Micro/Nanobubbles (MNBs) for Treatment of Acute and Chronic Wounds (MNB)

Micro/Nanobubbles (MNBs) and Wound Therapy: A Pilot Study Involving a Novel Oxygen Delivery System for Treatment of Acute and Chronic Wounds

The purpose of this study is to assess the safety and efficacy of Micro/nanobubbles (MNB's) for the healing of acute and chronic wounds.

Study Overview

• Status: Recruiting
• Conditions: Wound Heal; Open Wound
• Intervention / Treatment: Other: 0.9% Normal Saline - Irrigation; Drug: Micro/nanobubble (MNB) - Irrigation; Other: 0.9% Normal Saline - Negative Pressure Wound Therapy with Instillation (NPWTi); Drug: Micro/nanobubble (MNB) - Negative Pressure Wound Therapy with Instillation (NPWTi)

Detailed Description

Oxygen delivery is one of the primary factors in wound healing. Micro/nanobubbles (MNBs) can be used to increase the oxygen dissolved in solution and increase oxygen delivery to a wound. The purpose of this research study is to determine if MNBs applied to a wound improve wound healing.

After being informed about the study and potential risks, all patients will need to provide written informed consent before being included in the study. The characteristics of the wound will be assessed and measurements will be taken before and after treatment. Depending on the patient's wound type, the patient will be treated with MNBs in saline gauze which will be applied to the wound daily (for acute wounds), or MNBs in negative pressure wound therapy with instillation (NPWTi) (for chronic wounds) which will be applied to the wound continuously throughout the day with the wound evaluated and sponge replaced every 3-5 days. This is consistent with the current standard of wound care with gauze or NPWTi. Tissue oxygenation using infrared technology and wound healing will be measured and results collected for analysis.

Participation will last approximately 2-4 weeks or the duration of the inpatient admission. If discharge from the hospital is earlier than 2 weeks, the treatment will be discontinued and results will be submitted for analysis.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Leonardo Alaniz, BBA; Phone Number: 602-318-7118; Email: alanizl1@hs.uci.edu
• Study Contact Backup: Name: Lohrasb R Sayadi, MD; Phone Number: 949-209-7267; Email: rsayadi@uci.edu

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • UCI Medical Center
      • Contact: Leonardo Alaniz, MD; Phone Number: 602-318-7118; Email: alanizl1@hs.uci.edu
      • Contact: Lohrasb R Sayadi, MD; Phone Number: (949) 209-7267; Email: rsayadi@uci.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• are above the age of 18.
• have traumatic, surgical, or chronic wounds.
• have radiotherapy related tissue injury.
• have thermal, chemical, and/or electrical burn injuries.
• have pressure ulcers, diabetic foot ulcers, venous ulcers, arterial ulcers, and/or neuropathic skin ulcers.
• have acute ischemic wounds

Exclusion Criteria:

• have infected wounds.
• have wounds with exposed vital structures such as nerves, arteries, and/or veins.
• have wounds associated with malignancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Acute Wounds - Control; This arm will include patients with acute wounds and will receive standard of care: irrigation with normal saline.	Other: 0.9% Normal Saline - Irrigation; A normal saline solution will be used as an irrigation solution to improve wound oxygenation in ischemic tissue (e.g. ischemic surgical tissue, traumatic wounds, and failing replants). The normal saline solution will be used in wet-to-dry wound care dressings with daily scheduled dressing changes.
Experimental: Acute Wounds - Experimental; This arm will include patients with acute wounds and will receive experimental treatment: irrigation with micro/nanobubbles (MNB's) in normal saline.	Drug: Micro/nanobubble (MNB) - Irrigation; An MNB solution will be used as an irrigation solution to improve wound oxygenation in ischemic tissue (e.g. ischemic surgical tissue, traumatic wounds, and failing replants). The MNB solution will be used in wet-to-dry wound care dressings with daily scheduled dressing changes.
Placebo Comparator: Chronic Wounds - Control; This arm will include patients with chronic wounds and will receive standard of care: negative pressure wound therapy with instillation (NPWTi) using normal saline.	Other: 0.9% Normal Saline - Negative Pressure Wound Therapy with Instillation (NPWTi); NPWTi with normal saline will be applied to the wound with 20-minute instillation periods every 3 hours (standard instillation settings) with dressing changes every 3-5 days.
Experimental: Chronic Wounds - Experimental; This arm will include patients with chronic wounds and will receive experimental treatment: negative pressure wound therapy with instillation (NPWTi) using micro/nanobubbles (MNB's) in normal saline.	Drug: Micro/nanobubble (MNB) - Negative Pressure Wound Therapy with Instillation (NPWTi); NPWTi with MNB will be applied to the wound with 20-minute instillation periods every 3 hours (standard instillation settings) with dressing changes every 3-5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound total oxygen saturation level	Near Infrared Spectroscopy Imaging (NIRS) (KENT SnapShot https://www.kentimaging.com/product/) will be used to assess wound oxygenation saturation levels prior to the MNB or normal saline application. This will provide the investigators with a baseline oxygen saturation measurement. The NIRS KENT SnapShot is an FDA approved non-contact-based imaging modality used to assess wound/tissue oxygenation in the clinical setting and is currently available in the investigators' research laboratory.	2-4 weeks
Wound Size/ Surface Area (cm^2)	Daily photographs taken before initiation of treatment and during treatment.	2-4 weeks
Analysis of wound pH	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups, and a pH strip will be used to measure the pH.	2-4 weeks
Wound oxyhemoglobin concentration level	Near Infrared Spectroscopy Imaging (NIRS) (KENT SnapShot https://www.kentimaging.com/product/) will be used to assess wound oxyhemoglobin concentration levels prior to the MNB or normal saline application. This will provide the investigators with a baseline oxygen tension measurement. The NIRS KENT SnapShot is an FDA approved non-contact-based imaging modality used to assess wound/tissue oxygenation in the clinical setting and is currently available in the investigators' research laboratory.	2-4 weeks
Wound deoxyhemoglobin concentration level	Near Infrared Spectroscopy Imaging (NIRS) (KENT SnapShot https://www.kentimaging.com/product/) will be used to assess wound deoxyhemoglobin concentration levels prior to the MNB or normal saline application. This will provide the investigators with a baseline oxygen tension measurement. The NIRS KENT SnapShot is an FDA approved non-contact-based imaging modality used to assess wound/tissue oxygenation in the clinical setting and is currently available in the investigators' research laboratory.	2-4 weeks
Analysis of wound GM-CSF concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess GM-CSF concentration levels.	2-4 weeks
Analysis of wound interferon concentration levels	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess the following interferon concentration levels: IFN alpha, IFN gamma. *These levels will be reported in the same units of measure.	2-4 weeks
Analysis of wound interleukin (IL) concentration levels	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess the following interleukin concentration levels: IL-1 alpha, IL-1 beta, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A (CTLA-8), IL-18, IL-21, IL-22, IL-23, IL-27, IL-31. *These levels will be reported in the same units of measure.	2-4 weeks
Analysis of wound tumor necrosis factor (TNF) concentration levels	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess the following TNF concentration levels: TNF alpha, TNF beta. *These levels will be reported in the same units of measure.	2-4 weeks
Analysis of wound Eotaxin (CCL11) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess Eotaxin (CCL11) concentration levels.	2-4 weeks
Analysis of wound GRO alpha (CXCL1) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess GRO alpha (CXCL1) concentration levels.	2-4 weeks
Analysis of wound IP-10 (CXCL10) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess IP-10 (CXCL10) concentration levels.	2-4 weeks
Analysis of wound MCP-1 (CCL2) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess MCP-1 (CCL2) concentration levels.	2-4 weeks
Analysis of wound MIP-1 alpha (CCL3) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess MIP-1 alpha (CCL3) concentration levels.	2-4 weeks
Analysis of wound MIP-1 beta (CCL4) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess MIP-1 beta (CCL4) concentration levels.	2-4 weeks
Analysis of wound RANTES (CCL5) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess RANTES (CCL5) concentration levels.	2-4 weeks
Analysis of wound SDF-1 alpha concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess SDF-1 alpha concentration levels.	2-4 weeks
Analysis of wound matrix metalloproteinase 1 (MMP1) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess MMP1 concentration level.	2-4 weeks
Analysis of wound matrix metalloproteinase 8 (MMP8) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess MMP8 concentration level.	2-4 weeks
Analysis of wound matrix metalloproteinase 13 (MMP13) concentration level	With each dressing change, a non-traumatic vidal curette will be used to collect wound exudate in both groups. The proteins will then be extracted by standard methods, and ELISA kits will be used to assess MMP 13 concentration level.	2-4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Length of Stay (LOS)	Days of hospital admission	2-4 weeks
Number of participants that return to the operating room	Qualifying individuals include participants that return to the operating room for a procedure (e.g. surgical debridement) on the same wound being treated by the study investigators.	2-4 weeks
Number of participants readmitted to the hospital for same wound after discharge	Qualifying individuals include participants that are readmitted to the hospital for the same wound that was treated by the study investigators.	4-8 weeks

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Investigators: Principal Investigator: Raj Vyas, MD, University of California, Irvine, Dept. of Plastic Surgery; Vice-Chairman

Publications and helpful links

General Publications

• Tsuge H. Micro- and Nanobubbles: Fundamentals and Applications. Boca Raton: CRC Press; 2014.
• Matiasek J, Djedovic G, Kiehlmann M, Verstappen R, Rieger UM. Negative pressure wound therapy with instillation: effects on healing of category 4 pressure ulcers. Plastic and Aesthetic Research. 2018;5.
• Sayadi LR, Banyard DA, Ziegler ME, Obagi Z, Prussak J, Klopfer MJ, Evans GR, Widgerow AD. Topical oxygen therapy & micro/nanobubbles: a new modality for tissue oxygen delivery. Int Wound J. 2018 Jun;15(3):363-374. doi: 10.1111/iwj.12873. Epub 2018 Jan 5.
• Khan MS, Hwang J, Lee K, Choi Y, Kim K, Koo HJ, Hong JW, Choi J. Oxygen-Carrying Micro/Nanobubbles: Composition, Synthesis Techniques and Potential Prospects in Photo-Triggered Theranostics. Molecules. 2018 Aug 31;23(9):2210. doi: 10.3390/molecules23092210.
• Lalezari S, Lee CJ, Borovikova AA, Banyard DA, Paydar KZ, Wirth GA, Widgerow AD. Deconstructing negative pressure wound therapy. Int Wound J. 2017 Aug;14(4):649-657. doi: 10.1111/iwj.12658. Epub 2016 Sep 29.
• Back DA, Scheuermann-Poley C, Willy C. Recommendations on negative pressure wound therapy with instillation and antimicrobial solutions - when, where and how to use: what does the evidence show? Int Wound J. 2013 Dec;10 Suppl 1(Suppl 1):32-42. doi: 10.1111/iwj.12183.
• Jarbrink K, Ni G, Sonnergren H, Schmidtchen A, Pang C, Bajpai R, Car J. The humanistic and economic burden of chronic wounds: a protocol for a systematic review. Syst Rev. 2017 Jan 24;6(1):15. doi: 10.1186/s13643-016-0400-8.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 27, 2021

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: chronic wounds; acute wounds; MNB solution; MNB; Micro/nanobubbles; Micronanobubbles; negative pressure wound therapy with instillation
• Additional Relevant MeSH Terms: Wounds and Injuries; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Physical Therapy Modalities; Rehabilitation; Drainage; Wound Closure Techniques; Hydrotherapy; Negative-Pressure Wound Therapy; Therapeutic Irrigation
• Other Study ID Numbers: 5901; 154138 (Other Identifier: FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD with other researchers outside this study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No