mm thick) is applied to the entire wound bed after saline cleaning, covered with a sterile secondary dressing. Frequency: 2-3 times per week depending on exudate level.
Active Comparator: Standard Advanced Wound Care; Participants randomized to this arm will receive the institution's current standard advanced wound care protocol for chronic wounds, as routinely practiced at the Centro Médico ISSEMYM Wound Clinic. At each wound care session (2-3 times per week, consistent with the experimental arm), the wound bed is first cleaned with sterile saline, followed by mechanical debridement of devitalized tissue if clinically indicated by the treating clinician. Subsequently, a conventional advanced dressing is selected according to wound characteristics (exudate level, presence of infection, and tissue type) and applied to cover the wound bed, followed by a sterile secondary dressing. The dressing is changed at each scheduled visit. All participants also receive standard concomitant care as per institutional protocols.	Other: Standard Advanced Wound Care; Conventional advanced wound care following institutional protocol, including wound cleaning with saline, mechanical debridement, and application of standard dressings (e.g., alginate, foam, or silver dressings as clinically indicated). No PAW-hydrogel is used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Wound Area Reduction	Change in wound surface area (mm²) per week, calculated from digital planimetry (ImageJ) of standardized photographs. Unit of measure: mm²/week.	From baseline to week 12, measured weekly.
Change in Bacterial Load	Reduction in semi-quantitative colony forming units (CFU) from wound bed swabs or tissue cultures. Unit of measure: CFU/g or semi-quantitative score.	Baseline, week 4, week 8, and week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Complete Wound Closure	Number of days required for complete re-epithelialization (100% closure, no drainage). Unit of Measure: Days	Up to 12 weeks
Change in Pain Intensity	Patient-reported pain using a Visual Analog Scale (VAS, 0-10, where 0 = no pain and 10 = worst imaginable pain). Unit of Measure: Unit of Measure: 0-10 VAS score.	Baseline, each treatment visit (up to 3 times per week), and at week 12.
Change in Wound Tissue Quality	Assessment using the Bates-Jensen Wound Assessment Tool (or similar), evaluating granulation tissue, necrotic tissue, exudate, and surrounding skin. Unit of Measure: Total score.	Baseline, week 2, week 4, week 8, and week 12.
Incidence of Treatment-Related Adverse Events	Number of participants with local adverse events (erythema, edema, pruritus, persistent pain) assessed by clinical examination and patient report. Unit of measure: Number of participants.	From first application up to week 12.
Number of Dressing Changes Required	Total number of wound care sessions (dressing changes) needed per participant. Unit of measure: Count.	From baseline to complete healing or up to 12 weeks.

Collaborators and Investigators

• Sponsor: Benjamín Gonzalo Rodríguez Méndez
• Collaborators: Centro Medico Issemym

Publications and helpful links

General Publications

• Armstrong DG, Tan TW, Boulton AJM, Bus SA. Diabetic Foot Ulcers: A Review. JAMA. 2023 Jul 3;330(1):62-75. doi: 10.1001/jama.2023.10578.
• Cuellar-Gaona CG, et al. Potent antimicrobial activity of chitosan hydrogels: effects of plasma-activated water and carvacrol. Polym Eng Sci. 2026;66(3):1775-1785.
• Shen AZ, Taha M, Ghannoum M, Tyring SK. Biofilms and Chronic Wounds: Pathogenesis and Treatment Options. J Clin Med. 2025 Nov 2;14(21):7784. doi: 10.3390/jcm14217784.
• Graves N, Phillips CJ, Harding K. A narrative review of the epidemiology and economics of chronic wounds. Br J Dermatol. 2022;187(2):141-148
• McCarty SM, Percival SL. Proteases and Delayed Wound Healing. Adv Wound Care (New Rochelle). 2013 Oct;2(8):438-447. doi: 10.1089/wound.2012.0370.

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Wound Healing; Diabetic Foot; Hydrogel; Chronic Wounds; Plasma-Activated Water; PAW; RONS
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Varicose Veins; Leg Ulcer; Diabetic Neuropathies; Foot Ulcer; Skin and Connective Tissue Diseases; Varicose Ulcer; Diabetic Foot; Pressure Ulcer
• Other Study ID Numbers: UEeIM: 314/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No